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Keywords:

  • green tea;
  • hot drinking;
  • esophageal cancer;
  • case–control study;
  • smoking;
  • alcohol drinking

Abstract

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Epidemiological studies suggested drinking green tea is inversely associated with esophageal cancer but results remain inconclusive. Moreover, inconsistent observations found high temperature drinks are associated with esophageal cancer. A population-based case–control study was conducted in a high-risk area (Dafeng) and a low-risk area (Ganyu) of esophageal cancer in Jiangsu province China from 2003 to 2007. It aimed to explore green tea drinking and tea temperature with the risk of esophageal cancer, and to compare the difference between different risk regions. Using identical protocols, 1,520 cases and 3,879 healthy controls were recruited as study subjects in 2 regions. Detailed information was collected to assess green tea drinking habits. Unconditional logistic regression was used to obtain OR and 95% CI. Results showed that ever drinking green tea elevated OR in both counties (Dafeng OR = 1.2, 95% CI = 0.9–1.5; Ganyu: OR = 1.9, 95% CI = 1.4–2.4). Drinking tea at high temperature was found to increase cancer risk in both areas (Dafeng: OR = 1.9, 95% CI = 1.2–2.9; Ganyu OR = 3.1 95% CI = 2.2–4.3). However, after further adjustment for tea temperature, ever drinking tea was not related to cancer in either county (Dafeng: OR = 1.0, 95% CI = 0.7–1.3; Ganyu: OR = 1.3, 95% CI = 0.9–1.7). For dose-response relationships, we observed positive relationship with monthly consumption of tea (p for trend = 0.067) and tea concentration (p for trend = 0.006) after further adjustment for tea temperature. In conclusion, green tea drinking was not inversely associated with esophageal cancer in this study. However, drinking tea at high temperatures significantly increased esophageal cancer risk. There was no obvious difference of green tea drinking between low- and high-risk areas. © 2008 Wiley-Liss, Inc.

Esophageal cancer is the sixth most common cause of cancer mortality worldwide. The number of new esophageal cancer cases in China accounted for 53% of all new cases in the world in 2002. The incidence and mortality rates (per 100,000) in China are 27.4 and 21.6 for men and 12.0 and 9.6 for women, respectively.1 Jiangsu Province, located in South-Eastern China, is one of the highest incidence areas of the disease. According to the Second National Death Cause Retrospective Survey, the mortality of esophageal cancer was 30 of 100,000 from 1990 to 1992 in Jiangsu province, much higher than the national average of 17 of 100,000.2 Although the mortality of esophageal cancer is high in most counties in Jiangsu; it differs considerably between counties, despite their similar geographic characteristics and socioeconomic status.3

Numerous epidemiological studies have demonstrated that environmental and lifestyle factors such as tobacco smoking, alcohol drinking and dietary habits are associated with the development of esophageal cancer.4, 5 It is also suggested that the consumption of green tea may help prevent esophageal cancer in humans.6, 7 Tea is currently grown in at least 30 countries, and it is the most frequently consumed beverage worldwide after water, especially in Asian countries such as China, Japan and India.8 The per capita worldwide consumption of tea is approximately 120 ml brewed tea per day.9 Depending on the manufacturing process, tea is classified into 3 major types: green tea (non-fermented), oolong tea (half-fermented) and black tea (fermented). Green tea is derived from Camellia sinesis, an evergreen shrub of the Theaceae family. It contains many polyphenols known as cathechins, including epigallo-cathechin-3 gallate (EGCG), epigallo-cathechin (EGC) and epicathechin-3 gallate (ECG).10 A number of studies have provided evidence that the polyphenolic antioxidants present in tea may be capable of affording protection against cancer.11–13

A few epidemiological studies have addressed the association between green tea and esophageal cancer, but results remain inconclusive.14–17 Moreover, inconsistent observations suggest that high-temperature drinks are associated with esophageal cancer.18 Since 2003, a population-based case–control study has been conducted in selected high- and low-risk areas of esophageal cancer in Jiangsu, China. In this analysis, we evaluate the association of esophageal cancer with green tea drinking and tea temperature in high- and low-risk areas. The results may help us improve the current understanding of the effects of green tea drinking and high-temperature drinking on the development of esophageal cancer.

Material and methods

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Study areas

A population-based case–control study has been conducted in 2 counties of Jiangsu province, Dafeng and Ganyu from 2003 to 2007. Both Dafeng and Ganyu are less developed, coastal, rural counties in northern Jiangsu province. The total population in Dafeng and Ganyu are approximately 0.7 million and 1.1 million, respectively. Dafeng has a higher mortality of esophageal cancer than Ganyu. From 1996 to 2002, the yearly average age-adjusted mortality of esophageal cancer was 36 of 100,000 in Dafeng, but was 24 of 100,000 in Ganyu during the same period.19

Study subjects

All subjects were restricted to local inhabitants who have lived in either area for at least 5 years. Newly diagnosed primary esophageal cancer patients from local adult residents were recruited as cases, using the data from local population based cancer registry agencies. The cancer registry agencies in both counties were established in the late 1990s and are part of the local Center for Disease Control and Prevention (CDC). All cases were identified by International Classification of Diseases, 10th revision (ICD-10, code C15). Second primary and recurrent cancers were excluded. A system of rapid case recognition was used in the study. All regional hospitals were required by the local health authorities to report new patients shortly after diagnosis. As the cancer registry agencies are attached to local CDC, investigators from local CDC could identify and interview the cases as quickly as possible. In this study, 68 and 75% of newly registered esophageal cancer cases were identified and interviewed in Dafeng and Ganyu, respectively. Because of the low proportion of pathological examination in less developed rural areas (Dafeng 61%, Ganyu 30%), patients who were diagnosed by other sophisticated methods such as endoscopic examination or radiology were also included.

Controls were derived from the same county as cases. Eligible controls were randomly selected from the general population, using the data of the county demographic database. Controls and cases were frequency matched by gender and age (±5 years). Individuals with history of cancer were not eligible as controls. The responding rate of control was 87% in Dafeng and 85% in Ganyu.

By study design, 600 cases and 600 controls in each county were required for the study. For Dafeng and Ganyu, recruitment of cases and controls was finished in 2006 and in 2007, respectively. As identical case–control studies on stomach, liver and lung cancer were also conducted in these 2 counties at the same time, controls for all cancer sites were used in this analysis. In total, 1,520 cases (637 in Dafeng County and 883 in Ganyu County) and 3,879 controls (1,938 in Dafeng County and 1,941 in Ganyu County) were recruited for this study.

Data collection

Using standard protocols and a pretested standardized epidemiologic questionnaire, with written informed consent, we collected epidemiological data by face-to-face interviews in both counties. Five milliliters of blood samples were collected at the time of interview.

The questionnaire included detailed information on known or potential risk or protective factors for esophageal cancer, including demographic information, socio-economic status, living conditions, environmental exposure, tobacco smoking, alcohol drinking, dietary habits, disease history, etc. Ever drinking green tea was defined as drinking at least 1 cup of green tea per week for more than 6 months. We collected lifetime general consumption of green tea drinking, and change of drinking pattern one year before diagnosis for cases or one year before interview for controls. Details of tea drinking habits included drinking status (current, former or never drinking), age when the person began to drink tea regularly, number of years drinking tea, monthly consumption of tea (grams/month), tea concentration and temperature of the water (boiling or not boiling) used to brew tea at the time of drinking. To validate the variables above, the questionnaire also collected information about the number of new cups of tea made each day (times the person changed the leaves in the tea cup), subsequent brewing of each cup (times the person poured new water into each cup without changing leaves).

In the rural areas of Jiangsu Province, China, seldom do people drink oolong tea or coffee, therefore, we did not include information on these 2 beverages in the questionnaire.

Statistical analysis

Data were entered into the computer by Epidata 2.1b, cleansed and analyzed using SAS v8.2 software. In the analysis, ever drinking green tea was further categorized into former drinking and current drinking; individuals who quit drinking because of health reasons but quit in less than 1 year at the time of interview were considered current drinkers. Smoking was categorized into ever smoking and never smoking. Pack-years of smoking were also calculated. Alcohol drinking was categorized into never or seldom drinking and often drinking. For body mass index (BMI), the Chinese recommended standard was used for the definition of overweight and obese: low weight (BMI < 18.5), overweight (BMI ≥ 24 and BMI < 28), obesity (BMI ≥ 28).20

Chi-square and Student t-tests were used to compare the distribution of potential risk or protective factors among control groups between the 2 counties. Unconditional logistic regression with a maximum likelihood estimation of parameters was applied for both univariate and multivariate analyses. The strength of the association was quantified as odds ratios (OR), and 95% confidence intervals (CI) around the OR were used to quantify precision. Dummy variables were used in the logistic regression to estimate OR for each exposure category. The trend test of ordered variables was performed by assigning scores to different exposure levels and treated the categorical variable as a continuous variable in the logistic regression model. Effect modification was analyzed by stratification. Statistical interaction was assessed by including main effect variables and their product terms in the logistic regression model.

On the basis of prior knowledge and confounding assessment, the effect of green tea was evaluated adjusting for age (continuous), gender (female = 0, male = 1), education level (ordered), income 10 years before (continuous), cancer family history of first degree relatives (No = 0, yes = 1), BMI (continuous), pack-years of smoking (continuous) and alcohol drinking (never or seldom = 0, often = 1). The effect after further adjustment for tea temperature was also presented (never drinker and normal tea temperature = 0, high tea temperature = 1).

Results

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

The demographic characteristics of cases and controls are shown by county in Table I, together with socio-economic related variables, cancer family history of first degree relatives, as well as smoking and alcohol drinking status.

Table I. Demographic Information and Epidemiologic Characteristics of Study Subjects in High and Low Risk Areas
 Dafeng (High)Ganyu (Low)p-Value1
Case (%) (N = 637)Control (%) (N = 1,938)OR (95% CI)Case (%)(N = 883)Control (%) (N = 1,941)OR (95% CI)
  • 1

    p-Value for comparing control groups between two counties.

  • 2

    Adjusted for age (continuous) and gender.

  • 3

    Chinese recommend standard was used for the definition of overweight and obesity: low weight (BMI < 18.5), overweight (BMI>= 24 and BMI < 28), obesity (BMI >= 28).

  • 4

    Adjusted for age (continuous), gender, education level, income 10 years before (continuous), cancer family history and BMI (continuous).

Gender    <0.01
 Males426 (66.9)1,368 (70.6) 765 (86.6)1,548 (79.8)  
 Females211 (33.1)570 (29.4) 118 (11.4)393 (20.2)  
Age    <0.01
 Mean ± SD (years)65.4 ± 9.063.6 ± 11.0 66.0 ± 9.965.1 ± 11.3  
 <5026 (4.1)227 (11.7) 42 (4.8)165 (8.5)  
 50–60131 (20.6)401 (20.7) 201 (22.8)426 (22.0)  
 60–70266 (41.8)681 (35.1) 281 (31.8)563 (29.0)  
 70–80177 (27.8)525 (27.1) 288 (32.6)632 (32.6)  
 ≥8037 (5.8)104 (5.4) 71 (8.0)155 (8.0)  
Education level      <0.01
 Illiteracy338 (53.1)827 (42.7)1.0 (referent)558 (63.3)1,230 (63.4)1.0 (referent) 
 Primary school214 (33.6)703 (36.3)0.8 (0.6–1.0)230 (26.1)467 (24.1)1.1 (0.9–1.3) 
 Middle school and above85 (13.3)407 (21.0)0.6 (0.4–0.8)94 (10.7)243 (12.5)0.9 (0.6–1.2) 
p for trend  <0.001  0.689 
Income 10 years ago      <0.01
 Mean ± SD1,792 ± 2,0262,293 ± 2,3661.0 (referent)21,493 ± 1,8121,773 ± 1,9531.0 (referent)2 
 <1,000148 (23.3)266 (13.8)0.7 (0.5–1.0)313 (36.2)632 (33.4)1.0 (0.8–1.3) 
 1,000–1,500123 (19.3)353 (18.3)0.6 (0.5–0.8)190 (22.0)394 (20.8)1.0 (0.8–1.2) 
 1,500–2,500194 (30.5)589 (30.6)0.5 (0.4–0.7)203 (23.5)444 (23.4)0.8 (0.6–1.0) 
 >2,500171 (27.0)718 (37.3)<0.001158 (18.3)424 (22.4)0.062 
p for trend (continuous)
Body Mass Index (BMI)3      0.27
 Mean ± SD20.8 ± 3.722.7 ± 6.01.0 (referent)222.2 ± 4.022.9 ± 3.61.0 (referent)2 
 Low (<18.5)162 (25.5)174 (9.0)2.8 (2.2–3.6)78 (8.9)104 (5.4)1.5 (1.1–2.1) 
 Normal (18.5–23.9)381 (60.0)1,175 (60.7)0.5 (0.4–0.6)636 (72.8)1,318 (68.2)0.6 (0.5–0.8) 
 Overweight (24–27.9)73 (11.5)471 (24.3)0.5 (0.3–0.9)125 (14.3)431 (22.3)1.0 (0.7–1.6) 
 Obesity (>=28)19 (3.0)115 (5.9)<0.00135 (4.0)80 (4.1)<0.001 
p for trend (continuous)
Cancer family history (First degree relatives)<0.01
No348 (54.4)1,178 (60.8)1.0 (referent)2730 (82.7)1,759 (90.6)1.0 (referent)2 
Yes289 (45.4)760 (39.2)1.4 (1.1–1.6)153 (17.3)182 (9.4)2.1 (1.6–2.6) 
Smoking status      <0.01
 Never smoke200 (31.4)817 (42.2)1.0 (referent)4215 (24.4)732 (37.7)1.0 (referent)4 
 Ever smoke437 (68.6)1,121 (57.8)1.4 (1.1–1.8)668 (75.6)1,209 (62.3)1.5 (1.2–1.9) 
Pack-years of smoking      <0.01
 Never smoker200 (31.4)817 (42.2)1.0 (referent)4215 (24.4)732 (37.7)1.0 (referent)4 
 <30 years187 (29.6)554 (28.6)1.2 (1.0–1.6)427 (48.4)852 (43.9)1.4 (1.1–1.8) 
 >=30 years250 (39.2)567 (29.3)1.6 (1.3–2.1)241 (33.4)357 (18.4)1.8 (1.4–2.4) 
p for trend (continuous)  0.029  0.011 
Alcohol drinking status      0.18
 Never or seldom354 (55.6)1,158 (59.8)1.0 (referent)4417 (47.2)1,200 (61.8)1.0 (referent)4 
 Often drinking283 (44.4)780 (40.2)1.3 (1.0–1.6)466 (52.8)741 (38.2)1.6 (1.3–1.9) 

Comparing the 2 counties, Ganyu has a higher proportion of male cases than Dafeng. Ganyu also has a lower educational level and lower previous income than Dafeng, as well as a lower prevalence of cancer family history (p < 0.01). Prevalence of smoking and green tea drinking in Dafeng is much lower than in Ganyu (p< 0.01). Although alcohol drinking appears to be higher in Dafeng, the difference was not statistically significant (p = 0.18). Within both counties, cases were older and more often male.

The OR and 95% CI for esophageal cancer with socio-economic status, cancer family history, smoking and alcohol drinking were also shown in Table I. Cases more frequently occurred in the population with lower socio-economic statuses, i.e., lower education level, lower previous income, and lower BMI. Cancer family history in first-degree relatives was found to significantly increase the risk of esophageal cancer (OR: Dafeng = 1.4, Ganyu = 2.1). An increased risk was observed among smokers in both counties (OR: Dafeng = 1.4, Ganyu = 1.5) as compared to nonsmokers. An apparent dose-response relationship was also found between esophageal cancer and pack-years of smoking (p for trend < 0.05). Similar to smoking, people who often drink alcohol tend to have a higher risk of esophageal cancer (OR: Dafeng = 1.3, Ganyu = 1.6) as compared to those who never or seldom drink alcohol.

Table II shows the association between esophageal cancer and green tea drinking in each county. After adjusting for potential confounders including age, gender, education level, previous income, cancer family history, BMI, pack-years of smoking and alcohol drinking, we found that ever drinking green tea significantly increased esophageal cancer risk in Ganyu (OR = 1.9, 95% CI = 1.4–2.4), but it was not significant in Dafeng (OR = 1.2, 95%CI = 0.9–1.5). Former drinking was observed to be strongly associated with increasing OR in both counties (Dafeng: OR = 3.4, 95% CI = 1.9–6.1; Ganyu: OR = 6.4, 95% CI = 3.6–11.5), whereas for current drinking, increased risk was found in Ganyu (OR = 1.6, 95% CI = 1.2–2.1) but not in Dafeng (OR = 1.0, 95% CI = 0.8–1.3). Tea temperature was found to be positively related to esophageal cancer risk in both counties, OR of drinking tea at high temperature was 1.9 in Dafeng (95% CI = 1.2–2.9) and 3.1 in Ganyu (95% CI = 2.2–4.3), as compared to never drinkers. When further adjusted tea temperature in the logistic regression model, we found ever drinking tea was not significantly related to esophageal cancer in either county (Dafeng: OR = 1.0, 95% CI = 0.7–1.3; Ganyu: OR = 1.3, 95% CI = 0.9–1.7). A positive association was still found in the former drinking group after adjusting tea temperature (Dafeng: OR = 2.2, 95% CI = 1.6–5.3; Ganyu: OR = 4.2, 95% CI = 2.3–7.6), but no significant association was observed among current green tea drinkers in either Dafeng or Ganyu.

Table II. The or and 95% CI of Esophageal Cancer Risk with Green Tea Drinking in High- and Low- Risk Areas
VariablesDafeng (High)Ganyu (Low)
Case/ControlOR1 (95% CI)1OR2 (95% CI)2Case/ControlOR1 (95% CI)1OR2 (95% CI)2
  • 1

    Adjusted for age (continuous), gender, education level, income 10 years before (continuous), cancer family history, BMI (continuous), pack-year of smoking (continuous), alcohol drinking.

  • 2

    Adjusted for above mentioned variables, further adjusted for tea temperature (never drinker and normal temperature = 0, high temperature = 1).

Green tea drinking
 Never drinking467/1,4011.0 (referent)1.0 (referent)384/1,1321.0 (referent)1.0 (referent)
 Ever drinking170/5371.2 (0.9–1.5)1.0 (0.7–1.3)499/8091.9 (1.4–2.4)1.3 (0.9–1.7)
 Former drinking33/423.4 (1.9–6.1)2.2 (1.6–5.3)95/446.4 (3.6–11.5)4.2 (2.3–7.6)
 Current drinking137/4951.0 (0.8–1.3)0.8 (0.6–1.1)404/7651.6 (1.2–2.1)1.1 (0.8–1.5)
Tea temperature    
 Never drinking467/1,4011.0 (referent) 384/1,1321.0 (referent) 
 Normal temperature118/4311.0 (0.7–1.3) 244/5531.3 (0.9–1.7) 
 High temperature51/1031.9 (1.2–2.9) 252/2483.1 (2.2–4.3) 
Age at tea drinking start
 Never drinking467/1,4011.0 (referent)1.0 (referent)384/1,1321.0 (referent)1.0 (referent)
 <2520/791.0 (0.6–1.8)0.8 (0.4–1.5)117/1771.8 (1.2–2.6)1.2 (0.8–1.9)
 25–3453/1511.4 (1.0–2.2)1.2 (0.8–1.8)255/3741.9 (1.4–2.6)1.3 (1.0–1.9)
 35–4437/1051.4 (0.9–2.2)1.2 (0.7–1.9)77/1641.6 (1.0–2.6)1.1 (0.7–1.8)
 ≥4558/2020.9 (0.6–1.4)0.8 (0.6–1.2)44/901.3 (0.6–2.6)0.9 (0.4–1.9)
p value for trend 0.5430.701 <0.0010.469
Years of tea drinking
 Never drinking467/1,4011.0 (referent)1.0 (referent)384/1,1321.0 (referent)1.0 (referent)
 <20 years65/2381.1 (0.8–1.5)1.0 (0.6–1.4)51/1461.2 (0.7–2.0)0.8 (0.5–1.5)
 20–34 years57/1761.1 (0.7–1.6)0.9 (0.6–1.4)227/3302.0 (1.5–2.8)1.4 (1.0–2.0)
 ≥35 years45/1231.4 (0.9–2.1)1.1 (0.7–1.8)209/3251.6 (1.2–2.3)1.1 (0.8–1.6)
p value for trend 0.1610.817 <0.0010.189
Monthly consumption of tea (g/month)
 Never drinking467/1,4011.0 (referent)1.0 (referent)384/1,1321.0 (referent)1.0 (referent)
 1–149 g109/3821.1 (0.8–1.4)1.0 (0.7–1.3)117/2441.5 (1.0–2.3)1.1 (0.7–1.7)
 150–249 g29/881.3 (0.8–2.1)1.0 (0.6–1.8)111/1851.4 (1.0–2.1)1.0 (0.7–1.6)
 ≥250 g27/621.4 (0.8–2.6)1.0 (0.6–2.0)264/3612.2 (1.7–3.0)1.6 (1.1–2.2)
p value for trend 0.1400.926 <0.0010.014
Tea concentration
 Never drinking467/1,4011.0 (referent)1.0 (referent)384/1,1321.0 (referent)1.0 (referent)
 Low29/1520.7 (0.4–1.1)0.6 (0.4–1.0)53/1371.3 (0.8–2.3)1.0 (0.6–1.7)
 Moderate75/2431.1 (0.8–1.6)1.0 (0.7–1.4)273/4521.7 (1.2–2.3)1.3 (0.9–1.8)
 High66/1421.7 (1.2–2.5)1.4(0.9–2.1)171/2132.4 (1.7–3.4)1.4 (0.9–2.1)
p value for trend 0.0160.235 <0.0010.059

Dose-response relationships for esophageal cancer risk with green tea-drinking related variables such as age at starting drinking, years of drinking, monthly consumption of tea (grams/month) and tea concentration were explored by county (Table II). We found earlier age at starting drinking, long years of drinking, higher grams of monthly tea consumption and high tea concentration were positively associated with cancer risk in both counties, though the trends were more apparent in Ganyu. However, after further adjustment for tea temperature, we only observed a positive dose-response relationship with monthly consumption of tea (p for trend = 0.014), and a borderline positive relationship with tea concentration (p for trend = 0.059) in Ganyu. No other apparent dose-response relationships were found.

Table III shows the effects of green tea drinking and dose-response relationships among the former drinking, current drinking group and their combination (ever drinking). As we did not find big difference between 2 counties (data not shown) and limited by the page width, pooled results of 2 counties are presented. In the former drinking group, green tea drinking significantly increased ORs despite the tea temperature. In the current drinking group, drinking in normal temperature did not increase the cancer risk (OR = 0.9, 95% CI = 0.8–1.2), but hot drinking elevated OR significantly (OR = 2.1, 95% CI = 1.6–2.8). Similar results were found in the ever drinking group, high tea temperature was found significantly increased OR (OR = 2.5, 95% CI = 1.9–3.2) but normal temperature did not (OR = 1.1, 95% CI = 0.9–1.3).

Table III. The or and 95% CI of Esophageal Cancer Risk with Green Tea Drinking in Different Groups in High- and Low-Risk Areas
VariablesFormer drinkingCurrent drinkingEver drinking3
OR1 (95% CI)1OR2 (95% CI)2OR1 (95% CI)1OR2 (95% CI)2OR1 (95% CI)1OR2 (95% CI)2
  • 1

    Adjusted for age (continuous variable), gender, education level, income 10 years before (continuous variable), cancer family history, BMI (continuous variable), pack-year of smoking (continuous variable), alcohol drinking and counties.

  • 2

    Adjusted for above mentioned variables, further adjusted for tea temperature (never drinker and normal temperature = 0, high temperature = 1).

  • 3

    Ever drinking is the combination o former drinking and current drinking.

Tea temperature   
 Never drinking1.0 (referent) 1.0 (referent) 1.0 (referent) 
 Normal temperature3.2 (2.0–5.1) 0.9 (0.8–1.2) 1.1 (0.9–1.3) 
 High temperature10.2 (4.8–21.6) 2.1 (1.6–2.8) 2.5 (1.9–3.2) 
Age at tea drinking start
 Never drinking1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)
 <255.4 (2.4–12.4)3.1 (1.2–7.9)1.2 (0.9–1.7)0.9 (0.6–1.3)1.4 (1.0–1.9)1.0 (0.8–1.5)
 25–346.4 (3.4–12.3)4.6 (2.3–9.3)1.5 (1.1–1.9)1.1 (0.8–1.4)1.7 (1.3–2.1)1.2 (1.0–1.6)
 35–444.4 (1.7–11.1)3.1 (1.2–8.2)1.3 (0.9–1.8)1.0 (0.7–1.4)1.4 (1.0–2.0)1.1 (0.8–1.5)
 ≥452.1 (0.9–5.0)1.6 (0.7–4.1)0.9 (0.6–1.2)0.7 (0.5–1.0)1.0 (0.7–1.3)0.8 (0.6–1.1)
p value for trend<0.0010.0030.2760.2410.1000.172
Years of tea drinking
 Never drinking1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)
 <20 years3.0 (1.5–5.8)2.3 (1.2–4.7)0.9 (0.66–1.2)0.7 (0.52–1.0)1.1 (0.79–1.42)0.9 (0.6–1.2)
 20–34 years5.0 (2.8–9.1)3.6 (1.9–6.5)1.3 (1.01–1.7)1.0 (0.74–1.3)1.5 (1.17–1.88)1.1 (0.9–1.4)
 ≥35 years6.8 (3.0–15.7)3.9 (1.5–10.0)1.3 (1.01–1.7)1.0 (0.73–1.3)1.5 (1.14–1.91)1.1 (0.8–1.4)
p value for trend<0.001<0.0010.0090.9650.4040.666
Monthly consumption of tea leaves (g/month)
 Never drinking1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)
 1–149 g3.9 (2.3–6.8)3.0 (1.6–5.4)1.0 (0.75–1.24)0.8 (0.6–1.0)1.2 (0.9–1.5)1.0 (0.7–1.2)
 150–249 g3.4 (1.3–8.4)2.6 (1.0–6.9)1.2 (0.88–1.69)0.9 (0.6–1.3)1.3 (1.0–1.8)1.0 (0.7–1.4)
 ≥250 g7.4 (3.5–15.5)4.4 (1.9–10.3)1.8 (1.36–2.31)1.3 (1.0–1.8)2.0 (1.5–2.5)1.4 (1.1–1.9)
p value for trend<0.0010.043<0.0010.2060.0230.067
Tea concentration
 Never drinking1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)1.0 (referent)
 Low2.1 (1.0–4.8)1.8 (0.8–4.2)0.8 (0.5–1.1)0.6 (0.4–0.9)0.9 (0.6–1.2)0.7 (0.5–1.0)
 Moderate3.9 (2.3–6.7)2.9 (1.6–5.4)1.2 (0.9–1.5)1.0 (0.8–1.2)1.3 (1.1–1.7)1.1 (0.9–1.4)
 High14.9 (5.8–38.1)9.7(3.5–26.7)1.6 (1.3–2.2)1.1(0.8–1.5)1.9 (1.5–2.4)1.3 (1.0–1.8)
p value for trend<0.001<0.001<0.0010.212<0.0010.006

Positive dose-response relationships were observed among former drinkers. Earlier age at starting drinking, long years of drinking, higher monthly consumption of tea and high tea concentration were found increasing ORs. Similar positive relations among the current drinking group were observed only before adjusting for tea temperature. For ever drinking, we found higher monthly consumption of tea (p for trend = 0.067) and usually drinking tea in high concentration (p for trend = 0.006) showed a positive tendency with cancer risk after adjusting for tea temperature.

Effect modification between green tea drinking and smoking status, pack-years of smoking, and alcohol drinking were evaluated by stratified analysis, pooled results of 2 counties are shown in Table IV. Former drinking individuals who had smoked, or had pack-years of smoking larger than 30, or had often drunk alcohol have the highest risk of esophageal cancer, but the interactions were not statistically significant.

Table IV. The Effect Modification of Esophageal Cancer Risk between Green Tea Drinking and Smoking, Pack-Years of Smoking, Alcohol Drinking
 Green tea drinking
NeverFormerCurrent
  • 1

    Adjusted for age (continuous), gender, education level, income 10 years before (continuous), cancer family history, BMI (continuous), alcohol drinking, tea temperature (never drinker and normal temperature = 0, high temperature = 1) and counties.

  • 2

    Adjusted for age (continuous), gender, education level, income 10 years before (continuous), cancer family history, BMI (continuous), pack-year of smoking (continuous), tea temperature (never drinker and normal temperature = 0, high temperature = 1) and counties.

Ever-smoking1
 No1.0 (referent)1.6 (0.8–3.2)0.7 (0.5–0.9)
 Yes1.3 (1.1–1.6)5.2 (3.6–7.5)1.3 (1.0–1.6)
p-Value forinteraction0.058  
Pack years of smoking1
 <301.0 (referent)3.1 (2.1–4.6)0.9 (0.7–1.0)
 >=301.4 (1.1–1.6)5.2 (3.1–8.7)1.4 (1.1–1.8)
p-Value for interaction0.224  
Alcohol drinking2
 No1.0 (referent)1.9 (0.9–3.9)0.8 (0.6–1.1)
 Yes1.2 (0.9–1.5)5.0 (3.0–8.4)1.1 (0.9–1.5)
p-Value for interaction0.450  

Table V shows the effect modification of hot drinking by smoking status, pack-years of smoking and alcohol drinking. Additive effects were found between drinking tea at high temperature and ever smoking, pack-years of smoking and ever drinking alcohol. The highest ORs were among hot drinking individuals who had smoked, or had pack-years of smoking larger than 30, or had often drunk alcohol, but these effect modifications were not statistically significant again.

Table V. The Effect Modification of Esophageal Cancer Risk between High Tea Temperature and Smoking, Pack-Years of Smoking, Alcohol Drinking
 High tea temperature1
NoYes
  • 1

    No, never drinker and normal tea temperature; Yes, drinking tea in high tea temperature.

  • 2

    Adjusted for age (continuous variable), gender, education level, income 10 years before (continuous variable), cancer family history, BMI (continuous variable), alcohol drinking and counties.

  • 3

    Adjusted for age (continuous variable), gender, education level, income 10 years before (continuous variable), cancer family history, BMI (continuous variable), pack-year of smoking (continuous variable) and counties.

Ever-smoking2
 No1.0 (referent)1.9 (1.2–2.9)
 Yes1.4 (1.2–1.7)3.2 (2.5–4.0)
 p-Value for interaction0.459 
Pack years of smoking2
 <301.0 (referent)2.1 (1.7–2.6)
 >=301.4 (1.2–1.7)3.6 (2.6–4.8)
 p-Value for interaction0.253 
Alcohol drinking3
 No1.0 (referent)2.2 (1.5–3.3)
 Yes1.2 (1.0–1.5)3.2 (2.3–4.2)
 p-Value for interaction0.616 

Discussion

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

This population-based case–control study, conducted in high- and low-risk areas of Jiangsu Province, China explored the association between green tea, hot tea drinking and esophageal cancer. Compared to previous studies, this study has the largest sample size and has addressed the association in different risk areas simultaneously. In the presented analysis; however, no obvious association between green tea drinking and esophageal cancer was observed in either high- or low- risk areas. On the contrary, drinking tea at high temperature was significantly related to the occurrence of esophageal cancer consistent in both high and low risk counties.

Green tea has been considered an herb medicine and a healthy beverage since ancient times. It is considered as a potential cancer preventive agent on the basis of numerous in vitro, in vivo and epidemiological studies.11–15 It has been suggested that the anti-oxidative and anti-inflammatory properties of green tea make it a promising agent for human cancer prevention.6 Tea polyphenols are known to be strong antioxidants. Cao et al. reported that green tea even has a much higher antioxidant activity against peroxyl radicals than some vegetables.21

Only a few studies have reported the relationship between green tea drinking and esophageal cancer with conflicting results. Some case–control studies carried out in Jiangsu and Shanghai, China, reported inverse association.14, 15, 22, 23 Gao et al. found that green tea drinking reduced the risk of esophageal cancer among women (OR = 0.50, 95% CI = 0.30–0.83) in Shanghai, and this risk decreased as tea consumption increased (p for trend < 0.01); the OR were also below 1.00 among men but were not statistically significant.14 Wang et al. reported that green tea drinking showed a protective effect in women (OR = 0.26; 95% CI = 0.07–0.94) in Jiangsu, but no dose-response relationship was found for tea-drinking duration.15 Another case–control study was also conducted in Jiangsu did not find an obvious protective effect.16 An intervention trial was conducted in Henan, another high risk province of China, where subjects with esophageal precancerous lesions were supplemented with decaffeinated green tea (DGT) 5 mg/day for 12 months. The results did not show an apparent difference between treatment and placebo groups.24 In consistent with our study, some studies conducted in western country also reported no association between tea drinking and esophageal cancer. Tavani reported OR = 0.9 (95% CI = 0.7–1.2) in a hospital-based case control study.25 La Vecchia found no association (RR = 1.0, 95% CI = 0.7–1.4) in another study in Italy.26

In this study, ever drinking green tea was positively associated with esophageal cancer risk in both low- and high-risk areas (Dafeng: OR = 1.2, 95% CI = 0.9–1.5; Ganyu OR = 1.9, 95% CI = 1.4–2.4). But after further adjusting for tea temperature, no significant association was observed either in Dafeng (OR = 1.0, 95% CI = 0.7–1.3) or in Ganyu (OR = 1.3, 95% CI = 0.9–1.7). Drinking beverages at high temperatures has been suggested as a cause of esophageal cancer by a number of studies.18 Hot drinking can cause thermal injury of esophageal mucosa and make it more susceptible to carcinogenesis. Our findings show that drinking tea at high temperatures had a 1.9- and 3.1-fold elevated risk in Dafeng and Ganyu. Additive effects between hot tea drinking and smoking, pack-years of smoking, as well as alcohol drinking were also observed in our study. Individuals who drank green tea at a high temperature, but who also smoked cigarettes or drank alcohol had the highest odds ratio for esophageal cancer, although the effect modifications were not statistically significant.

Kinjo et al. reported similar associations in a cohort study, the rate ratio was 1.6 (95% CI = 1.2–2.0) for hot tea (drinking green tea at high temperature) in comparison with non-hot tea (drinking green tea at moderate temperature).27 Another pooled analysis of 2 prospective cohorts in Japan found that as compared to never drinkers, drinking ≥ 5 cups of green tea/day significantly increased the risk of esophageal cancer (HR = 1.67, p for trend = 0.04). The population attributable fraction of esophageal cancer incidence attributed to green tea consumption was 22.1%, but as mentioned by the author, tea temperature could be a plausible explanation for the increased OR.17 Some cohort studies and case–control studies reported no association for hot drinks.28–30 In this population-based case–control study with relatively large sample size, we observed a strong association between drinking tea at a high-temperature and esophageal cancer.

We observed substantially elevated ORs in the former drinking group in 2 counties (Dafeng: OR = 2.2, Ganyu: OR = 4.2), even after adjusting for tea temperature. However, no significant association was found for current drinkers in either Dafeng (OR = 0.8) or Ganyu (OR = 1.1). This could be explained by cases who may be more likely to quit drinking tea because of early digestive tract symptoms. This higher proportion of former tea drinkers among cases may have caused an inflated OR in the former drinking group. However, in the current drinking group, the proportion of tea drinkers was lower than the fact because some cases quit drinking at an early time before disease onset, therefore the association might have been underestimated in this group. We even found that ORs were significantly changed if we used the combination of never drinkers and former drinkers as a reference group, then compared them with current drinkers (Dafeng: OR = 0.74, 95% CI = 0.54–0.99; Ganyu OR = 0.84, 95% CI = 0.63–1.22), but this change was attributed to potential bias. Therefore, how to avoid this kind of information bias should be carefully considered in future studies. In the presented analysis, as few numbers of former drinkers, the results of current drinking are more close to the real associations. The results of ever drinking (combination of former and current drinking) are similar to those in the current drinking group, and could be a better way to estimate the real associations.

After adjusting for potential confounders and tea temperature, earlier age at starting drinking, long drinking years, higher amount and higher concentration of tea drinking increased ORs apparently in the former drinking group; no clear tendency was observed in current drinkers, but again, there was a possibility of overestimation or underestimation of ORs in the former drinking and current drinking groups, respectively. When former and current drinking are combined together, positive dose-response trends were found with higher monthly consumption of tea (p for trend = 0.067) and high tea concentration (p for trend = 0.006) even after adjustment for tea temperature. A plausible explanation is drinking green tea is often accompanied by tobacco smoking and alcohol drinking among the Chinese population, people who frequently drink a high concentration of green tea are often heavy smokers or alcohol drinkers.31 Mu et al. reported a more than multiplicative interaction between green tea drinking and alcohol drinking (OR = 4.57; 95% CI = 1.62–12.89) in a study on stomach cancer.32 However, smoking and alcohol drinking were not observed as significant effect modifiers to tea drinking in the present study.

Several methodological issues need to be discussed. Potential selection bias and information bias may exist in any case–control study. A population-based study design and a random control selection method were used to minimize selection bias in our study. Cases were identified from the cancer registry data rather than from certain hospitals, controls were randomly selected from the county population demographic database, the response rate of cases and controls were 68 and 87% in Dafeng, 75 and 85% in Ganyu respectively. To reduce information bias, investigators were well trained to collect epidemiologic data in detail. Moreover, green tea related variables such as tea temperature, drinking years, monthly consumption of tea and tea concentration were also investigated and analyzed to avoid misclassification of exposure.

Confounding also has been considered in our analysis. Although the frequency matching method was applied in the study, controls for stomach, liver and lung cancers were also used in the present analysis. Therefore, differences of age and gender between case and control group were enlarged and might cause residual confounding, even after adjusting them in the logistic regression model. When sensitivity analysis was carried out with only esophageal cancer cases and their matched controls, the results were similar as for the overall analysis, the OR and 95% CI of former drinking and current drinking green tea was 2.2 (1.0–4.6) and 0.7 (0.5–1.0) in Dafeng, 3.6 (1.7–7.7) and 1.3 (0.9–1.8) in Ganyu, after adjusting for confounders and tea temperature.

There might be differences in the etiological factors between esophageal adenocarcinoma and squamous cell carcinoma. Because of the low pathological examination rate in less developed rural counties, it is difficult to differentiate between the subtypes of esophageal cancer in this population-based study. However, it has been reported that esophageal squamous-cell carcinoma represents more than 95% of esophageal cancer cases in China.33

In conclusion, green tea drinking was not inversely associated with esophageal cancer in this study in Jiangsu province, China. However, drinking tea at high temperatures is strongly associated with esophageal cancer. There was no obvious difference for the effects of green tea drinking between low- and high-risk areas.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

The authors thank the staffs of local Health Bureau and local CDC in Dafeng and Ganyu County, for their assistance in field works.

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  5. Discussion
  6. Acknowledgements
  7. References
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