High-temperature beverages and foods and esophageal cancer risk—A systematic review

Authors

  • Farhad Islami,

    1. Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
    2. Lifestyle, Environment and Cancer Group, International Agency for Research on Cancer, Lyon, France
    3. King's College London, Thames Cancer Registry, London, United Kingdom
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  • Paolo Boffetta,

    1. Lifestyle, Environment and Cancer Group, International Agency for Research on Cancer, Lyon, France
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  • Jian-Song Ren,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Leah Pedoeim,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Dara Khatib,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Farin Kamangar

    Corresponding author
    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
    • Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3034, Bethesda, MD 20892-7232, USA
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    • Fax: +301-496-6829.


Abstract

Coffee, tea and maté may cause esophageal cancer (EC) by causing thermal injury to the esophageal mucosa. If so, the risk of EC attributable to thermal injury could be large in populations in which these beverages are commonly consumed. In addition, these drinks may cause or prevent EC via their chemical constituents. Therefore, a large number of epidemiologic studies have investigated the association of an indicator of amount or temperature of use of these drinks or other hot foods and beverages with risk of EC. We conducted a systematic review of these studies and report the results for amount and temperature of use separately. By searching PubMed and the ISI, we found 59 eligible studies. For coffee and tea, there was little evidence for an association between amount of use and EC risk; however, the majority of studies showed an increased risk of EC associated with higher drinking temperature which was statistically significant in most of them. For maté drinking, the number of studies was limited, but they consistently showed that EC risk increased with both amount consumed and temperature, and these 2 were independent risk factors. For other hot foods and drinks, over half of the studies showed statistically significant increased risks of EC associated with higher temperature of intake. Overall, the available results strongly suggest that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data and results should be reported by histological subtypes of EC. © 2009 UICC

Recurrent thermal injury to the esophageal mucosa due to consumption of large amounts of hot drinks has long been suspected to be a risk factor for esophageal cancer (EC). In 1939, Watson, after reviewing clinical records from 771 EC cases, wrote: “thermal irritation is probably the most constant factor predisposing to the cancer of the esophagus.”1 If hot drinks indeed cause EC, they can explain a large proportion of all cases in populations in which drinking tea, coffee or maté (an herbal infusion of Ilex paraguariensis, commonly consumed in several South American countries) or eating hot foods are common. Nevertheless, the association of hot drinks with EC has been questioned based on both biologic reasons and empirical evidence.

It has been argued that the temperature of hot foods and drinks may fall rapidly in the mouth and oropharynx so that it cannot cause thermal injury to the esophageal mucosa.2 To test this hypothesis, De Jong et al. measured intraesophageal temperature after consumption of hot drinks. The results of their study showed that drinking hot beverages could substantially increase the intraesophageal temperature and this increase was a function of the initial drinking temperature and, more importantly, the size of the sip.3 For example, drinking 65°C coffee increased the intraesophageal temperature by 6–12°C, depending on the sip size.3

Tea, coffee and maté may affect cancer risk not only through thermal effects but also via their chemical constituents. Although some studies have shown mutagenic effects for tea, coffee and unprocessed maté herb (Ilex paraguariensis) extracts,4–10 a number of more recent experimental studies in animals have reported cancer preventive activities for these beverages (reviewed in Refs. 11–15). A number of epidemiological studies have investigated a possible effect of these beverages on cancer risk. With respect to gastrointestinal cancers, recent meta-analyses did not find any significant association between tea drinking and gastric and colorectal cancers,16–18 but coffee drinking was shown to be inversely associated with risk of liver cancer.19, 20

In 1990, a working group of the International Agency for Research on Cancer concluded that there was no sufficient evidence to recognize tea, coffee or maté, in toto, as risk factors of human cancer, but they found that drinking hot maté was a probable risk factor in humans.21 The strongest evidence was for an association with EC. Since then, a large number of additional studies have investigated the association of the beverages and EC. We conducted a systematic review of the results of epidemiologic studies on the association of tea, coffee or maté drinking or of high-temperature food consumption with EC.

Material and methods

We conducted a comprehensive search of the PubMed and ISI-Web of Knowledge databases for all case–control or cohort studies published in English language on the association of tea, coffee, maté or other hot drinks or high-temperature foods and risk of EC. All results were updated on January 23, 2009. The following terms were used in the PubMed Database search: (esophag* or oesophag*) and (cancer or carcinoma or adenocarcinoma or neoplasm or neoplasia or neoplastic) and (tea or mate or coffee or beverage); the search was repeated by replacing the last phrase with (liquid or drinks or alcohol or food) and (hot or cold or warm or temperature). The same terms were used to search text words in the ISI Database. In addition, references cited in the identified articles were searched manually. Two of the authors (F.I. and F.K.) reviewed the search results to reduce the possibility of missing the published papers.

Using the aforementioned approach, a total of 536 articles were retrieved. Figure 1 shows a summary of the article selection process. After reading the abstracts of the retrieved articles, we excluded 417 articles because they were not case–control or cohort studies of hot drinks and EC; the excluded articles were reviews, animal studies, in vitro studies, case series, studies of cancers other than EC or studies of treatment and complications of EC. In case of any doubt, we also reviewed the full texts of these articles. After reviewing the full texts of the remaining 119 articles, we excluded another 57 because they did not present data on the variables of interest, but we found an additional 14 articles by searching the references of the articles. We also included a study which was in press at the time of our review.22 Therefore, a total of 77 relevant articles were found. Of these, 7 articles23–29 were excluded because they reported data on EC in combination with other cancers and an additional 10 publications30–39 were excluded because their results were reported in other publications or in combined analyses. One more study that referred to drinking of hot Calvados,40 a strong spirit which is a well-established cause of EC, was excluded because separating the effect of temperature from that of the spirit per se would be difficult. Finally, a total of 59 full-text articles were included in this systematic review.22, 41–98

Figure 1.

A summary of the search process. *Using 2 search phrases (see text), the retrieved articles were 343 and 95 from PubMed and 243 and 76 from ISI databases. The numbers presented in the diagram are obtained after considering the repeated articles in the 2 searches as a single article. **After considering the repeated articles in the 2 databases as a single article.

Tea, coffee and maté constitute the 3 major types of hot drinks consumed around the world. Therefore, we present data for each one of these, as well as for the mixed group of other hot foods and drinks, in separate tables. The 2 main variables of interest were (i) an indicator of amount consumed (frequency per day, amount per day, duration of use or a composite variable indicating cumulative use) and (ii) temperature.

The etiological factors responsible for the 2 main histological of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), may be different, and any role of hot drinks and foods might be more relevant for ESCC etiology.99 Therefore, where data are available, we present the results for ESCC and EAC separately.

Where both crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported in the paper, we presented the adjusted results. A small number of studies showed crude numbers but not ORs and 95% CIs, in which case we calculated these statistics using simple logistic regression models and presented them. Throughout the article, p values of <0.05 were considered as statistically significant.

Results

Tea

After excluding duplicate publications, we found 38 papers, published between 1974 and 2008, that reported on the association of tea drinking with EC (Table I). These included 33 individual case–control studies, 2 pooled analyses (one combining 5 and one combining 2 case-control studies), and 3 prospective studies. The studies were conducted in the United States, South America, Europe, South Africa, Middle East and South and East Asia, and included both high-risk and low-risk regions. Two of the prospective studies were from Japan and 1 was from China. There were large differences in study size, but the majority of the studies had between 100 and 400 EC cases. Whereas some studies described the type of tea consumed (e.g., green tea or black tea), the large majority did not report on tea type; however, black tea represents the predominant type of tea traditionally drunk in most regions outside East Asia.21

Table I. A Summary of Studies on the Association Between Tea Consumption and Risk of Esophageal Cancer
Reference (Country; period of study)Case/control1Amount, frequency, duration or status of tea drinkingOR/RR/HR (95% CI)2Tea drinking temperatureOR/RR/HR (95% CI)2Comments3
  • EAC, esophageal adenocarcinoma; EC, esophageal cancer; ESCC, esophageal squamous cell carcinoma; HR, hazard ratio; M4, 5-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone (a metabolite of epigallocatechin); M6, 5-(3′,4′-trihydroxyphenyl)-γ-valerolactone (a metabolite of epicatechin); NR, not reported; NS/NR, nonsignificant/not reported (when the exact OR or 95% CI was not reported but the association was reported as nonsignificant); OR, odds ratio; RR, relative risk; 95% CI, 95% confidence interval.

  • 1

    Number of cases and controls in case–control or prospective studies or number of person-years of follow-up in cohort studies, if it is indicated.

  • 2

    If studies reported both crude and adjusted ORs (95% CIs), we only present the adjusted results.

  • 3

    (1) Study design; (2) histological subtypes of EC, if available; (3) matching criteria, if applicable; and (4) the adjustments in statistical models that were done for the presented results.

  • *

    These studies showed crude numbers but not ORs and 95% CIs; we calculated these statistics using simple logistic regression models and present them.

  • Time interval between pouring tea into a cup and drinking it.

De Jong et al.41 (Singapore; 1970–1972)131/665 (95/465 men and 36/200 women)Tea drinking frequency   
  • 1Hospital-based case–control study
  • 2EC was confirmed histologically in 82% of cases; all were ESCC
  • 3Controls were individually matched for age and sex
  • 4Results were adjusted for dialect group
Men: Men 
 Not daily1 Other1
 Daily0.99 (NS/NR) Burning hot2.96 (p < 0.01)
Women: Women: 
 Not daily1 Other1
 Daily0.82 (NS/NR) Burning hot2.28 (NS/NR)
 Cook-Mozaffari et al.42 (Iran; 1975–1976)344/688 (217/434 men and 127/254 women)Tea drinking amountNS/NRMen: 
  • 1Population-based case–control study
  • 2EC was mainly diagnosed on the basis of clinical symptoms, radiological signs and results of the follow-up study. EC was confirmed histologically in 4% of cases
  • 3Controls were individually matched for age, sex and place of residence and, in high-incidence areas, based on the first language of the subjects
  • 4The matched results were adjusted for several socioeconomic indicators (e.g., education), fruit and vegetable intake and tobacco use
 Other1
 Hot tea1.72 (p < 0.01)
Women: 
 Other1
 Hot tea2.17 (p < 0.01)
 Van Rensburg et al.43 (South Africa; 1978–1981)211/211Tea with milk drinking amountNS/NR
  • 1Hospital-based case–control study
  • 2EC diagnosis method was not reported
  • 3Controls were individually matched for age and urban–rural background
  • 4Results came from stepwise multivariate analyses (with adjustment for age effects), which included tobacco and alcohol use and some SES indicators[Note: the frequency of tea with milk drinking was associated with increased risk of EC (p = 0.01) in crude analyses]
 Notani and Jayant44 (India; 1976–1984)236/392Tea drinking frequency 
  • 1Case–control study with only male participants; hospital-based cases, 215 hospital-based and 177 population-based controls
  • 2EC diagnosis method was not reported
  • 3No other matching was reported
  • 4Results were adjusted for age and tobacco use
Versus hospital controls: 
 ≤2 cups/day1
 2+ cups/day1.18 (0.8–1.8)
Versus population controls: 
 ≤2 cups/day1
 2+ cups/day2.39 (1.5–3.9)
Yu et al.45 (United States; 1975–1981)275/275Tea drinking frequency and the manner of drinking (sipped or gulped)NS/NRTemperatureNS/NR
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC (88% ESCC, 8% EAC, 4% unspecified carcinoma)
  • 3Controls were individually matched for age, sex, race and neighborhood
  • 4Multivariate analyses were used in the study; details of the adjustments for tea drinking variables were not reported
Brown et al.46 (United States; 1982–1984 for incidence series, 1977–1981 for mortality series)207/422Tea drinking amount (both regular tea and local herbal tea)NS/NRTemperatureNS/NR
  • 1The study participants were recruited with 2 methods: a hospital-based case–control study (incidence series) and a population-based case–control study with the outcome of EC death (mortality series)
  • 2All cases in the incidence series were histologically confirmed EC (85% ESCC, 13% EAC, 2% carcinosarcoma); similar detailed information on histology was not ascertained for the cases in the mortality series
  • 3Controls were individually matched for age, race, hospital for incidence series and age, race, county of residence and year of death for mortality series
  • 4Results were adjusted for tobacco and alcohol use
Graham et al.47 (United States; 1975–1986)178/174Tea drinking frequency 
  • 1Case–control study; hospital-based cases, population-based controls
  • 2All cases were histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and neighborhood
  • 4Results were adjusted for age, sex, education and tobacco and alcohol use
Nil1
1–15 cups/month1.12 (0.60–2.09)
16–28 cups/month1.21 (0.68–2.17)
29–280 cups/month0.76 (0.41–1.41)
La Vecchia et al.48 (Italy; 1983–1990)294/6,147Tea drinking status1
  • 1Hospital-based case–control study (the data were derived from an integrated series of case–control studies based on a network)
  • 2All cases were histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4Results were adjusted for age, sex, area of residence, education, smoking and coffee use
 Nondrinkers1.0 (0.7–1.4)
 Drinkers 
Wang, YP et al.49 (China, Shanxi; 1988–1989)326/396Tea drinking amountNS/NR
  • 1Case–control study; hospital-based cases, population-based controls
  • 2All cases were initially diagnosed by X-ray; 72% of diagnoses in the high-risk area and 83% in the moderate-risk area were confirmed histologically
  • 3Controls were frequency matched on age, sex and residence
  • 4Results were adjusted for age, sex and farm/nonfarm occupation
Memik et al.50* (Turkey; not reported)78/558Tea drinking frequency 
  • 1Hospital-based case–control study
  • 2EC diagnosis method was not reported
  • 3Controls were matched for age
  • 4No adjustment was reported
 0–3 glasses/day1
 4–10 glasses/day0.28 (0.16–0.46)
 11+ glasses/day0.25 (0.11–0.59)
Hu et al.51 (China; 1985–1989)196/392Tea drinking amount 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and area of residence
  • 4The matched results were adjusted for tobacco and alcohol use, income and occupation
 Nil1
 50–1,500 g/year1.2 (0.7–2.1)
 1,501–3,000 g/year1.8 (1.04–3.3)
 3,000+ g/year3.9 (1.7–9.1)
Strength of tea 
 Nondrinkers1
 Weak0.8 (0.3–2.0)
 Medium1.1 (0.6–1.9)
 Strong2.5 (1.4–4.3)
Gao et al.52 (China; cases were ascertained during 1990–1993, controls were ascertained during 1986–1987)902/1,552Green tea See Table IV 
  • 1Population-based case–control study
  • 2EC was confirmed histologically in 81% of cases (of them: 83% ESCC, 7% EAC, 3% other, 7% unspecified)
  • 3Controls were frequency matched to cases with 4 types of GI cancer cases in the original study (in accordance with the age and sex distribution among the cases)
  • 4Results were adjusted for age, education, birthplace and tobacco and alcohol use[Note: In the analyses for men and women, the numbers of cases/controls were 417/654 and 242/658, respectively. In the analyses for never-smoker/never-alcohol drinker men and women, the number of cases/controls were 69/192 and 184/564, respectively]
Amount (men): 
 Non-tea drinker1
 Tea drinker0.80 (0.58–1.09)
  1–199 g/month0.79 (0.53–1.17)
  200+ g/month0.79 (0.56–1.13)
Amount (women): 
 Non-tea drinker1
 Tea drinker0.50 (0.30–0.83)
  1–149 g/month0.77 (0.39–1.53)
  150+ g/month0.34 (0.17–0.69)
Amount × duration (men): 
 Non-tea drinker1
  1–3,499 (g/month × years)0.73 (0.48–1.11)
  3,500+ (g/month × years)0.83 (0.59–1.16)
Amount × duration (women): 
 Non-tea drinker1
  1–3,4990.74 (0.40–1.38)
  3,500+0.29 (0.13–0.65)
Never-smokers/drinkers 
Amount (men): 
 Non-tea drinker1
 Tea drinker0.43 (0.22–0.86)
  1–199 g/month0.33 (0.14–0.80)
  200+ g/month0.62 (0.25–1.54)
Amount (women): 
 Non-tea drinker1
 Tea drinker0.40 (0.20–0.77)
  1–149 g/month0.70 (0.31–1.58)
  150+ g/month0.17 (0.05–0.58)
Amount × duration (men): 
 Non-tea drinker1
  1–3,499 (g/month × years)0.24 (0.08–0.72)
  3,500+ (g/month × years)0.63 (0.29–1.41)
Amount × duration (women): 
 Nondrinker1
  1–3,499 (g/month × years)0.66 (0.32–1.37)
  3,500+ (g/month × years)0.07 (0.01–0.54)
Srivastava et al.53 (India; not reported)75/75Hot1
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC (85% ESCC, 15% EAC)
  • 3No matching was reported
  • 4In the stepwise multivariate analysis, tea temperature variable was dropped out because it did not have any significant association with the risk (in the final model, only vegetable intake and alcohol use had significant associations with the risk)[Note: In the crude analyses, drinking very hot tea vs. hot tea was associated with increased risk of EC (OR= 2.63, 95% CI 1.13–6.19)]
Very hotNS/NR
Inoue et al.54 (Japan; 1990–1995)185/21,128Green tea frequency 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were noncancer outpatients; no matching was reported
  • 4Results were adjusted for age, sex, year and season at hospital-visit, tea and coffee intake, tobacco and alcohol use, regular physical exercise and fruit, rice and beef intake
Rarely1
Occasionally1.02 (0.50–2.10)
 1–3 cups/day1.07 (0.58–2.00)
 4–6 cups/day0.96 (0.50–1.83)
 7+ cups/day1.14 (0.55–2.34)
Black tea frequency 
Rarely1
Occasionally0.44 (0.26–0.74)
Daily1.03 (0.53–2.00)
 Kinjo et al.55 (Japan; 1966–1981)440/220,272Green tea 
  • 1Cohort study; the outcome was EC death within the cohort
  • 2EC diagnosis method was not reported
  • 3Controls were the noncancer cohort members; no matching was reported
  • 4Results were adjusted for age, sex, prefecture, occupation, vegetable intake and tobacco and alcohol use
Non hot1
Hot1.5 (1.1–1.9)
 Gao et al.56 (China, 1995)81/234Tea drinking amount 
  • 1Population-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched to EC and stomach cancer cases for age, sex and neighborhood; for the analysis, the enrolled controls for the 2 types of cancer were combined
  • 4Results were adjusted for age and sex
Nil1
1–199 g/month0.63 (0.28–1.42)
200+ g/month0.42 (0.19–0.95)
Tao et al.57 (China; 1984–1988)71/1,122Tea drinking frequency 
  • 1Population-based case–control within a cohort study with only male participants; the outcome was EC death within the cohort
  • 2EC diagnosis method was not reported
  • 3Controls were the 1% of total noncancer cohort members, stratified by community; no other matching was reported
  • 4Results were adjusted for age, medical history, occupational history, pesticide exposure, lifestyle factors, dietary habits, education and monthly food expenses
<1 cup/day1
1+ cup/day0.70 (0.39–1.25)
Castellsagué et al.58 (Argentina, Brazil, Uruguay, Paraguay; 1985–1992)830/1,779Tea drinking status Cold/warm1
  • 1A pooled analysis of 5 other hospital-based case–control studies35–38; the results from Uruguay came from 2 studies: one from 1985 to 1988,38 and the other was an extension of that study (1989–1992)
  • 2Cases from Argentina, Brazil and Uruguay had histologically confirmed ESCC; in Paraguay, a cytological or radiological diagnosis of EC was acceptable
  • 3Controls were individually matched for age and sex, admission to the same hospital and during the same period as the corresponding case
  • 4Results were adjusted for age group, sex, hospital, residency, education and tobacco and alcohol use
Never-drinker1Hot0.66 (0.35–1.25)
Ever-drinker0.81 (0.62–1.06)Very hot3.73 (1.41–9.89)
Amount:   
 Nondrinker1  
 1–500 ml/day0.90 (0.67–1.20)  
 >500 ml/day0.62 (0.40–0.96)  
Bosetti et al.59 (Italy; 1992–1997)304/743Coffee and tea frequency 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were frequency matched for age, sex, year of interview and area of residence
  • 4Results were adjusted for age, sex, area of residence, education, tobacco and alcohol use and nonalcohol energy
≤7.9 times/week1
8–14.4 times/week0.91 (0.56–1.48)
14.5–20.9 times/week0.82 (0.47–1.43)
21.0–24.9 times/week0.91 (0.57–1.44)
25+ times/week0.71 (0.42–1.19)
Nayar et al.60 (India; 1994–1997)147/140Warm1
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and socioeconomic status
  • 4For tea temperature variable, only crude analysis was done
Hot1.11 (0.62–1.96)
Burning hot1.27 (0.60–2.69)
Cheng et al.61 (England, Scotland; 1993–1996)74/74Tea drinking amount Tea or coffee 
  • 1Population-based case–control study; only female participants
  • 2All cases were histologically confirmed EC; only EAC cases
  • 3Controls were matched for age and general practice
  • 4No adjustment for tea- or coffee-related variables
Never or <1 dcl/day1Warm1
≤6 dcl/day0.83 (0.26–2.63)Hot0.75 (0.32–1.76)
7–11 dcl/day0.95 (0.30–3.08)Very/burning hot0.51 (0.18–1.45)
12+ dcl/day0.49 (0.14–1.72)  
Terry et al.62 (Sweden; 1995–1997)167 ESCC and 189 EAC/815Tea or coffee 
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC (47% ESCC, 53% EAC)
  • 3Controls from the Sweden population register were frequency matched to resemble the age and sex distribution among the cases
  • 4Results were adjusted for age, sex, BMI, socioeconomic status, tobacco and alcohol use, gastroesophageal reflux symptoms, frequency of hot beverage drinking, energy and fruit and vegetable intake
ESCC: 
 None, cold, lukewarm1
 Hot1.0 (0.6–1.6)
 Very hot0.8 (0.4–1.8)
EAC: 
 None, cold, lukewarm1
 Hot0.7 (0.5–1.1)
 Very hot0.6 (0.3–1.3)
Takezaki et al.63 (China; 1995–2000)195/333Tea drinking amount 
  • 1Case–control study; hospital-based cases and population-based controls
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4Adjusted for age, sex and tobacco and alcohol use
0 g/month1
1–149 g/month0.73 (0.44–1.22)
150+ g/month0.64 (0.36–1.15)
Sharp et al.64 (England, Scotland; 1993–1996)159/159Tea drinking amount Tea or coffee 
  • 1Population-based case–control study; only female participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were matched for age and general practice
  • 4Results were adjusted for slimming diet, breakfast, salad, years of smoking, regular use of aspirin, aspirin center and temperature of tea/coffee
Nil or <1 dcl/day1Very/burning hot1
≤6 dcl/day2.33 (0.62–8.86) Hot0.75 (0.38–1.47)
7–11 dcl/day2.99 (0.85–10.56) Warm0.34 (0.13–0.88)
12+ dcl/day3.36 (0.99–11.29)  
Ke et al.65 (China; 1997–2000)1,248/1,248Congou tea 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age, sex and hospital
  • 4Results were adjusted for age, sex, region, occupation, income, tobacco and alcohol use, some dietary items, including fish sauce, pickled vegetable, sowbelly and fruit and vegetable intake[Note: Congou tea is a grade of Chinese black tea]
Nondrinker1
Drinker0.40 (0.28–0.57)
Amount: 
 500 − g/year1
 10,000− g/year0.52 (0.38–0.70)
 20,000− g/year0.44 (0.29–0.67)
 30,000+ g/year0.05 (0.01–0.22)
Hot Congou tea 
Nondrinker1
Drinker0.04 (0.01–0.13)
Amount: 
 500− g/year1
 10,000− g/year0.41 (0.28–0.62)
 20,000− g/year0.57 (0.34–0.97)
 30,000+ g/year0.03 (0.00–0.23)
Sun et al.66 (China; 1986–1998)42/209Urinary tea polyphenols 
  • 1Nested case–control study; only male participants. Urinary level of 4 tea polyphenols was measured
  • 2All cases were histologically confirmed EC (67% ESCC, 5% EAC, 28% other or unspecified)
  • 3Controls were individually matched for age, month and year of sample collection and neighborhood of residence
  • 4The matched results were adjusted for age at starting to smoke and alcohol use; the cutting points for the urinary levels were the median positive values among all control subjects[Note: For subjects with an interval of 4 years or more between sample collection and cancer diagnosis; the ORs (95% CIs) for level of epigallocatechin for gastric cancer and EC combined were 0.52 (0.28–0.97) and 0.58 (0.34–0.98), respectively
Epigallocatechin: 
 Negative1
 Positive0.87 (0.38–2.02)
 ≤0.196 mg/g creatinine0.84 (0.32–2.19)
 >0.196 mg/g creatinine0.91 (0.36–2.31)
Epicatechin: 
 Negative1
 Positive1.22 (0.48–3.10)
 ≤0.311 mg/g creatinine1.32 (0.51–3.45)
 >0.311 mg/g creatinine0.99 (0.32–3.04)
M4: 
 Negative1
 Positive0.91 (0.44–1.89)
 ≤0.220 mg/g creatinine0.96 (0.43–2.15)
 >0.220 mg/g creatinine0.83 (0.32–2.14)
M6: 
 Negative1
 Positive0.79 (0.38–1.66)
 ≤0.448 mg/g creatinine0.90 (0.40–2.01)
 >0.448 mg/g creatinine0.61 (0.22–1.65)
Onuk et al.67 (Turkey; 1999–2000)44/100Not hot1
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4It is not clear in the article but it seems the results were adjusted for tobacco use, fruit, vegetable, coffee and pickle intake and type of bread
Hot8.7 (2.5–30.2)
Gao, et al.68 (China; 1998–2000)141/223Tea drinking amount 
  • 1Population-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and ethnicity
  • 4Results were adjusted for age, sex, tobacco and alcohol use, raw vegetables, pickled vegetables, fruit, meat, soybean products, GSSTT1 and GSTM1
0 g/month1
1+ g/month0.45 (0.26–0.78)
Tavani et al.69 (Italy, Switzerland; 1991–1997)395/1,066Tea drinking frequency 
  • 1A pooled analysis of 2 hospital-based case–control studies; in the articles from the original studies the association between EC and the variables of interest were not reported
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4Results were adjusted for age, sex, study center, education, tobacco and alcohol use and fruit and vegetable intake
<1 cup/day1
1+ cup/day0.9 (0.7–1.2)
Hung et al.70 (Taiwan; 1996–2002)365/532Tea drinking frequency 
  • 1Hospital-based case–control study; only male participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age and hospitalization date
  • 4Results were adjusted for age, education, ethnicity, hospital location, tobacco and alcohol use and areca nut chewing
Age 20–40 years: 
 <1 time/week1
 1–6 times/week1.0 (0.5–1.7)
 7+ times/week0.7 (0.4–1.1)
Age 40+ years: 
 <1 time/week1
 1–6 times/week0.7 (0.4–1.2)
 7+ times/week0.5 (0.3–0.8)
Chitra et al.71 (India; 1999–2000)90/90Tea drinking frequency 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age and sex
  • 4No adjustment was reported
≤3 cups/day1
3+ cups/day3.3 (1.7–6.3)
Yang et al.72 (China; 2003–2004)185/185Tea drinking frequency 
  • 1Case–control study; hospital-based cases and population-based controls
  • 2All cases had histologically confirmed EC; 179 ESCC cases and 6 EAC cases
  • 3Controls were individually matched for age and sex
  • 4The matched results were adjusted for family history of EC, occupation, tobacco and alcohol use, some dietary items, including fruit and vegetable intake, hot food, water supply, eating speed and intake of pickled vegetables, fresh meat, processed meat, eggs and tea
≤1 time/week1
2–4 times/week0.45 (0.15–1.36)
>4 times/week0.57 (0.25–1.31)
Ishikawa et al.73 (Japan; 1984–1992 cohort 1, 1990–1997 cohort 2)78/196,686 person-yearsGreen tea frequencyHR (95% CI)
  • 1Cohort study with only male participants; cases were EC cases within 2 cohorts, controls were noncancer members of the 2 cohorts
  • 2EC diagnosis method was not reported
  • 3No matching was reported
  • 4Results were adjusted for age, tobacco and alcohol use, and coffee and black tea consumption
Never/occasionally1
1–2 cups/day1.03 (0.46–2.28)
3–4 cups/day1.13 (0.53–2.42)
5+ cups/day1.67 (0.89–3.16)
Wang et al.74 (China; 2002–2003)107/107Green tea 
  • 1Population-based case–control study
  • 2Cases were confirmed by endoscopy, X-ray or clinical histopathology
  • 3Controls were individually matched for age, sex and residency
  • 4Matched results were adjusted for family history of cancer, eating fast, utensil clean up, H. pylori infection and esophageal lesions
Nondrinker1
Drinker0.13 (0.03–0.62)
Wang et al.75 (China; 2004–2006)355/408Green tea 
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were group matched for age and sex
  • 4Results were adjusted for age, marital status and education[Note: Cases were enrolled from patients referred to 1 hospital, but they accounted for 85% of all histologically confirmed ECs in the study area during the study period]
Status (men) 
 Nondrinker1
 Drinker1.37 (0.95–1.98)
Status (women) 
 Nondrinker1
 Drinker0.26 (0.07–0.94)
Duration (men) 
 Nil1
 <30 years1.31 (0.85–2.03)
 30+ years1.44 (0.91–2.27)
Duration (women) 
 Nil1
 <30 years0.33 (0.06–1.68)
 30+ years0.18 (0.02–1.54)
Gledovic et al.76 (Serbia; 1998–2002)102/102Tea drinking status 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age, sex and urban–rural residence
  • 4The matched results were adjusted for education, occupational exposure to chemicals, family history of cancer, noncarbonated beverages consumption and tobacco and alcohol use[Note: Tea consumption was inversely associated with increased risk of ESCC in crude analyses]
Nondrinkers1
DrinkersNS/NR
Wu et al.77 (China; 2003–2007)1,520/3,879Green tea Green tea 
  • 1Population-based case–control study
  • 2Cases were confirmed by endoscopy, X-ray or histopathology
  • 3Controls were frequency matched for age, sex and county of residence
  • 4Results were adjusted for age, gender, education level, income 10 years before, family history of cancer, body mass index and tobacco and alcohol use; results for amount of green tea consumed was also adjusted for tea temperature[Note: The number of cases/controls in high- and low-risk areas was 637/1,938 and 883/1,941, respectively]In multivariate models that did not include tea temperature, most of the green tea consumption indicators were associated with increased risk of ESCC
High-risk area High-risk area: 
 Status:  Never drinking1
  Never-drinker1 Normal temperature1.0 (0.7–1.3)
  Ever-drinker1.0 (0.7–1.3) High temperature2.2 (1.6–5.3)
  Former-drinker2.2 (1.6–5.3)Low-risk area: 
  Current-drinker0.8 (0.6–1.1) Never drinking1
 Duration:  Normal temperature1.3 (0.9–1.7)
  Never-drinker1 High temperature4.2 (2.3–7.6)
  <25 years1.0 (0.6–1.4)  
  20–34 years0.9 (0.6–1.4)  
  35+ years1.1 (0.7–1.8)  
 Monthly consumption:   
  Never-drinker1  
  1–149 g1.0 (0.7–1.3)  
  150–249 g1.0 (0.6–1.8)  
  250+ g1.0 (0.6–2.0)  
 Age at tea drinking start:   
  Never-drinker1  
  <25 years0.8 (0.4–1.5)  
  25–34 years1.2 (0.8–1.8)  
  35–44 years1.2 (0.7–1.9)  
  45+ years0.8 (0.6–1.2)  
Low-risk area:   
 Status:   
  Never-drinker1  
  Ever-drinker1.3 (0.9–1.7)  
  Former-drinker4.2 (2.3–7.6)  
  Current-drinker1.1 (0.8–1.5)  
 Duration:   
  Never-drinker1  
  <25 years0.8 (0.5–1.5)  
  20–34 years1.4 (1.0–2.0)  
  35+ years1.1 (0.8–1.6)  
   Monthly consumption:    
  Never-drinker1  
  1–149 g1.1 (0.7–1.7)  
  150–249 g1.0 (0.7–1.6)  
  250+ g1.6 (1.1–2.2)  
 Age at tea drinking start:   
  Never-drinker1  
  <25 years1.2 (0.8–1.9)  
  25–34 years1.3 (1.0–1.9)  
  35–44 years1.1 (0.7–1.8)  
  45+ years0.9 (0.4–1.9)  
Islami et al.22 (Iran; 2003–2007)298/568Black tea Temperature 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age, sex and neighborhood of residence
  • 4The matched results were adjusted for ethnicity, duration of residence in rural areas, education, tobacco or opium use, alcohol use, vegetable intake and owning an automobile; black tea consumption, green tea consumption and tea temperature were also adjusted for each other[Note: Amount of tea consumed was available for 266 cases and 386 controls. The fifth quintile of black tea consumption was significantly associated with increased risk of ESCC in crude analyses (OR = 1.86, 95% CI 1.07–3.23)]
Amount (quintiles): Warm or lukewarm1
 0–675 ml/day1 Hot2.07 (1.28–3.35)
 676–920 ml/day0.91 (0.43–1.91) Very hot8.16 (3.93–16.91)
 921–1,215 ml/day0.68 (0.34–1.37)Time interval 
 1,216–1,725 ml/day1.46 (0.75–2.86)4+ min1
 1,726+ ml/day1.83 (0.93–3.59)2–3 min2.49 (1.62–3.83)
Green tea <2 min5.41 (2.63–11.14)
Frequency:   
 Never, <weekly1  
 Daily, weekly0.86 (0.38–2.09)  

Amount consumed

Most studies (n = 33) provided results for one of the indicators of amount consumed, e.g., amount per day, frequency per day, duration of use or an indicator of cumulative use. However, not all studies reported ORs (95% CIs) or crude numbers. There was no clear pattern of association between amount of tea consumed and EC risk; 7 studies showed an increase in risk (4 were statistically significant), and this was counterbalanced by 15 individual studies and a pooled analysis of 5 case–control studies that showed an inverse association between tea drinking and EC risk, either in the main analyses or in subgroup analyses (the association in 8 studies was statistically significant). Four studies reported ORs close to 1, on both sides of the null line, which were not statistically significant. In addition, 6 other studies only stated that the results were not statistically significant, without reporting detailed results. We did not find a clear pattern of association by geographic region. However, the majority of the inverse associations were from East-Asian countries, especially China, where mostly green tea is used.

Temperature

Results for the association of tea drinking temperature and EC were reported in 14 publications. Of these, 7 individual case–control studies, a combined analysis of 5 other case–control studies and a prospective study found an increased risk; of these, the association was statistically significant in 8 studies. Two case–control studies reported statistically nonsignificant inverse associations, and 3 other studies only stated that the results were not statistically significant, without reporting crude numbers or ORs.

Coffee

We found 22 independent papers, published between 1974 and 2008, that reported on the association between coffee intake and EC (Table II). These included 17 individual case–control studies, 2 pooled analyses (one combining 5 and one combining 2 case-control studies), and 3 cohort studies. Most reports (n = 14) were from the United States or Europe. Most studies included between 100 and 400 EC cases.

Table II. A Summary of Studies on the Association Between Coffee Consumption and Risk of Esophageal Cancer
Reference (Country; period of study)Case/control1Amount, frequency or status of coffee drinkingOR/RR/HR (95% CI)2Coffee drinking temperatureOR/RR/HR (95% CI)2Comments3
  • BMI, body mass index; EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; HR, hazard ratio; NR, not reported; NS/NR, nonsignificant/not reported (when the exact OR or 95% CI was not reported but the association was reported as nonsignificant); OR, odds ratio; RR, relative risk; 95% CI, 95% confidence interval.

  • 1

    Number of cases and controls in case–control or prospective studies or number of person-years of follow-up in cohort studies, if it is indicated.

  • 2

    If studies reported both crude and adjusted ORs (95% CIs), we only present the adjusted results.

  • 3

    (1) Study design; (2) histological subtypes of EC, if available; (3) matching criteria, if applicable; and (4) the adjustments in statistical models were done for the presented results.

  • *

    These studies showed crude numbers but not ORs and 95% CIs; we calculated these statistics using simple logistic regression models and present them.

De Jong et al.41 (Singapore; 1970–1972)131/665Coffee drinking frequency Men: 
  • 1Hospital-based case–control study
  • 2EC was confirmed histologically in 82% of cases; all were ESCC
  • 3Controls were individually matched for age and sex
  • 4Results are adjusted for dialect group
Men:  Other1
 Not daily1 Burning hot4.22 (NR, p < 0.01)
 Daily0.93 (NS/NR)Women: 
Women:  Other1
 Not daily1 Burning hot4.09 (NR, p < 0.01)
 Daily1.42 (NS/NR)  
Jacobsen et al.78 (Norway; 1967–1978)15/See notesCoffee drinking frequency 
  • 1Cohort study with 16,555 participants at baseline
  • 2EC diagnosis method was not reported
  • 3Mortality rates in the cohort were compared with expected rates
  • 4Results for all cases were stratified by sex, age and residence; results for men were stratified for age, residence and smoking[Note: Coffee drinking frequency was categorized as ≤2, 3–4, 5–6 and 7+ cups/day; RR was presented only for 7+ vs. ≤2 cups/day groups, for which the numbers of cases were 3 and 4, respectively (the numbers of male cases were 1 and 1, respectively)]
All: 
 ≤2 cups/day1
 7+ cups/day1.19 (p = 0.85)
Men: 
 ≤2 cups/day1
 7+ cups/day0.79 (p = 0.88)
Yu et al.45 (United States; 1975–1981)275/275Coffee drinking frequency, the manner of drinking (sipped or gulped) and coffee type (caffeinated or decaffeinated)NS/NRTemperatureNS/NR
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC (88% ESCC, 8% EAC, 4% unspecified carcinoma)
  • 3Controls were individually matched for age, sex, race and neighborhood
  • 4Multivariate analyses were used in the study; details of the adjustments for tea drinking variables were not reported
Brown et al.46 (United States; 1982–1984 for incidence series, 1977–1981 for mortality series)207/422Coffee drinking amountNS/NRTemperatureNS/NR
  • 1The study participants were recruited with 2 methods: a hospital-based case–control study (incidence series) and a population-based case–control study with the outcome of EC death (mortality series)
  • 2In the incidence series, all cases were histologically confirmed EC (85% ESCC, 13% EAC, 2% carcinosarcoma); detailed information on histology was not ascertained for the cases in the mortality series
  • 3Controls were individually matched for age, race, hospital and county of residence
  • 4Results were adjusted for study series and tobacco and alcohol use
La Vecchia et al.79 (Italy; 1983–1988)209/1,944Coffee drinking frequency 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4Results were adjusted for age, sex, social class, education, marital status and tobacco and alcohol use
0–1 cup/day1
2 cups/day0.90 (NS)
3+ cups/day0.98 (NS)
Graham et al.47 (United States; 1975–1986)178/174Coffee drinking amountNS/NR
  • 1Case–control study: hospital-based cases and population-based controls
  • 2All cases were histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and neighborhood
  • 4Results are adjusted for age, sex, education and tobacco and alcohol use
Memik et al.50 (Turkey; not reported)78/610Coffee drinking amountNS/NR
  • 1Hospital-based case–control study
  • 2EC diagnosis method was not reported
  • 3Controls were matched for age
  • 4No adjustment was reported
Garidou et al.80 (Greece; 1989–1991)43 ESCC and 56 EAC/200Coffee drinking frequency 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC (43% ESCC, 57% EAC)
  • 3Controls were individually matched for age and sex
  • 4Results are adjusted for age, sex, birthplace, education, height, analgesics, coffee drinking, tobacco and alcohol use and energy intake[Note: The OR values here indicate how much the risk was increased when drinking one more cup per day]
ESCC: 
 1 cup/day more1.15 (0.84–1.58)
EAC: 
 1 cup/day more1.11 (0.86–1.43)
Inoue et al.54 (Japan; 1990–1995)185/21,128Coffee drinking frequency 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were noncancer outpatients; no matching was reported
  • 4Results are adjusted for age, sex, tea and coffee intake, tobacco and alcohol use, regular physical exercise, fruit, rice and beef intake and year and season at first hospital-visit
Rarely1
Occasionally0.82 (0.51–1.31)
1–2 cups/day0.77 (0.52–1.12)
3+ cups/day0.79 (0.46–1.36)
Castellsagué et al.58 (Argentina, Brazil, Uruguay, Paraguay; 1986–1992)830/1,779Coffee drinking Coffee 
  • 1A pooled analysis of 5 other hospital-based case–control studies35–38; the results from Uruguay came from 2 studies: one from 1985 to 1988,38 and the other was an extension of that study (1989–1992)
  • 2Cases from Argentina, Brazil and Uruguay had histologically confirmed ESCC; in Paraguay, a cytological or radiological diagnosis of EC was acceptable
  • 3Controls were individually matched for age and sex, admission to the same hospital and during the same period as the corresponding case
  • 4Results are adjusted for age group, sex, hospital, residency, education and tobacco and alcohol use
Status: Cold/warm1
 Never-drinker1Hot0.54 (0.33–0.87)
 Ever-drinker1.04 (0.83–1.30)Very hot1.01 (0.52–1.98)
Amount:   
 Nondrinker1Coffee with milk 
 1–500 ml/day0.96 (0.74–1.24)Cold/warm 
 >500 ml/day1.26 (0.88–1.81)Hot1
Coffee with milk Very hot0.89 (0.62–1.29)
Status:  2.29 (1.37–3.81)
 Never-drinker1  
 Ever-drinker1.15 (0.94–1.42)  
Amount:   
 Nondrinker1  
 1–500 ml/day1.12 (0.90–1.40)  
 >500 ml/day1.31 (0.89–1.95)  
Bosetti et al.59 (Italy; 1992–1997)304/743Coffee and tea frequency 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were frequency matched for age, sex, year of interview and area of residence
  • 4Results were adjusted for age, sex, area of residence, education, tobacco and alcohol use and nonalcohol energy
≤7.9 times/week1
8–14.4 times/week0.91 (0.56–1.48)
14.5–20.9 times/week0.82 (0.47–1.43)
21.0–24.9 times/week0.91 (0.57–1.44)
25+ times/week0.71 (0.42–1.19)
(quintiles) 
Terry et al.81 (Sweden; 1994–1997)185/815Coffee drinking frequency 
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC; only EAC cases
  • 3Controls from the Sweden population register were frequency matched to resemble the age and sex distribution among the cases
  • 4Results are adjusted for age, sex, BMI, socioeconomic status, tobacco and alcohol use, use of antacids and energy, fruit and vegetable intake
0–2 cups/day1
2–4 cups/day0.8 (0.5–1.4)
4–7 cups/day0.9 (0.5–1.5)
>7 cups/day0.8 (0.5–1.4)
(quartiles) 
Cheng et al.61 (England, Scotland; 1993–1996)74/74Coffee drinking amount Tea or coffee 
  • 1Population-based case–control study; only female participants
  • 2All cases were histologically confirmed EC; only EAC cases
  • 3Controls were matched for age and general practice
  • 4No adjustment for tea- or coffee-related variables
Never or <1 dcl/day1Warm1
≤ 3 dcl/day0.65 (0.27–1.53)Hot0.75 (0.32–1.76)
4–7 dcl/day1.62 (0.53–4.94)Very/burning hot0.51 (0.18–1.45)
8+ dcl/day1.95 (0.68–5.57)  
Terry et al.62 (Sweden; 1995–1997)167 ESCC and 189 EAC/815Tea or coffee ESCC: 
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC (47% ESCC, 53% EAC)
  • 3Controls from the Sweden population register were frequency matched to resemble the age and sex distribution among the cases
  • 4Results were adjusted for age, sex, BMI, socioeconomic status, tobacco and alcohol use, gastroesophageal reflux symptoms, frequency of hot beverage drinking, energy and fruit and vegetable intake
 None, cold, lukewarm1
 Hot1.0 (0.6–1.6)
 Very hot0.8 (0.4–1.8)
EAC: 
 None, cold, lukewarm1
 Hot0.7 (0.5–1.1)
 Very hot0.6 (0.3–1.3)
Sharp et al.64 (England, Scotland; 1993–1996)159/159Tea or coffee 
  • 1Population-based case–control study; only female participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were matched for age and general practice
  • 4Results were adjusted for slimming diet, breakfast, salad, years smoking, regular use of aspirin, aspirin center and temperature of tea/coffee
Very/burning hot1
Hot0.75 (0.38–1.47)
Warm0.34 (0.13–0.88)
Onuk et al.67 (Turkey; 1999–2000)44/100Coffee drinking amount 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4It is not clear in the article but it seems the results were adjusted for tobacco use, fruit, vegetable, coffee and pickle intake and type of bread
Low1
High0.8 (0.3–1.6)
Tavani et al.69 (Italy, Switzerland; 1991–1997)395/1,066Coffee drinking frequency1
  • 1A pooled analysis of 2 hospital-based case–control studies; in the articles from the original studies the association between EC and the variables of interest were not reported
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3No matching was reported
  • 4Results were adjusted for age, sex, study center, education, tobacco and alcohol use and fruit and vegetable intake
≤1 cup/day1.1 (0.8–1.6)
>1–2 cup/day0.9 (0.6–1.3)
>2–3 cup/day0.6 (0.4–0.9)
3+ cup/day 
Decaffeinated coffee1
<1 cup/day0.6 (0.2–1.5)
1+ cup/day 
Hung et al.70 (Taiwan; 1996–2002)365/532Coffee drinking frequency   
  • 1Hospital-based case–control study; only male participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age and hospitalization date
  • 4Results were adjusted for age, education, ethnicity, hospital location, tobacco, alcohol use and areca nut chewing
Age 20–40 years: 
 <1 time/week1
 1+ times/week0.7 (0.4–1.2)
Age 40+ years: 
 <1 time/week1
 1+ times/week0.7 (0.4–1.2)
Ishikawa et al.73 (Japan; 1984–1992 cohort 1, 1990–1997 cohort 2)78/196,686 person-yearsCoffee drinking frequency 
  • 1Cohort study with only male participants; cases were EC cases within 2 cohorts and controls were noncancer members of the 2 cohorts
  • 2EC diagnosis method was not reported
  • 3No matching was reported
  • 4Results were adjusted for age, tobacco and alcohol use and green tea and black tea consumption
Never-drinkers1
1–2 cups/day0.63 (0.32–1.27)
3+ cups/day0.94 (0.36–2.45)
Gledovic et al.76 (Serbia; 1998–2002)102/102Coffee ever drinking and amountNS/NR
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age and sex
  • 4The matched results were adjusted for education, occupational exposure to chemicals, family history of cancer and tobacco and alcohol use[Note: Coffee consumption with frequency of more than 3 cups/day was associated with increased risk of ESCC in crude analyses]
Rossini et al.82* (Brazil; 1995–2000)36/290Coffee drinking frequency 
  • 1Hospital-based case–control study: cases were head and neck cancer cases with second primary ESCC; controls were head and neck cancer cases without second primary ESCC
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3No matching was reported
  • 4No adjustment was reported
<5 times a week1
5+ times a week1.89 (0.43–8.27)
Naganuma et al.83 (Japan; 1990–2003)112/495,138 person-yearsCoffee drinking frequency 
  • 1Cohort study
  • 2EC diagnosis method was not reported
  • 3No matching was reported
  • 4Results were adjusted for age, sex, BMI, tobacco and alcohol use, fruit and vegetable consumption and green tea consumption
Never1
Occasionally0.56 (0.35–0.90)
1+ cup/day0.60 (0.37–0.97)

Amount consumed

Most studies (n = 20) reported on one of the indicators of amount consumed and EC risk. Four case–control studies showed statistically nonsignificant positive associations. Seven studies reported an inverse association between coffee drinking and EC risk, of which only 1 prospective study from Japan and a combined analysis of 2 case–control studies from Italy and Switzerland showed statistically significant results for drinking 3 or more cups per day. Four other studies, including 2 prospective studies, showed nonsignificant results with ORs close to 1, on both sides of null line. The remaining 5 studies only reported that the results were not statistically significant.

Temperature

Six individual case–control studies and a pooled analysis of 5 other case–control studies reported on temperature of coffee consumption in relation to EC risk. Of these, 2 individual studies and the pooled analysis showed an increased risk with drinking hot or very hot coffee, either in the main analyses or in subgroup analyses; 2 studies suggested statistically nonsignificant inverse associations, and 2 other studies only reported that the results were not statistically significant.

Maté

We found 4 independent papers, including 3 individual case–control studies, and a combined analysis of 5 other case–control studies. These reports were published between 1985 and 2008 and all came from South American countries (Table III).

Table III. A Summary of Studies on the Association Between Maté Consumption and Risk of Esophageal Cancer
Reference (Country; period of study)Case/control1Amount, frequency, duration or status of maté drinkingOR (95% CI)2Maté drinking temperatureOR (95% CI)2Comments3
  • EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; OR, odds ratio; RR, relative risk;95% CI, 95% confidence interval.

  • 1

    Number of cases and controls.

  • 2

    If studies reported both crude and adjusted ORs (95% CIs), we only present the adjusted results.

  • 3

    (1) Study design; (2) histological subtypes of EC, if available; (3) matching criteria, if applicable; and (4) the adjustments in statistical models that were done for the presented results.

  • *

    These studies showed crude numbers but not ORs and 95% CIs; we calculated these statistics using simple logistic regression models and present them.

Vassallo et al.84 (Uruguay; 1979–1984)226/469Ever vs. never maté use 
  • 1Hospital-based case–control study; controls were patients with neoplastic conditions
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3No matching was reported
  • 4Results were adjusted for age (results for amount of maté drinking by men were also adjusted for tobacco and alcohol use; a few women were smokers or alcohol drinkers)
Men3.9 (2.0–7.5)
Women11.9 (2.0–69.6)
Maté drinking amount 
Men: 
 Nondrinker1
 0.01–0.49 l/day1.1 (0.2–5.0)
 0.50–0.99 l/day3.1 (1.2–7.8)
 1.0+ l/day4.8 (1.9–12.1)
Women: 
 Nondrinker1
 0.01–0.49 l/day2.1 (0.1–31.7)
 0.50–0.99 l/day12.5 (2.0–80.1)
 1.0+ l/day34.6 (4.9–246.5)
Castellsagué et al.58 (Argentina, Brazil, Uruguay, Paraguay; 1986–1992)830/1,779Maté drinking Cold/warm1
  • 1A pooled analysis of 5 other hospital-based case–control studies35–38; the results from Uruguay came from 2 studies: one from 1985 to 1988,38 and the other was an extension of that study (1989–1992)
  • 2Cases from Argentina, Brazil and Uruguay had histologically confirmed ESCC; in Paraguay, a cytological or radiological diagnosis of EC was acceptable
  • 3Controls were individually matched for age and sex, admission to the same hospital and during the same period as the corresponding case
  • 4Results are adjusted for age group, sex, hospital, residency, education and tobacco and alcohol use
Status: Hot1.11 (0.84–1.47)
 Never-drinker1Very hot1.89 (1.24–2.86)
 Ever-drinker1.52 (1.10–2.12)  
 Ex-drinker1.87 (1.25–2.80)  
 Current-drinker1.47 (1.06–2.05)  
Amount:   
 Nil1  
 0.01–0.50 l/day1.39 (0.98–1.98)  
 0.51–1.00 l/day1.34 (0.95–1.90)  
 1.01–1.50 l/day1.96 (1.27–3.03)  
 1.51–2.00 l/day2.03 (1.32–3.13)  
 >2.00 l/day3.04 (1.84–5.02)  
Duration:   
 Nil1  
 1–29 years1.40 (0.91–2.13)  
 30–39 years1.39 (0.93–2.07)  
 40–49 years1.53 (1.06–2.21)  
 50–59 years1.47 (1.00–2.17)  
 60+ years1.92 (1.25–2.96)  
Amount: cold/hot drinkers:   
 ≤0.50 l/day1  
 0.51–1.00 l/day0.91 (0.71–1.16)  
 1.01–1.50 l/day1.50 (1.05–2.14)  
 1.50+ l/day1.38 (1.00–1.90)  
Amount: very hot drinkers:   
 ≤0.50 l/day0.99 (0.48–2.02)  
 0.51–1.00 l/day1.59 (0.96–2.63)  
 1.01–1.50 l/day0.73 (0.24–2.26)  
 1.50+ l/day4.14 (2.24–7.67)  
Sewram et al.85 (Uruguay; 1988–2000)344/469Maté drinking Nondrinkers1
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were frequency matched by gender
  • 4Results were adjusted for age, sex, urban/rural status, education and tobacco and alcohol use
Status: Warm/hot2.00 (1.05–3.81)
 Never-drinker1Very hot3.98 (1.98–8.44)
 Ever-drinker2.26 (1.19–4.27)  
Lifetime amount:   
 Nil1  
 1–8,000 l-years1.43 (0.68–3.01)  
 8,001–16,000 l-years2.21 (1.12–4.35)  
 16,001–24,000 l-years2.43 (1.22–4.83)  
 24,001+ l-years3.07 (1.53–6.16)  
Duration:   
 Nil1  
 1–35 years1.31 (0.61–2.81)  
 36–49 years2.29 (1.16–4.52)  
 50–58 years2.58 (1.27–5.24)  
 59+ years4.31 (1.99–9.34)  
Daily amount:   
 Nil1  
 0.01–0.50 l1.69 (0.85–3.35)  
 0.51–1.00 l2.47 (1.28–4.77)  
 1.01+ l2.84 (1.41–5.73)  
De Stefani et al.86, 87* (Uruguay; 1996–2004)234/936 for drinking amount; 234/468 for drinking temperatureMaté drinking amount Warm1
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age, sex and residence
  • 4For maté drinking variables, only raw data were presented
Nil1Hot2.03 (1.23–3.34)
0.01–0.99 l/day1.86 (0.93–3.72)Very hot5.76 (2.92–11.35)
1.00–1.99 l/day3.05 (1.59–5.85)  
2.00+ l/day3.30 (1.64–6.62)  

Amount consumed

All reports showed significantly increased EC risk with amount consumed, with ∼3-fold higher risk in those in the highest category of consumption compared with those who did not consume maté. The pooled analysis of the case–control studies found that amount per day and duration of drinking both increased the risk.

Temperature

Three of these publications reported on the association of temperature of maté drinking and EC risk and all showed significant increased risk with increasing temperature. Mutual adjustment for temperature and amount in the pooled analysis suggested that amount and temperature of use were independent risk factors for EC.

High-temperature food or other drinks

We found 19 publications (17 individual case–control studies, a combined analysis of 5 other case–control studies and 1 prospective study) that presented results on the association of consumption of high-temperature food, other drinks or all beverages combined with risk of EC (Table IV). The reports were published between 1974 and 2008, and the studies were conducted in South Americas, Europe, Africa and South and East Asia. For this category, we only presented results on temperature.

Table IV. A Summary of Studies on the Association Between High-Temperature Foods or Drinks (Other than Tea, Coffee and Maté, Unless the Results Have Been Reported as a Combination of them) and Risk of Esophageal Cancer
Reference (Country; period of study)Case/control1Food or drink temperatureOR/RR (95% CI)2Comments3
  • EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; OR, odds ratio; RR, relative risk; 95% CI, 95% confidence interval.

  • 1

    Number of cases and controls.

  • 2

    If studies reported both crude and adjusted ORs (95% CIs), we only present the adjusted results.

  • 3

    (1) Study design; (2) histological subtypes of EC, if available; (3) matching criteria, if applicable; and (4) the adjustments in statistical models that were done for the presented results.

  • *

    These studies showed crude numbers but not ORs and 95% CIs; we calculated these statistics using simple logistic regression models and present them.

De Jong et al.41 (Singapore; 1970–1972)131/665Barely temperature 
  • 1Hospital-based case–control study
  • 2EC was confirmed histologically in 82% of cases; all were ESCC
  • 3Controls were individually matched for age and sex
  • 4Results are adjusted for dialect group
Men: 
 Other1
 Burning hot6.97 (P < 0.01)
Women: 
 Other1
 Burning hot15.28 (P < 0.01)
Astini et al.88* (Ethiopia; 1988–1989)25/50High-temperature food 
  • 1Hospital-based case–control study
  • 2EC was diagnosed on the basis of clinical symptoms and radiological signs
  • 3Controls were individually matched for age, sex and visiting the same hospital at the same time
  • 4In the matched analysis that was presented in the article, the OR (95% CI) could not be calculated (because most cells contained zeros)
Nonuser1
User36.0 (4.5–287.8)
Cheng et al.89, 90 (Hong Kong; 1989–1990)400/1,598 (68 never-smoker and 52 never-drinker/540 never-smoker and 407 never-drinker)Preference for hot drinks or soups 
  • 1Hospital-based case–control study; for each case, 2 controls were selected from the same hospital as the cases; 2 other controls were enrolled from the same clinic from which the cases were originally referred
  • 2All cases were histologically confirmed EC (85% ESCC, 12% EAC and 3% other)
  • 3Controls were individually matched for age and sex
  • 4For all participants, the matched results were adjusted for age, education and birth place; for never-smokers and never-drinkers, the matched results were adjusted for age, sex, education, place of birth, fruit and vegetable intake and tobacco and alcohol use
All participants: 
 No1
 Yes1.64 (1.30–2.08)
Never-smokers: 
 No1
 Yes1.51 (0.80–2.83)
Never-drinkers: 
 No1
 Yes1.76 (0.90–3.45)
Hu et al.51 (China; 1985–1989)196/392Eaten gruel temperature 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and area of residence
  • 4The matched results were adjusted for tobacco and alcohol use, income and occupation
Cold1
Mild1.1 (0.4–3.4)
Hot2.4 (0.9–6.4)
Scalding5.3 (1.4–20.9)
Gao et al.52, 91 (China; 1990–1993)902/1,552Burning hot fluids 
  • 1Population-based case–control study
  • 2EC was confirmed histologically in 81% of cases (of them, 83% ESCC, 7% EAC, 3% other and 7% unspecified)
  • 3Controls were frequency matched to cases with 4 types of GI cancer cases in the original study (in accordance with the age and sex distribution among the cases)
  • 4Results for burning hot fluids consumption were adjusted for age, education, birthplace and tobacco and alcohol use; results for soup/porridge temperature were adjusted for age, education, birthplace, tea drinking, tobacco and alcohol use and consumption of preserved foods, vegetables and fruit
Men: 
 No + no green tea drinking1
 Yes + no green tea drinking4.80 (2.85–8.08)
 No + green tea drinking0.88 (0.61–1.29)
 Yes + green tea drinking3.09 (1.94–4.93)
Women: 
 No + no green tea drinking1
 Yes + no green tea drinking4.78 (2.89–7.90)
 No + green tea drinking0.50 (0.27–0.91)
 Yes + green tea drinking2.00 (0.75–5.07)
Soup/porridge 
Men: 
 Cold/lukewarm1
 Hot1.21 (0.88–1.66)
 Burning hot4.75 (3.33–6.79)
Women: 
 Cold/lukewarm1
 Hot1.90 (1.29–2.79)
 Burning hot6.77 (4.09–11.20)
Hanaoka et al.92 (Japan; 1989–1991)141/141High-temperature food and drink 
  • 1Hospital-based case–control study; only male participants; 64% of controls had another malignant neoplasm
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and place of residence
  • 4The matched results were adjusted for alcohol use
 Dislike1
 Indifferent2.06 (0.94–4.52)
 Like2.99 (1.18–7.55)
Guo et al.93 (China; 1986–1991)640/3,200Hot liquids 
  • 1Nested case–control study
  • 2EC was diagnosed on the basis of radiological signs, cytology or histology; nearly all cases with a microscopic diagnosis had ESCC
  • 3Controls were individually matched for age and sex
  • 4The matched results were adjusted for cancer history in first degree relatives and smoking
0 time/month1
1+ times/month0.9 (0.7–1.0)
Tran et al.94 (China; 1986–2001)1,958/29,584Hot liquid in summer 
  • 1Cohort study; controls were noncancer members of the cohort (extension of Guo et al. study [reference 93]).
  • 2All cases had histologically confirmed EC; only ESCC cases
  • 3No matching was reported
  • 4Results were adjusted for age and sex
0 time/year1
1+ times/year0.96 (0.87–1.07)
Hot liquid in winter 
0 time/year1
1+ times/year0.95 (0.87–1.04)
Srivastava et al.53 (India; not reported)75/75Food temperature 
  • 1Hospital-based case–control study
  • 2All cases were histologically confirmed EC (85% ESCC, 15% EAC)
  • 3No matching was reported
  • 4In the stepwise multivariate analysis, tea temperature variable was dropped out because it did not have any significant association with the risk (in the final model, only vegetable intake and alcohol use had significant associations with the risk)[Note: Preference for high-temperature food showed a significant association with ESCC risk in the crude analyses]
Warm1
HotNS/NR
Garidou et al.80 (Greece; 1989–1991)43 ESCC and 56 EAC/200Preference for beverage and food 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC (43% ESCC, 57% EAC)
  • 3Controls were individually matched for age and sex
  • 4Results are adjusted for age, sex, birthplace, education, height, analgesics, coffee drinking, tobacco and alcohol use and energy intake
ESCC: 
 Cold to hot1
 Very hot1.89 (0.80–4.49)
EAC: 
 Cold to hot1
 Very hot1.82 (0.85–3.91)
ESCC + EAC: 
 Cold to hot1
 Very hot>1 (NR, P = 0.02)
Castellsagué et al.58 (Argentina, Brazil, Uruguay, Paraguay; 1986–1992)830/1,779Beverage temperature 
  • 1A pooled analysis of 5 other hospital-based case–control studies35–38; the results from Uruguay came from 2 studies: 1 from 1985 to 1988,38 and the other was an extension of that study (1989–1992)
  • 2Cases from Argentina, Brazil and Uruguay had histologically confirmed ESCC; in Paraguay, a cytological or radiological diagnosis of EC was acceptable
  • 3Controls were individually matched for age and sex, admission to the same hospital and during the same period as the corresponding case
  • 4Results are adjusted for age group, sex, hospital, residency, education and tobacco and alcohol use
Any beverage, excluding mate: 
 Never very hot1
 Ever very hot2.45 (1.72–3.49)
Any beverage, including mate: 
 Never very hot1
 Ever very hot2.07 (1.55–2.76)
Nayar et al.60 (India; 1994–1997)150/150Food temperature 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age, sex and socioeconomic status
  • 4For food temperature variable, only crude analysis was done
Warm1
Hot0.68 (NS/NR)
Phukan et al.95 (India; 1997–1998)502/1,004Food temperature 
  • 1Hospital-based case–control study
  • 2All cases had histologically confirmed EC; no information about EC subtypes was reported
  • 3Controls were individually matched for age and sex initially; some cases and controls were dropped later on and the pairing identity was not retained
  • 4Results were adjusted for education, income, chewing betel nut and tobacco and alcohol use[Note: For hot food category, the p value and 95% CI for the OR was reported as <0.05 and 0.6–7.5, respectively. The statement in the text is “ingestion of food at very high temperature emerged as a very significant factor (OR = 6.5) that seemed to persist, although in lower magnitude, even after adjustment for the other variables (OR=2.8)”. Therefore, we considered that association as statistically significant]
Moderate1
Cold1.2 (0.04–4.1)
Hot2.8 (p <0.05)
 [see notes]
Yokoyama et al.96* (Japan; 2000–2001)234/634Preference for high-temperature food (categories: dislike very much, dislike somewhat, neither like nor dislike, like somewhat, like very much)NS/NR
  • 1Hospital-based case–control study; only male participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3No other matching was reported
  • 4Results were adjusted for age and tobacco and alcohol use[Note: Preference for high-temperature food showed a significant association with ESCC risk in the crude analyses]
Hung et al.70 (Taiwan; 1996–2002)365/532Hot drinks or soup 
  • 1Hospital-based case–control study; only male participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were individually matched for age and hospitalization date
  • 4Results were adjusted for age, education, ethnicity, hospital location, tobacco and alcohol use and areca nut chewing
Age 20–40 years: 
 <3 times/week1
 3+ times/week1.8 (1.1–3.0)
Age 40+ years: 
 <3 times/week1
 3+ times/week1.3 (0.8–2.1)
Eating overheated food 
Age 20–40 years: 
 No1
 Yes2.7 (1.6–4.4)
Age 40+ years: 
 No1
 Yes2.1 (1.3–3.4)
Yang et al.72 (China; 2003–2004)185/185Eating high-temperature food 
  • 1Case–control study; hospital-based cases and population-based controls
  • 2All cases had histologically confirmed EC; 179 ESCC cases and 6 EAC cases
  • 3Controls were individually matched for age and sex
  • 4The matched results were adjusted for family history of EC, occupation, tobacco and alcohol use, some dietary items, including fruit and vegetable intake, hot food, water supply, eating speed and intake of pickled vegetables, fresh meat, processed meat, eggs and tea
Rarely1
Occasionally0.43 (0.17–1.09)
Often0.40 (0.14–1.16)
Yokoyama et al.97 (Japan; 2000–2004)52/412Preference for hot food or drinks 
  • 1Hospital-based case–control study; only female participants
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3No other matching was reported
  • 4Results were adjusted for age
Dislike very much1
Dislike somewhat0.21 (0.01–3.60)
Neither like nor dislike1.00 (0.12–8.17)
Like somewhat1.53 (0.18–12.92)
Like very much3.43 (0.39–30.46)
Wu et al.98 (China; 2003–2005)531/531 (291/291 from a high-risk area and 240/240 from a low-risk area)Food temperature 
  • 1Population-based case–control study
  • 2Of all the EC cases in the high-risk area (Dafeng), 46% were histologically confirmed, and 40% and 13% were diagnosed by endoscopy and radiology, respectively; in the low-risk area (Ganyu), 30% of EC cases were histologically confirmed, and 50% and 16% were diagnosed by endoscopy and radiology, respectively
  • 3Controls were individually matched for age and sex
  • 4The matched results were adjusted for education, BMI, tobacco and alcohol use, family history of cancer, eating speed and self-reported grain contamination with fungi
High-risk area: 
 Normal1
 Hot0.51 (0.24–1.09)
Low-risk area: 
 Normal1
 Hot1.14 (0.55–2.41)
Wang et al.75 (China; 2004–2006)355/408 (223/252 men, 132/156 women)Food temperature 
  • 1Population-based case–control study
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3Controls were matched for age and sex
  • 4Results were adjusted for age, marital status and education[Note: Cases were enrolled from patients referred to 1 hospital, but they accounted for 85% of all histologically confirmed ECs in the study area during the study period]
Men: 
 Warm1
 Hot2.13 (1.39–3.25)
Women: 
 Warm1
 Hot3.05 (1.73–5.36)
Rossini et al.82* (Brazil; 1995–2000)36/290Hot drinks 
  • 1Hospital-based case–control study; cases were head and neck cancer cases with second primary ESCC; controls were head and neck cancer cases without second primary ESCC
  • 2All cases were histologically confirmed EC; only ESCC cases
  • 3No matching was reported
  • 4No adjustment was reported
<1 time a week1
1–2 times a week0.69 (0.20–2.41)
3–4 times a week0.71 (0.09–5.75)
5+ times a week1.14 (0.44–2.97)
Food temperature 
Cool1
Warm1.13 (0.27–4.66)
Hot0.98 (0.20–4.82)

Temperature

In all, 11 individual case–control studies and the combined analysis showed positive associations (11 were statistically significant), whereas 2 case–control studies found statistically nonsignificant inverse associations. Two case–control studies and the prospective study reported ORs close to 1, on both sides of null line, with no statistically significant association. Two other studies only stated that the results were not statistically significant, without reporting crude numbers or ORs.

Summary of all hot foods and drinks

A summary of the associations between amount or temperature of consumed tea, coffee or maté, or consumption of high-temperature food or other beverages, and risk of EC is presented in Table V.

Table V. A Summary of the Associations Between Amount or Temperature of Consumed Tea, Coffee or Maté, or Consumption of High-Temperature Food or Other Beverages and Risk of Esophageal Cancer by Study Design
VariableProspectiveCase–controlTotal
NS/NRNS/NR
  • Numbers in parentheses represent statistically significant studies. Associations: ↓, decreased risk; ↑, increased risk; ↔, ORs close to 1 or ORs with no clear trend in 2 sides of null line; NS/NR, there was no statistically significant association but crude numbers or ORs were not reported or ORs for adjusted models cannot be calculated.

  • *

    One of the studies was a pooled analysis of 5 other studies.

  • In two studies, the inverse association was observed only among women.

  • One of the studies was a pooled analysis of 2 other studies.

  • §

    In the pooled analysis of 5 other studies, the positive association was reported for drinking very hot coffee and milk.

  • In the nested control study, an odds ratio (95% confidence interval) of 0.9 (0.7–1.0) was reported. When the cases from an extended study were compared with a subcohort, no significant association was found.

Tea (38 papers)         
 Amount2 (0)1 (0)0014 (8*,)6 (4)4633
 Temperature0 (0)1 (1)002 (0)8 (7*)0314
Coffee (22 papers)         
 Amount1 (1)0 (0)206 (1)4* (0)2520
 Temperature0 (0)0 (0)002 (0)3 (3*,§)027
Maté (4 papers)         
 Amount0 (0)0 (0)0004 (4*)004
 Temperature0 (0)0 (0)0003 (3*)003
Temperature of food or other beverages (19 papers)0 (0)0 (0)102 (0)12 (11*)2219

Discussion

In this systematic review, we collected the published literature on the association between consuming tea, coffee, maté or other high-temperature beverages or foods and risk of EC. We analyzed the results for amount consumed and temperature of drinking separately. For tea and coffee, there was little evidence that the amount consumed was associated with EC risk, but the majority of the publications reported statistically significant increased risks associated with higher temperature of use. For maté, individual studies and combined analyses showed increased risk of EC associated with both amount consumed and temperature of drinking, and these 2 seemed to be independent risk factors. For other hot foods and drinks, the majority of studies showed higher risk of EC associated with higher temperature of use.

There are several limitations to making definitive conclusions about the association of amount or temperature of these drinks with EC risk. Some of these limitations are due to the design of the published studies (retrospective nature of the data, subjective questions, incomplete questionnaires and lack of information on histologic type of EC) and others are due to incomplete analysis or reporting of the data. The large majority of the reports were based on retrospective case–controls studies, so the data might have been subject to interviewer bias or recall bias. This is further complicated by asking subjective questions, such as “how hot do you drink your tea?,” which can be particularly prone to such biases. To our knowledge, few published studies have actually measured the actual temperature of tea, coffee or maté drinking (reviewed in Ref. 22). Obtaining data on amount or frequency of drinking per day, total duration of drinking, sip size (or an indicator of this) and temperature of drinking are important. Unfortunately, many of the published studies did not collect data on several of these factors or did not report the results; studying the effect of hot-temperature drinks was not the main aim of most of these studies. Furthermore, few studies adjusted the results of drinking temperature for amount consumed and vice versa, and many studies failed to adjust the results for other confounders. Also, many studies combined the results for several types of beverages (e.g., tea and coffee), which made it difficult to look at effects of these drinks separately; this problem was more prominent for black and green tea use. A number of studies reported that the results were not significant but provided no counts or ORs (95% CIs). Such incomplete reporting prohibits use of the results in future meta-analyses. There is a large body of evidence suggesting that the risk factors for ESCC and EAC may be different. For example, there is strongevidence for a positive dose–response association between body mass index and risk of EAC,100 whereas several studies have reported an inverse association between body mass index and risk of ESCC.99 Nevertheless, few studies reported the results for ESCC and EAC separately.

Because of large heterogeneity in design and reporting and also incomplete reporting in several studies, we conducted a systematic review but avoided formal combination of the results as a meta-analysis. However, many of the limitations aforementioned can be addressed in future studies. Using a standard questionnaire across studies would help in collecting uniform data. Actual measurement of tea temperature is already being conducted in a cohort study in Iran,22, 101 where high rates of ESCC are seen.102, 103 In this study, 2 simultaneous cups of tea are poured; one is given to the study subject and a thermometer is put in the second cup.101 At intervals of 5°C (75°C, 70°C, 65°C, …) the subject is asked to sip the tea and tell the interviewer whether this is the usual temperature at which he/she drinks tea. This method for measuring tea temperature had shown a good repeatability101 and can be used in future studies, especially in areas with high risk of EC. Measurement of relevant metabolites in biological samples might be helpful to validate the self-reported data on amount of consumed beverages.

Thermal injury may cause EC via both direct and indirect pathways. Inflammatory processes associated with chronic irritation of the esophageal mucosa by local hyperthermia might stimulate the endogenous formation of reactive nitrogen species, and subsequently, nitrosamines.104 This hypothesis is supported by high rates of somatic G > A transitions in CpG dinucleotides of the TP53 gene in ESCC tumor samples from areas in which drinking hot beverages is considered an important risk factor for ESCC105–108; these mutations may indicate increased nitric oxide synthase activity in tumors.109 Thermal injury can also impair the barrier function of the esophageal epithelium, which may increase the risk of damage from exposure to intraluminal carcinogens.110 An association between hot drinks and precancerous lesion of the esophagus has also been reported.111, 112 Nevertheless, further prospective studies are indicated to investigate the association between high-temperature beverage or food consumption and risk of EC.

Chemical composition of tea, coffee and maté has been reviewed in detail elsewhere.21 Some constituents of tea, coffee and maté may have anticarcinogenic properties; for example, flavonoids and caffeine show antioxidant activities.12, 13, 113 Composition of the beverages may change during production procedures; for example, in production of black tea and coffee, fermentation of tea leaves reduces a large percentage of some flavonoids,12, 13 and severe roasting of coffee beans can considerably reduce their total cholorogenic acid content.21 Furthermore, black tea and maté may acquire some potentially carcinogenic contaminants, such as polycyclic aromatic hydrocarbons (PAHs) and mycotoxins, when being processed114, 115; high levels of PAH exposure has been reported among black tea and maté drinkers.116, 117 Both black and green tea drinking may increase plasma antioxidant activity in humans.118 On the other hand, in a clinical trial in Linxian and Huixian, China, decaffeinated green tea was not shown to have beneficial effects in alleviating esophageal precancerous lesions and abnormal cell proliferation patterns after 11 years of follow-up.119 Other hot foods and drinks, such as foods containing processed meat and preserved fish,120 may potentially have carcinogenic chemical constituents. However, most studies used in this review compared the intake of the same food in higher versus lower temperatures. Therefore, unless higher temperature results in further formation or release of carcinogens, the results should not be confounded by chemical constituents, and any association should be attributed to thermal injury.

Although the number of studies that reported inverse associations between amount of tea or coffee consumed is higher than the number of studies that showed positive associations, the overall results are mixed. Despite cancer preventive activity of tea in experimental studies, it is not clear why epidemiological studies have not consistently shown an inverse association between tea drinking and risk of EC. Furthermore, all of the epidemiological studies that showed a statistically significant inverse association between tea drinking and risk of EC were case–control studies. In case–control studies, a possible reduction in tea intake by EC cases following their symptoms might lead to underreporting of past tea consumption and, subsequently, result in spurious inverse associations. Tea and coffee contain several compounds other than flavonoids21 and may have some contaminants, whose interactions and complex metabolisms might alter the protective effect of the individual compounds.17 It has also been suggested that flavonoids, or other antioxidants, in high doses may act as pro-oxidant that can generate free radicals, which may lead to DNA damage and, finally, irreversible preneoplastic lesions (reviewed in Refs. 8 and 121).

In conclusion, there was little evidence for an association between EC risk and amount of tea or coffee consumed, but the results suggest an increased risk of EC associated with higher drinking temperature. Amount, duration and temperature of maté intake were all associated with higher EC risk, but the number of the studies that investigated these associations was limited. For other hot foods and drinks, there was some evidence showing increased risk with higher temperature. Overall, the available results strongly suggested that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data, and the results should be reported by histological subtypes of EC.

Ancillary