Food groups and laryngeal cancer risk: A case-control study from Italy and Switzerland
Article first published online: 24 MAY 2002
Copyright © 2002 Wiley-Liss, Inc.
International Journal of Cancer
Volume 100, Issue 3, pages 355–360, 20 July 2002
How to Cite
Bosetti, C., La Vecchia, C., Talamini, R., Negri, E., Levi, F., Dal Maso, L. and Franceschi, S. (2002), Food groups and laryngeal cancer risk: A case-control study from Italy and Switzerland. Int. J. Cancer, 100: 355–360. doi: 10.1002/ijc.10485
- Issue published online: 27 JUN 2002
- Article first published online: 24 MAY 2002
- Manuscript Accepted: 15 APR 2002
- Manuscript Revised: 11 APR 2002
- Manuscript Received: 28 JAN 2002
- Italian Association for Cancer Research (AIRC)
- League Against Cancer of Italy and Vaud
- Swiss Foundation for Research Against Cancer
- laryngeal cancer;
- dietary fats;
- risk factors;
- case-control study
Besides tobacco and alcohol, diet has been thought to be associated with laryngeal cancer risk. We thus analyzed the role of various food groups, as well as specific seasoning fats, in a case-control study conducted in Northern Italy and the Swiss Canton of Vaud from 1992 to 2000. Our study included 527 incident, histologically confirmed cases and 1,297 frequency-matched controls, selected among patients admitted to the same hospitals as cases for acute, nonneoplastic conditions, unrelated to smoking, alcohol consumption and long-term modifications of diet. The subjects' usual diet was investigated through a validated food frequency questionnaire, including 78 foods and beverages. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. After adjustment for major confounding factors, a significant trend of increasing risk was observed for eggs (OR = 1.7 for the highest compared to the lowest quintile), red meat (OR = 3.1), processed meat (OR = 1.7), fish (OR = 1.6) and sugars (OR = 1.6). Significant inverse associations were observed for pulses (OR = 0.7), raw vegetables (OR = 0.2), cooked vegetables (OR = 0.3), citrus fruit (OR = 0.6) and other fruit (OR = 0.5). In regard to seasoning fats, a significant reduction of cancer risk was observed for olive oil (OR = 0.4) and specific seed oils (OR = 0.6), while mixed seed oils were directly associated with laryngeal cancer risk (OR = 2.2). Our study suggests that increasing vegetables and fruit, decreasing meat consumption and perhaps substituting olive oil or specific seed oils for other types of seasoning lipids might help reduce laryngeal cancer risk. © 2002 Wiley-Liss, Inc.
Tobacco and alcohol are the 2 major risk factors for cancer of the larynx.1, 2 Their importance is reflected by a higher incidence of laryngeal cancer in males compared to females3 and by higher incidence and mortality rates in countries, such as Italy, France and Spain, where heavy alcohol drinking is widespread.4
Among other factors, diet has been associated with laryngeal cancer risk.5, 6 A consistent protective effect of fruit and vegetables has been reported in several case-control studies.7, 8, 9, 10, 11, 12, 13, 14 An Italian study, including 110 male cases and 843 controls, reported a reduced risk of laryngeal cancer for subjects with high consumption of green vegetables (odds ratio [OR] = 0.4) and fresh fruit (OR = 0.6).9 In a Polish study on 249 laryngeal cancer cases and 965 controls, the relative risk (RR) was 2.9 for low vegetable and fruit consumption combined.10 A population-based case-control study from Shanghai, China, on 201 incident cases and 414 controls found a protective effect for high intake of citrus fruit (OR = 0.4) and some dark green vegetables (OR = 0.3).12 A multicentric case-control investigation carried out in 6 regions from Spain, Italy, Switzerland and France, including 1,147 male cases and 3,057 population controls, reported increased risk of cancer of the endolarynx for low intake of fruit (OR = 1.4), citrus fruit (OR = 1.6) and vegetables (OR = 1.7) and even stronger risks for cancer of the hypopharynx and epilarynx.13 In a case-control study conducted in Uruguay on 148 cancer cases and 444 hospital controls, an OR of 0.4 was found for high consumption of plant foods and a stronger reduction in risk for all fruits (OR = 0.4) and raw vegetables (OR = 0.3).14
The evidence of an association between other foods and laryngeal cancer risk is limited and inconsistent.5, 6 There are, however, suggestions of a possible protective effect of fish8, 9, 13 and of a detrimental one of eggs,8, 11 whereas meat has been inconsistently related to laryngeal cancer risk.8, 9, 11–13, 15 In relation to fats, there are indications that vegetable oils are inversely related to laryngeal cancer risk,8, 13 whereas butter is directly associated.13
MATERIAL AND METHODS
A case-control study of cancer of the larynx was conducted from 1992 to 2000 in 2 Italian areas (the provinces of Pordenone in northeastern Italy and the greater Milan area in northern Italy) and in the Swiss Canton of Vaud. Cases were 527 patients (478 men and 49 women, median age 61 years, range 30–79) admitted to major teaching and general hospitals in the areas under study with incident, histologically confirmed squamous cell carcinoma of the larynx, diagnosed no longer than 1 year before the interview. Laryngeal cancer cases included 271 glottis [International Classification of Diseases (ICD-IX): 161.0], 117 supraglottis (ICD-IX: 161.1), 4 subglottis (ICD-IX: 161.2), 5 laryngeal cartilage (ICD-IX: 161.3), 19 overlapping lesions of larynx (ICD-IX: 161.8) and 111 unspecified sites (ICD-IX: 161.9). Controls were 1,297 subjects (1,052 men and 245 women, median age 61 years, range 31–79) frequency-matched with cases by 5-year age groups, sex and area of residence, selected among patients admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions, not related to smoking, alcohol consumption and long-term modification of diet. To compensate for the rarity of laryngeal cancer in women, a control-to-case ratio of about 5 was chosen for females, as opposed to 2 for males. Twenty seven percent of the controls were admitted for traumas, 22% for other orthopedic disorders, 29% for acute surgical conditions and 23% for miscellaneous other illnesses, including eye, nose, ear, skin or dental disorders.
Cases and controls were interviewed during their hospital stay using a structured questionnaire, administered by ad hoc trained interviewers. Information was collected on sociodemographic characteristics, anthropometric measures, lifestyle habits, including tobacco smoking and alcohol drinking, personal medical history and family history of cancer in first-degree relatives.
The subjects' usual diet during the 2 years prior to cancer diagnosis or hospital admission (for controls) was investigated through an interview-administered FFQ, including 78 foods and beverages, as well as a range of recipes, i.e., the most common ones in the Italian and Swiss diet, grouped into 7 sections: (i) bread and cereal dishes (first courses); (ii) meat and other main dishes (second courses); (iii) vegetables (side dishes); (iv) fruit; (v) sweets, desserts and soft drinks; (vi) milk, hot beverages and sweeteners; (vii) alcoholic beverages. The FFQ showed satisfactory validity16 and reproducibility,17 with Spearman correlation coefficients between 0.60 and 0.80 for most food items. Subjects were asked to indicate the average weekly frequency of consumption of each dietary item; intakes lower than once a week, but at least once a month, were coded as 0.5 per week. A commonly used unit or serving size was specified for 40 items, whereas for the remainders portion was defined as small, average or large, with the help of figures. For a few vegetables and fruits, seasonal consumption and the corresponding duration was elicited. To estimate total energy intake, an Italian food composition database, integrated with other sources when needed, was used.18 Several questions aimed to assess the fat intake pattern were also included in the questionnaire and used to derive quantitative estimates of intake of various seasoning fats, such as olive oil, specific seed oils (i.e., sunflower, maize, peanut and soya), mixed seed oils, margarine and butter.
Food items and recipes were categorized into 19 food groups: milk and dairy products, coffee and tea, bread, pasta and rice, soups, eggs, poultry, red meat, processed meat, fish, cheese, pulses (i.e., green peas, beans, lentils, etc.), raw vegetables, cooked vegetables, potatoes, citrus fruit, other fruit, desserts and sugar. The weekly intake for each food group was obtained by summing up the frequency of consumption for each individual food item in the same group and was then distributed into approximate quintiles among controls.
Odds ratios (OR) and the corresponding 95% confidence intervals (CI) for quintile of intake of each food item were estimated using unconditional multiple logistic regression models.19 All models included terms for age (5-year groups), sex, area of residence, years of education (<7, 7–11, ≥12), tobacco smoking (never, ex-smoker, current smoker of <15, 15–24, ≥25 cigarettes/day), alcohol drinking (<14, 14–27, 28–55, ≥56 drinks/week, plus a dummy variable for ex-drinkers) and nonalcohol energy intake (quintiles). Tests for trend were based on the likelihood ratio test between models with and without a linear term for each food group. The OR for an increase of 1 average serving per day was also estimated, including each food item in the model as a continuous variable, with an increment of 7 servings per week. The modifying effect of various covariates was tested by computing the difference in the −2 log likelihood between models with and without interaction terms and referring it to the χ2 distribution with degrees of freedom equal to the number of interaction terms minus one.
Table I gives the distribution of 527 laryngeal cancer cases and 1,279 controls according to age, sex, tobacco and alcohol consumption. By design, the proportion of women was higher in controls than in cases, and the age distribution was similar in cases and controls. Tobacco smoking and alcohol drinking were significantly higher in cases (OR = 19.8 for current smokers, and 1.8 for current drinkers).
|< 15 cigarettes/day||58||11.1||146||11.3|
|≥ 25 cigarettes/day||102||19.4||63||4.9|
|Alcohol intake1 (drinks/week)|
Table II shows the distribution of 19 food groups according to quintile of intake, and the corresponding multivariate ORs. Intake of milk, coffee and tea, bread, pasta and rice,soups, poultry, cheese, potatoes and desserts were not significantly associated with laryngeal cancer. A significant trend of increasing risk with increasing quintile of intake was observed for eggs (OR = 1.7, 95% CI: 1.1–2.8 for the highest compared to the lowest quintile), red meat (OR = 3.1, 95% CI: 1.9–5.0), processed meat (OR = 1.7, 95% CI: 1.0–2.7), fish (OR = 1.6, 95% CI: 1.2–2.2) and sugars (OR = 1.6, 95% CI: 1.0–2.3). Significant inverse associations were observed for pulses (OR = 0.7, 95% CI: 0.5–0.9), raw vegetables (OR = 0.2, 95% CI: 0.1–0.3), cooked vegetables (OR = 0.3, 95% CI: 0.2–0.5), citrus fruit (OR = 0.6, 95% CI: 0.4–0.9) and other fruit (OR = 0.5, 95% CI: 0.4–0.8). When foods significantly (p < 0.001) related to laryngeal cancer risk were entered simultaneously in a logistic regression model, all the associations shown in Table II persisted, thus showing them to be independent from each other.
|Food group (servings per week)||Quintile of intake||χ2 trend (p-value)|
|Coffee and tea|
|Pasta and rice|
With reference to individual food items, an increased risk of laryngeal cancer was observed for all deep-fried foods included in our questionnaire. The OR for the highest tertile of consumption, as compared to the lowest one, was 1.9 for fried eggs, 1.4 for fried chicken, 1.6 for fried beef or pork, 3.1 for fried fish. The inverse association with vegetables was similar for most vegetables examined; strongest reductions in risk were observed for raw carrots (OR = 0.4 for the highest tertile of consumption vs. the lowest one) and tomatoes (OR = 0.3). Among fruits, the strongest protective effect was observed for kiwi (OR = 0.6), oranges and other citrus fruits (OR = 0.6), grapes (OR = 0.4) and strawberries and other berries (OR = 0.5).
Table III presents the ORs for an intake increase of 1 serving per day of the food groups significantly associated (p < 0.001) with laryngeal cancer risk in strata of age (<60 years, ≥60 years), alcohol drinking (<28 drinks/week, ≥28 drinks/week) and tobacco smoking (never smokers plus ex-smokers for 20 or more years, smokers plus ex-smokers for less than 20 years). The risk estimates were consistent in strata of the considered covariates, thus indicating the absence of any substantial interaction on a multiplicative scale between the intake of these food groups and the 2 major risk factors of laryngeal cancer.
|Food group||OR1 (95% CI)|
|Age (years)||Alcohol (drinks/week)||Tobacco smoking|
|< 60||≥60||< 28||≥ 28||Non-smoker2||Smoker3|
|Red meat||2.64 (1.51–4.62)||2.26 (1.35–3.80)||2.78 (1.43–5.41)||2.33 (1.46–3.72)||1.12 (0.46–2.71)||2.89 (1.87–4.45)|
|Raw vegetables||0.51 (0.38–0.68)||0.49 (0.37–0.64)||0.33 (0.22–0.49)||0.60 (0.48–0.76)||0.55 (0.34–0.89)||0.48 (0.38–0.60)|
|Cooked vegetables||0.36 (0.19–0.68)||0.22 (0.12–0.40)||0.34 (0.16–0.74)||0.27 (0.16–0.45)||0.71 (0.26–1.92)||0.24 (0.15–0.38)|
|All vegetables||0.52 (0.41–0.67)||0.46 (0.36–0.58)||0.37 (0.27–0.52)||0.56 (0.46–0.69)||0.59 (0.39–0.91)||0.47 (0.39–0.57)|
|All fruit||0.84 (0.74–0.97)||0.91 (0.81–1.03)||0.87 (0.75–1.01)||0.90 (0.81–1.00)||0.88 (0.71–1.10)||0.89 (0.81–0.98)|
Similar ORs were observed also when foods significantly associated with laryngeal cancer risk were examined in different subsites of laryngeal cancer (i.e., cancers of the supraglottis, including epiglottis, false cords and laryngeal ventricles, and of the glottis, including true vocal cord) (Table IV).
|Food group||OR (95% CI)|
|Red meat||2.03 (1.29–3.20)||2.48 (1.22–5.03)||3.08 (1.73–5.49)|
|Raw vegetables||0.56 (0.44–0.70)||0.52 (0.36–0.75)||0.41 (0.29–0.58)|
|Cooked vegetables||0.20 (0.11–0.40)||0.49 (0.25–0.99)||0.25 (0.12–0.52)|
|All vegetables||0.51 (0.42–0.63)||0.56 (0.41–0.76)||0.42 (0.31–0.56)|
|All fruit||0.95 (0.85–1.05)||0.94 (0.79–1.10)||0.73 (0.62–0.87)|
The association of seasoning fats and laryngeal cancer risk is considered in Table V. A significant reduction of cancer risk was observed for olive oil (OR = 0.4, 95% CI: 0.3–0.7, for the highest compared to the lowest quintile) and specific seed oils (OR = 0.6, 95% CI: 0.4–0.9), while mixed seed oils were directly associated with laryngeal cancer risk (OR = 2.2, 95% CI: 1.3–3.5). No significant associations emerged for consumption of butter and margarine. The inverse relation between olive oil, as well as specific seed oils, and laryngeal cancer risk was attenuated after adjustment for total vegetables, which are likely to be consumed with oil; no apparent modifications occurred to risk estimates for other oils or fats.
|Fats (grams per week)||Quintile of intake||χ2 trend (P-value)|
|Specific seed oils4,5|
|Mixed seed oils|
Our study, based on a uniquely large dataset, confirms the existence of a beneficial effect of a diet rich in vegetables and fruit on laryngeal carcinogenesis. This finding is consistent with the results from other case-control studies on diet and laryngeal cancer7, 8, 9, 10, 11, 12, 13, 14 and from a few prospective investigations on cancers of the upper aerodigestive tract.20, 21
A protection was found both for raw and cooked vegetable consumption, as well as for pulse intake; it also appeared to be consistently conferred by all vegetables examined, with a somewhat stronger effect of carrots and tomatoes.12, 14 In agreement with another investigation,14 no association was found with intake of potatoes, possibly on account of their higher calorie yield and low vitamin content. Similarly, both citrus fruit and other fruit items were inversely related to laryngeal cancer risk.
The beneficial effect of vegetables and fruit can be related to their content of several micronutrients, such as carotenoids, vitamins C and E, flavonoids and phytosterols, known to have strong antioxidant and anticarcinogenic properties.22 Carotene and vitamin C, in particular, have been inversely related to laryngeal cancer risk,12, 13, 23–25 although the evidence for the potential favorable effect of any specific micronutrient is less consistent than that for vegetables and fruit. Thus, it is still unclear whether the effects of vegetables and fruit are due to these micronutrients, or if the combined effect of several concurrent mechanisms can explain their favorable effect on laryngeal cancer.
In our study, red and processed meat, eggs and fish were associated with an increased risk of laryngeal cancer risk. No association was, however, found with poultry and cheese. Although meat has not been consistently related to laryngeal cancer risk, a possible detrimental effect of meat has been suggested by two other studies: a study from China12 found an increased risk for liver and salted meat, and another from Uruguay found an OR similar to ours for red meat and increased risks for other specific types of meat, too, although after adjustment for total fat intake, only lamb meat remained associated.15 The meat effect could be due to its content of fat, found to be positively related to laryngeal cancer risk in another study.25 Other substances or nutrients may be responsible for the increased risk, including heterocyclic amines, resulting from cooking. These substances have been associated with the risk of upper digestive tract cancers26 as well as of other neoplasms.27 No information on doneness of meat or biomarkers of specific heterocyclic amines were, however, available in our dataset.
A direct relation with elevated egg consumption was observed and has been also reported in 2 other studies.8, 11 This association could again reflect an unfavorable effect of animal fats, but—as for other foods—it may be a general indicator of a poorer diet. Consumption of eggs in this population is, in any case, relatively infrequent.
The direct association with fish intake is, on the other hand, somewhat surprising. Fish has been reported to have a beneficial effect on laryngeal8, 9, 13 and other cancer sites, probably on account of its content of polyunsaturated fats, and potential beneficial nutrients, including omega-3 fatty acids.28 However, analyzing each single fish item included in this food group, we observed that an increased risk was found only for fried fish. Thus, it is unlikely that fish is per se associated with laryngeal cancer risk.
The associations with vegetables and fruit and meat were consistent across strata of age, sex, tobacco smoking and alcohol drinking, thus showing them to be independent from the 2 major risk factors for laryngeal cancer. Moreover, the multivariate ORs were similar in various subsites of laryngeal cancer.
An additional interesting finding of our study is the association with selected seasoning fats: olive oil and specific seed oils were protective for laryngeal cancer, although their effect was mitigated after adjustment for total vegetables, likely to be consumed with these oils. Mixed seed oils appeared to be associated with an increased risk, whereas no meaningful relation was found for butter and margarine.
A beneficial effect of olive oil has been reported for several other neoplasms,29 including cancer of the oral cavity and pharynx30 and esophagus.31 This could be explained by its antioxidant properties, due both to oleic acid itself and to the presence of other antioxidants, such as vitamin E and polyphenols.32 It is also possible that the observed associations with olive oil and specific seed oils are not due to specific components of these seasoning lipids, but to the fact that they are indicators of healthier dietary habits and possibly other beneficial lifestyle factors. Along the same line, mixed seed oils, which are frequently used for frying, may represent an unfavorable diet.
Among the limitations of our study, there are the possible biases of hospital-based case-control studies. However, in order to reduce any information bias, the questionnaire was administered to both cases and controls by the same interviewers under similar conditions. We also selected controls with admission diagnosis diseases unrelated to tobacco smoking, alcohol drinking and diet. In regard to the information on diet, although inaccuracies of FFQ have been reported,33 the dietary questionnaire used in our study has shown satisfactory reproducibility and validity.16, 17 Bias in the recall of food intake should be limited in this population that is not particularly health conscious and by using hospital instead of health controls. To minimize any possible recall bias due to the onset or treatment of the disease, we asked dietary habits in the 2 years prior to interview.
Among the strengths of our study are the high participation rate of cases and controls, the comparable catchment areas of study subjects, the strict control for tobacco and alcohol, as well as other potential confounding factors resulting from matching by sex, age and area of residence. Moreover, the use of a FFQ allowed us to take into account the full dietary pattern and to adjust for total energy intake.34
In conclusion, our investigation suggests that increasing vegetables and fruit, decreasing meat consumption and perhaps substituting olive oil or specific seed oils for other types of seasoning lipids might help reducing laryngeal cancer risk.
C.B. was supported by an AIRC/FIRC fellowship. The authors thank Ms. C. Pasche and Ms. F. Lucchini for data collection and validation, and Ms. M.P. Bonifacino for editorial assistance.
- 1International Agency for Research on Cancer. Tobacco smoking. IARC Monogr Eval Carcinog Risks Hum, vol. 38. Lyon: IARC, 1986.
- 2International Agency for Research on Cancer. Alcohol drinking. IARC Monogr Eval Carcinog Risks Hum, vol. 44. Lyon: IARC, 1988.
- 4Cancer incidence and mortality in Europe, 1988–1992. J Epidemiol Biostat 1998;3: 295–373., , , , .
- 5World Cancer Research Fund in association with the American Institute for Cancer Research. Food, nutrition and the prevention of cancer: a global perspective. Washington, DC: World Cancer Research Fund, 1997.
- 19Statistical methods in cancer research. vol. I. The analysis of case-control studies. IARC Sci Publ 32. Lyon: IARC, 1980., .
- 22Vegetables, fruit and phytoestrogens as preventive agents. In: StewartBW, McGregorD, KleihuesP, eds. Principles of chemoprevention. IARC Sci Publ 139. Lyon: IARC, 1996., .
- 27International Agency for Research on Cancer. Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. IARC Monogr Eval Carcinog Risks Hum, vol. 56. Lyon: IARC, 1993.