Diet diversity and the risk of laryngeal cancer: A case–control study from Italy and Switzerland

Introduction 

Several studies have investigated the relation between laryngeal cancer risk and specific dietary components (foods and nutrients).1, 2 However, only scant attention has been paid to the definition of potential correlates of laryngeal cancer risk in terms of general dietary patterns.

Food diversity (i.e., the variety of foods consumed) has been recommended to achieve a healthy diet in cancer prevention.3, 4, 5 The relation between diet diversity and all-cause mortality was analyzed in the First National Health Epidemiologic Follow-up Study,3 which found an inverse relation after adjustment for several confounders. The role of diet diversity has been investigated on the risk of a few cancer sites, including colon,6, 7 colorectal,8, 9 breast,10 gastric11 and oral and pharyngeal cancer.12 No study investigated the relation between diet diversity and laryngeal cancer.

Thus, to provide further information on the potential role of total diet and specific food group diversity on the risk of laryngeal cancer, we considered data from a large multicenter case–control study conducted in Italy and Switzerland.

Materials and methods 

A case–control study of laryngeal cancer was conducted in Italy and Switzerland between 1992 and 2000.13 Briefly, cases were 527 patients (478 men and 49 women; median age 61 years, range 30–79 years) admitted to major teaching and general hospitals in the study areas, with incident, histologically confirmed cancer of the larynx, diagnosed no longer than one year before the interview. Controls were 1297 subjects (1052 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, non-neoplastic 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 women, as opposed to 2 for men. Twenty seven percent of the controls were admitted for traumas, 22% for other orthopedic disorders, 28% for acute surgical conditions and 23% for miscellaneous other illnesses, including eye, nose, ear, skin or dental disorders. Less than 5% of both cases and controls approached for interview refused to participate.

Cases and controls were interviewed during their hospital stay by trained interviewers using a structured questionnaire. This included information on socio-demographic characteristics, lifestyle habits, such as tobacco smoking and alcohol drinking, anthropometric measures, personal medical history, and family history of cancer. The subjects’ usual diet during the 2 years prior to cancer diagnosis or hospital admission (for controls) was investigated through an interview-administered food frequency questionnaire (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 and (vii) alcoholic beverages. The FFQ showed satisfactory validity14 and reproducibility.15 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. To estimate total energy intake, an Italian food composition database, integrated with other sources when needed, was used.16

Total diversity was computed as the total number of different foods consumed at least once per week.11 We also computed diversity within four food groups: vegetables, fruit, meat, and cereals. Subjects were categorized into approximate quartiles of total diet diversity or specific food group diversity based on the distribution of controls.

Odds ratios (OR) of laryngeal cancer and the corresponding 95% confidence intervals (CI) according to various measures of food diversity were derived from multiple unconditional logistic regression equations.17 Allowance was made for age, sex, study centre, years of education, tobacco smoking, alcohol drinking, and non-alcohol energy intake. In the stratified analyses, diversity was included in the models as a continuous variable, and the OR for an increment equal to one standard deviation (SD) of the control distribution was computed.

Results 

Table 1 gives the ORs of laryngeal cancer according to quartile of intake of total, vegetable, fruit, meat, and cereal food diversity. A significant inverse association was observed for vegetable (OR=0.41, 95% CI: 0.28–0.59, for the highest versus the lowest quartile), and fruit diversity (OR=0.40, 95% CI: 0.27–0.59). Conversely, a direct association was found for meat diversity (OR=1.67, 95% CI: 1.11–2.50). No significant association was found for total and cereal food diversity.

Table 1. Odds ratios (OR) and corresponding 95% confidence intervals (CI) of 527 laryngeal cancer cases and 1297 controls according to diversity of intake of selected food groups. Italy and Switzerland, 1992–2000

	Diet diversitya	Cases	Controls	ORb (95% CI)
		No. (%)	No. (%)
	Total diversity
	<25	123 (23.3)	297 (22.9)	1c
	25 to <30	161 (30.6)	338 (26.0)	1.16 (0.82–1.64)
	30 to <35	142 (26.9)	337 (26.0)	0.94 (0.65–1.36)
	⩾35	101 (19.2)	325 (25.1)	0.76 (0.50–1.15)
	χ2trend (p value)			2.33 (0.13)
	Vegetable diversity
	<4	120 (22.8)	193 (14.9)	1c
	4 to <6	195 (37.0)	374 (28.8)	0.86 (0.60–1.22)
	6 to <7	90 (17.1)	238 (18.4)	0.62 (0.41–0.93)
	⩾7	122 (23.1)	492 (37.9)	0.41 (0.28–0.59)
	χ2trend (p-value)			29.25 (<0.0001)
	Fruit diversity
	<3	152 (28.8)	197 (15.2)	1c
	3 to <4	88 (16.7)	199 (15.3)	0.66 (0.45–0.98)
	4 to <6	191 (36.3)	510 (39.3)	0.55 (0.39–0.76)
	⩾6	96 (18.2)	391 (30.2)	0.40 (0.27–0.59)
	χ2trend (p value)			23.34 (<0.0001)
	Meat diversity
	<3	65 (12.3)	232 (17.7)	1c
	3 to <5	147 (27.9)	402 (31.0)	1.26 (0.85–1.85)
	5 to <6	91 (17.3)	204 (15.7)	1.52 (0.98–2.35)
	⩾6	230 (43.7)	204 (15.7)	1.67 (1.11–2.50)
	χ2trend (p value)			6.71 (0.01)
	Cereal diversity
	<4	63 (12.0)	196 (15.1)	1c
	4 to <6	164 (31.1)	452 (34.9)	1.01 (0.66–1.52)
	6 to <7	125 (23.7)	249 (19.2)	1.27 (0.81–2.00)
	⩾7	175 (33.2)	400 (30.8)	1.12 (0.72–1.74)
	χ2trend (p value)			0.06 (0.68)

a Number of items consumed at least weekly. b Estimates from multiple logistic regression adjusted for age, sex, study centre, education, tobacco smoking, alcohol drinking, and non-alcohol energy intake. c Reference category.

Table 2 shows the ORs according to diversity of intake of selected food groups in separate strata of age (<60 and ⩾60 years), alcohol drinking (<28 and ⩾28 drinks per week) and tobacco smoking (never smokers and smokers). No significant heterogeneity in risk estimates emerged across strata of various covariates considered.

Table 2. Odds ratios (OR) and corresponding 95% confidence intervals (CI) of 527 laryngeal cancer cases and 1297 controls according to diversity of intake of selected food groups in strata of age, alcohol and tobacco smoking. Italy and Switzerland, 1992–2000

	Diet diversitya	ORb (95% CI)
		Age (years)		Alcohol drinking (drinks/week)		Tobacco smoking
		<60	⩾60	<28	⩾28	Never-smokersc	Ever-smokersd
	Vegetable diversity	0.66 (0.54–0.80)	0.70 (0.59–0.83)	0.62 (0.50–0.77)	0.72 (0.61–0.84)	0.81 (0.67–0.97)	0.59 (0.50–0.71)
	Fruit diversity	0.66 (0.55–0.80)	0.81 (0.68–0.96)	0.71 (0.58–0.89)	0.76 (0.65–0.89)	0.79 (0.65–0.95)	0.70 (0.60–0.83)
	Meat diversity	1.34 (1.11–1.61)	1.30 (1.10–1.53)	1.20 (0.98–1.47)	1.38 (1.18–1.61)	1.22 (1.03–1.46)	1.39 (1.17–1.65)

a Number of items consumed at least weekly. b Estimates from unconditional logistic regression adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking, and non alcoholic energy intake. OR for an increment equal to one standard deviation of the control distribution. c Including never-smokers and ex-smokers for 20 or more years. d Including smokers and ex-smokers for less than 20 years.

Discussion 

Our study, based on a uniquely large dataset, indicates the existence of a beneficial effect of a diet rich in various different vegetables and fruit on laryngeal carcinogenesis. These findings are consistent with the results from other case–control studies on diet diversity and selected other cancers. A protective effect was found between vegetable diversity and colorectal cancer,8, 9 and between vegetable and fruit diversity and stomach11 and oral and phorymgeol cancer.12 The variety of vegetables consumed seems also to have a beneficial role on breast cancer.10 Moreover, meat diversity was directly associated with oral and pharyngeal cancer,12 and with colon cancer only for men.7

The beneficial effect of a diet rich in various vegetables and fruit can be related to the high content of several micronutrients and compounds, such as carotenoids, vitamins C and E, flavonoids and phytosterols, known to have strong antioxidant and anticarcinogenic properties.18 Carotene and vitamin C, in particular, have been inversely related to laryngeal cancer risk,19, 20, 21, 22, 23 although the evidence for the potential favourable effect of any specific micronutrient is less consistent than that for vegetables and fruit. The key message of this study, moreover, is that the variety of fruit and vegetables, and hence a diet rich in fruit and vegetables, rather than any specific type of fruit and vegetable exerts a favourable effect on laryngeal cancer risk. This study points therefore to a role of dietary pattern on laryngeal cancer carcinogenesis rather than of specific foods and nutrients.

Although meat itself has not been consistently related to laryngeal cancer risk,1 the meat diversity effect could be due to its content of fat, found to be positively related to laryngeal cancer risk in a few studies.23, 24

The associations with vegetables, fruit and meat diversity were consistent across strata of age, tobacco smoking and alcohol drinking, thus showing that they are independent of the two major risk factors for laryngeal cancer.

Among the possible limitations of the present study, there is the use of hospital controls, whose dietary habits may differ from those of the general population.17 However, we excluded from the control group all diagnoses involving any long-term changes in diet. The comparable catchment areas for cases and controls, and the almost complete participation are reassuring against possible selection bias. Bias in the recall of food intake by cases should be small given the limited knowledge and attention paid in the population to the possible relation between diet and laryngeal cancer. Given the same interview settings, information provided by hospital controls should have a good comparability with that by cases. A reproducibility study conducted in this population showed a satisfactory reliability of dietary information from subjects interviewed at home with that provided during their original interview in the hospital.25 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. Patients with severe conditions with sudden onset may also have problems in recalling dietary consumption. However, separate comparisons of cases with controls from major diagnostic categories (e.g., traumas, other orthopedic, surgical, and miscellaneous other conditions) gave comparable results.

Among other strengths of our study there are the use of a valid and reproducible FFQ,14, 15 and the allowance for energy intake and for other major recognized confounding factors such as tobacco, alcohol, and education.

In conclusion, the present findings that fruit and vegetable diversity are related to a decreased risk of laryngeal cancer risk, and add epidemiological support to the dietary guidelines recommending a more varied diet. 26, 27 Further studies analyzing eating patterns that may influence laryngeal cancer risk are also needed in addition to studies of individual foods and nutrients.

Conflict of Interest Statement 

None declared.