Tobacco smoking and the risk of upper aero-digestive tract cancers: A reanalysis of case-control studies using spline models

Although tobacco smoking has long been recognized as a major risk factor for cancer of the upper aero-digestive tract (UADT, i.e., oral cavity, pharynx, larynx, and oesophagus), very few studies have provided estimates of the effect of very low tobacco consumption. Step-functions have been the common statistical methods for risk estimates, but the choice of reference category and of interval cutpoints influence the results, especially when data are sparse. In the present analysis, the dose-response relationship between UADT cancers and tobacco smoking was evaluated through logistic regression spline models. We included 1,241 UADT male cases and 2,835 male controls pooled from a large series of case-control studies conducted in northern Italy and in the Swiss Canton of Vaud during the last 2 decades. For cancers of the pharynx, larynx and oesophagus, the risk steadily increased with number of cigarettes/day. The risk of oral, pharyngeal and oesophageal cancers was significantly higher in smokers than in nonsmokers beginning with as low as 2 cigarettes/day. The effect of tobacco smoking at low levels seemed less evident for laryngeal cancer since the raise in risk begun with 6 cigarettes/day. In conclusion, for all the examined UADT sites, a monotonic dose-response relationship between cancer risk and cigarette smoking emerged. The excess of risk among people smoking 2 cigarettes/day highlights the absence of any harmless level for cigarette smoking, and it further supports the need of public health programs against tobacco smoking.     

Cigar smoking in men and risk of death from tobacco-related cancers

BACKGROUND: Cigar consumption in the United States has increased dramatically since 1993, yet there are limited prospective data on the risk of cancer associated with cigar smoking. We examined the association between cigar smoking and death from tobacco-related cancers in a large, prospective cohort of U. S. men. METHODS: We used Cox proportional hazards models to analyze the relationship between cigar smoking at baseline in 1982 and mortality from cancers of the lung, oral cavity/pharynx, larynx, esophagus, bladder, and pancreas over 12 years of follow-up of the American Cancer Society's Cancer Prevention Study II cohort. A total of 137 243 men were included in the final analysis. Women were not included because we had no data on their cigar use. We excluded men who ever smoked cigarettes or pipes and adjusted all rate ratio (RR) estimates for age, alcohol use, and use of snuff or chewing tobacco. RESULTS: Current cigar smoking at baseline, as compared with never smoking, was associated with an increased risk of death from cancers of the lung (RR = 5.1; 95% confidence interval [CI] = 4.0-6.6), oral cavity/pharynx (RR = 4.0 [95% CI = 1.5-10.3]), larynx (RR = 10.3 [95% CI = 2.6-41.0]), and esophagus (RR = 1.8; 95% CI = 0.9-3.7). Although current cigar smokers overall did not appear to be at an increased risk of death from cancer of the pancreas (RR = 1.3; 95% CI = 0.9-1.9) or bladder (RR = 1.0; 95% CI = 0.4-2.3), there was an increased risk for current cigar smokers who reported that they inhaled the smoke (for pancreas, RR = 2.7; 95% CI = 1.5-4.8; for bladder, RR = 3.6; 95% CI = 1.3-9.9). CONCLUSIONS: Results from this large prospective study support a strong association between cigar smoking and mortality from several types of cancer.     

Hand-rolled cigarette smoking and risk of cancer of the mouth, pharynx, and larynx.

A case-control study, involving 205 patients with cancer of the mouth, pharynx, and larynx and 273 control subjects with conditions considered not related to tobacco or alcohol consumption, was performed in Montevideo, Uruguay, between January 1988 and December 1990. Smokers of hand-rolled cigarettes showed an increased risk of cancer of the mouth and pharynx (odds ratio [OR] = 2.5; 95% confidence limit = 1.2-5.2) when compared with smokers of manufactured cigarettes. Also, the risk of laryngeal cancer was greater among smokers of hand-rolled cigarettes (OR = 2.7; 95% confidence limit = 1.3-5.7) as compared with smokers of commercial cigarettes.     

Light alcohol drinking and cancer: a meta-analysis

BackgroundThere is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day).Patients and methodsWe evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010.ResultsWe included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06–1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09–1.56) and female breast cancer (RR = 1.05; 95% CI 1.02–1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors.ConclusionsLight drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.     

Comparative epidemiology of tobacco-related cancers

In a retrospective study, interviews were obtained with 3,716 patients with histologically proven cancer of the lung (Kreyberg types I and II), mouth, larynx, esophagus, or bladder and with over 18,000 controls. For each of these cancers, the relative risk of both male and female present smokers increased with the quantity smoked and the duration of the habit. The strongest increase occurred for cancer of the lung and larynx, and the least increase occurred for cancer of the esophagus and bladder. For exsmokers the risk decreased with years of cessation. The risk for mouth cancer of pipe and cigar smokers who inhaled much less than cigarette smokers was less than that of the latter and increased with the quantity smoked. The risk of mouth, larynx, and esophagus cancer among smokers increased with the quantity of alcohol consumed. Greater smoking habits and lesser cessation rates were noted among lower socioeconomic groups, suggesting that these groups will bear an ever increasing proportion of the burden of tobacco-related cancer.     

Impact of long-term filter cigarette usage on lung and larynx cancer risk: a case-control study.

A case-control study was conducted among 1.034 white male and female hospital patients with histologically proved lung cancer (Kreyberg type l) or larynx cancer. After adjustment for duration of the smoking habit, inhalation, and butt length, relative risks of developing lung or larynx cancer were consistently lower among long-term smokers of filter cigarettes than among smokers of nonfilter cigarettes, irrespective of quantity smoked. Relative risks in all groups declined with increased years of smoking cessation. The observed risk reduction among current smokers of filter cigarettes was consistent with that expected, considering that these persons had smoked the older high-tar nonfilter cigarettes for a large proportion of their lives.     

Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial

BACKGROUND: Although smoking and alcohol consumption are the major risk factors for upper aerodigestive tract cancers, observational studies indicate a protective role for fruits, vegetables, and antioxidant nutrients. METHODS: The authors examined whether daily supplementation with 50 mg dl alpha-tocopheryl acetate and/or 20 mg beta-carotene reduced the incidence of or mortality from oral/pharyngeal, esophageal, and laryngeal cancers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a double-blind, placebo-controlled primary prevention trial conducted in southwestern Finland. A total of 29,133 male smokers, aged 50-69 years and free of cancer at baseline, were randomized in a 2 x 2 factorial design to the supplementation regimen for 5-8 years (median, 6.1 years). Incident cancers of the oral cavity and pharynx (n = 65), esophagus (n = 24), and larynx (n = 56) were identified through the Finnish Cancer Registry. Intervention effects were assessed using survival analysis and proportional hazards models. RESULTS: There was no effect of either agent on the overall incidence of any upper aerodigestive tract cancer. For larynx, however, exploratory subgroup analyses were suggestive of a protective effect of beta-carotene supplementation on the incidence of early stage malignancies (stage I, relative risk [RR], 0.28, 95% confidence interval [CI]: 0.10-0.75). Neither agent affected mortality from these neoplasms. CONCLUSIONS: The results do not provide support for a protective effect of vitamin E or beta-carotene supplementation on upper aerodigestive tract cancers, although beta-carotene supplementation may impact the incidence of some subtypes of laryngeal tumors.     

Second Primary Cancer Following Laryngeal Cancer with Special Reference to Smoking Habits

The risk of developing a second primary cancer following laryngeal cancer was estimated by following-up 472 male laryngeal cancer patients for an average of 8.6 years by means of record linkage to the Osaka Cancer Registry. Of these patients, 115 developed a second cancer other than laryngeal cancer, whereas the expected number derived from the incidence rates among Osaka residents was 51.4 (relative risk (RR) = 2.2, 95% confidence interval = 1.85 2.69). Cumulative risk of developing a second primary cancer was estimated to be 31.1% at 15 years after laryngeal cancer. By site, the risks were significantly increased for tobacco-related cancers, RR = 24.5, 6.1 and 2.3 for cancers of the oral cavity & pharynx, esophagus and lung, respectively. Also, the risks were higher among heavy smokers for cancer of the oral cavity & pharynx and esophagus than among light smokers. No adverse effects of radiotherapy for laryngeal cancer on the development of thyroid cancer, lymphoma and leukemia were observed. The present study suggests the necessity of following-up laryngeal cancer patients over a long period in order to enable the early detection of tobacco-related cancer.     

Second primary cancer following laryngeal cancer with special reference to smoking habits.

The risk of developing a second primary cancer following laryngeal cancer was estimated by following-up 472 male laryngeal cancer patients for an average of 8.6 years by means of record linkage to the Osaka Cancer Registry. Of these patients, 115 developed a second cancer other than laryngeal cancer, whereas the expected number derived from the incidence rates among Osaka residents was 51.4 (relative risk (RR) = 2.2, 95% confidence interval = 1.85-2.69). Cumulative risk of developing a second primary cancer was estimated to be 31.1% at 15 years after laryngeal cancer. By site, the risks were significantly increased for tobacco-related cancers, RR = 24.5, 6.1 and 2.3 for cancers of the oral cavity & pharynx, esophagus and lung, respectively. Also, the risks were higher among heavy smokers for cancer of the oral cavity & pharynx and esophagus than among light smokers. No adverse effects of radiotherapy for laryngeal cancer on the development of thyroid cancer, lymphoma and leukemia were observed. The present study suggests the necessity of following-up laryngeal cancer patients over a long period in order to enable the early detection of tobacco-related cancer.     

Prospective investigation of the cigarette smoking-head and neck cancer association by sex

BACKGROUND: Men are approximately 3 times more likely to develop squamous cancers of the head and neck (oral cavity, pharynx, and larynx) than women. Very few prospective studies have examined the association between cigarette smoking and cancers of the head and neck in women, even though the rates of smoking in women are increasing rapidly worldwide. METHODS: The association between cigarette smoking and head and neck cancer was investigated in 476,211 participants, aged 50-71 years, of the National Institutes of Health/American Association of Retired Persons (NIH-AARP) diet and health study by using age-standardized incidence rates and hazard ratios from Cox models adjusted for other risk factors for these cancers. RESULTS: Over the course of follow-up (1995 through 2000), 584 men and 175 women were diagnosed with head and neck cancer. Nonsmoking (24.4), former smoking (36.9), and current smoking (147.3) men had higher rates of incident head and neck cancer per 100,000 person-years of follow-up than women did in each equivalent category of cigarette use (non: 4.8; former: 17.2; current: 75.7). The hazard ratios associated with smoking were significantly larger in women (12.96; 95% confidence interval [CI], 7.81-21.52) than in men (5.45, 95% CI, 4.22-7.05; P for interaction: <.001) for head and neck cancer overall and also for the 3 subsites (oral cavity, oro-hypopharynx, and larynx) examined in stratified analyses. Ever-smoking accounted for 45% of head and neck cancers in men and 75% in women, assuming causality. CONCLUSIONS: Cigarette smoking is a strong risk factor for head and neck cancer in both men and women. Incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men.     

Rauchen, Passivrauchen und Krebserkrankungen

Tobacco smoking is the most important avoidable cause of cancer. About one third of all cancer deaths in many Western countries can be attributed to smoking. Lung cancer is the most prominent tobacco-induced cancer. In Europe, about 90% of all lung cancer deaths among men and 60% among women are caused by smoking. Duration of smoking is the strongest determinant of lung cancer. Risk also increases in proportion to the number of cigarettes smoked. Stopping smoking reduces the risk. The younger the age at cessation, the greater the benefit. An updated evaluation of epidemiological studies by the International Agency for Research on Cancer (IARC) concluded that, in addition to cancer of the lung, oral cavity, oro- and hypopharynx, larynx, pancreas, renal pelvis, urinary bladder and esophagus (squamous cell carcinoma), there is sufficient evidence for a causal association between smoking and cancers of the nasal and sinonasal cavities, nasopharynx, esophagus (adenocarcinoma), stomach, liver, uterine cervix, as well as myeloid leukemia, and renal cancer. Among never-smokers, exposure to environmental tobacco smoke is an established causal risk factor for lung cancer.     

Smoking, alcohol, diet, dentition and sexual practices in the epidemiology of oral cancer in Poland.

The effect of smoking, drinking, diet, dental care and sexual habits on the risk of oral and pharyngeal cancer was investigated in a case-control study conducted in Warsaw, Poland. The study comprised 122 patients (including 44 females) aged 23-80 years with histologically confirmed cancer of oral cavity and pharynx. Controls were 124 subjects (including 52 females) admitted to the hospital for different non-neoplastic conditions unrelated to tobacco and alcohol consumption, with frequency matched to cases by age and sex. Smoking and drinking were strongly associated with an increased risk of oral cancer. Among consumers of both products, risks of oral cancer tended to combine in a multiplicative fashion and were increased more than 14-fold among those who consumed more than 15 cigarettes and seven or more drinks per day. Cessation of smoking was associated with reduced risk of this cancer. The risks varied by type of cigarettes smoked, being lower among those consuming filtered cigarettes only (OR = 1.6) than nonfilter (OR = 6.5) or mixed (OR = 4.2) cigarettes. High fruit intake was associated with significantly decreased risk (OR = 0.4) with the strongest significant inverse association found for fruit juices and citrus fruits ( < 0.01). After adjustment for tobacco smoking and alcohol drinking, poor dentition as evidenced by missing teeth, frequency of dental check-ups and frequency of teeth brushing emerged as a strong risk factor. Number of missing teeth and frequency of dental check-ups and frequency of tooth brushing showed increased ORs of 9.8, 11.9 and 3.2, respectively. Denture wearing did not affect oral cancer risk. No differences were detected in sexual practices (including oral sex and intercourse with prostitutes). In terms of attributable risk, smoking accounted for 57% of oral cancer cases in Poland, alcohol for 31% and low fruit intake for 12%. Attributable risks for low frequency of tooth brushing and dental check-ups were 56% and 47%, respectively. In conclusion, smoking and drinking cessation and increase of fresh fruit intake are likely to be effective preventive measures against oral cancer. These findings indicate also that poor oral hygiene may be an independent risk factor.     

Different impact from betel quid, alcohol and cigarette: risk factors for pharyngeal and laryngeal cancer

The risks of betel quid chewing with or without tobacco, alcohol drinking and cigarette smoking have been well explored in the oral cavity but not in the pharynx and larynx. We conducted a case-control study to investigate the association of these three risk factors to cancers of the pharynx and larynx in Taiwan. A total cases of 148 pharyngeal cancer, 128 laryngeal cancer and 255 hospital controls, all men, were recruited. Betel quid chewing was a significant independent risk factor (adjusted odds ratio [aOR] = 7.7; 95% confidence interval [CI] = 4.1-15.0) similar to that of alcohol drinking (aOR = 6.6; 95% CI = 3.5-13.0) for pharyngeal cancer, but not for laryngeal cancer (aOR = 1.3; 95% CI = 0.7-2.5) on which cigarette smoking (aOR = 7.1) exerts a stronger significant independent risk than alcohol drinking (aOR = 3.8). For pharyngeal cancers, chewers who consumed >20 quid/day, chewed with inflorescence in the quid or swallowed the betel quid juice were at higher risks; significant dose-response effects were found in daily quantity of drinking and chewing, and cumulative quantity of drinking. Synergistic effects from the 3 risk factors existed both on the pharynx (aOR = 96.9) and the larynx (aOR = 40.3), and attributed for 93.1% and 92.9% respectively. Our study is the first evidence to show that betel quid chewing without tobacco has different impact on the pharynx (digestive tract) and the larynx (airway), and supports the concept that exposure quantity and direct mucosal contact with the betel quid juice may contribute to carcinogenesis. Our results show an important insight into the impact of betel quid chewing on other sites of the digestive tract other than the oral cavity.     

Effects of tobacco smoking on cancer and cardiovascular disease in urban black South Africans

Demographic and lifestyle information from 9690 black patients diagnosed with cancer or cardiovascular disease was collected in an ongoing case-control study in Johannesburg, South Africa. Compared to never smokers, the odds ratio (OR) for lung cancer among current smokers was 16.3 (95% confidence interval (CI), 9.6-27.6) for men and 6.4 (95% CI, 4.0-10.4) for women. The corresponding OR for other smoking-related cancers was 4.6 (95% CI, 3.7-5.7) among men and 1.9 (95% CI, 1.6-2.2) among women, and for cardiovascular disease, 3.4 (95% CI, 2.1-5.4) among men and 1.5 (95% CI, 1.1-2.1) among women. Risks were higher among smokers than former smokers, and all risk estimates increased with increasing levels of smoking duration and intensity. Non-electric domestic fuel was associated with approximately 60% increase in the risk of smoking-related cancer, but not cardiovascular disease. Risks for cancers of cervix, oesophagus, oral cavity/pharynx, stomach, larynx, pancreas and anogenital region, as well as squamous cell carcinoma of skin were all significantly higher among current than never-smokers, with ORs ranging from 1.5 for cervix (95% CI, 1.2-1.8) to 14.7 for larynx (95% CI, 7.2-30). The risks of tobacco-related disease reported here are similar to that currently observed in Western countries, even though cigarette consumption is relatively low in this population.     

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.     

Diet and risk of cancer of the upper aerodigestive tract--I. Foods

In order to examine the risks of cancer of the upper aerodigestive tract associated with food groups, a case-control study was conducted in Uruguay in the period January 1996-December 1997. All patients afflicted with cancer of the oral cavity, pharynx larynx, and esophagus, were included in the study. Cases were frequency matched with hospitalized patients on age, sex, residence, and urban/rural status. A strong association with red meat intake was observed (OR 2.4, 95% CI 1.2-4.8), whereas vegetables fruits and legumes were associated with an inverse association (OR for fruits 0.3, 95% CI 0.2-0.6). Salted meat, a possible source of nitrosamines, was associated with an increased risk of 60% for esophageal cancer. Possible mechanisms for these findings are discussed.     

Smoking and mortality from esophageal cancer in China: a large case-control study of 19,734 male esophageal cancer deaths and 104,846 living spouse controls

An innovative population-based case-control study was conducted in a national mortality survey to assess the hazards of tobacco use on esophageal cancer among Chinese men. Cases were 19,734 males aged 35 years or older, who died of esophageal cancer during 1986-1988. Controls were 104,846 male living spouses of the same age when their wife died (of any cause) during the same period in the same county or city. The absolute esophageal cancer death rates were higher in smokers than those in nonsmokers in all geographical groups. The relative risks for esophageal cancer were 1.88 (95% CI: 1.73-2.05) and 1.39 (95% CI: 1.28-1.50) in urban and rural men, respectively, after adjustment for other relevant covariates including age group (5 years) and locality. When the calculation was restricted to men aged 35-69, the risk ratios for current cigarette smokers increased significantly with increasing number of cigarettes smoked daily and duration of smoking. Tobacco use, in any form, is an important risk factor for esophageal cancer in Chinese men. Selecting living spouses as controls is a unique and useful approach in the design of case-control studies of cigarette smoking.     

Risk of tobacco-related multiple primary cancers in Bavaria, Germany

ABSTRACT: BACKGROUND: With the prospect of increasing prevalence of cancer, the issue of multiple primary cancers becomes more relevant. The aim of this study was to estimate the risk of developing a tobacco-related subsequent primary cancer (TRSPC) in persons with a tobacco-related first primary cancer (TRFPC) compared with the general population in Bavaria, Germany. METHODS: Using data from the Population-Based Cancer Registry Bavaria, we analyzed TRFPC and TRSPC diagnosed in Bavaria between 2002 and 2008 to estimate the relative and absolute risk of developing TRSPC using standardized incidence ratios (SIR) and excess absolute risks (EAR). RESULTS: 121,631 TRFPC in men and 75,886 respective cancers in women were registered, which in 2.5% of male and 1.2% of female cancer patients were followed by at least one TRSPC. In both males and females, the highest increased risks compared to the general population were found within the group of cancer in the mouth/pharynx, oesophagus, larynx, and lung/bronchus. CONCLUSIONS: With respect to cancer in the mouth/pharynx, oesophagus, larynx, lung/bronchus, kidney, urinary bladder and urinary tract, smoking was confirmed as a shared risk factor based on our finding of mutually significantly increased risks of TRSPC. The results of this study illustrate the importance of smoking cessation and of continued follow-up care especially of smokers with the aforementioned TRFPC to detect TRSPC at an early stage.     

Risk factors for oral and pharyngeal cancer in never smokers

Information on the etiology of oral and pharyngeal cancer in never smokers should help us to understand and quantify risk factors for the disease in the absence of the residual confounding and interaction by smoking. Out of a total of 528 cases with histologically confirmed incident cancers of the oral cavity and pharynx, 42 (10 men and 32 women) who described themselves as lifelong non-smokers were considered. Controls were 864 lifelong non-smokers (442 men and 422 women) admitted to hospital for acute, non-neoplastic, non-alcohol-related conditions. The major risk factor for cancer of the oral cavity and pharynx in never smokers was alcohol consumption (mainly wine) with an odds ratio (OR) about three-fold higher in drinkers than non-drinkers. A direct relation was also found for the duration of the habit, with an OR of 3.6 (95% confidence intervals, CI, 1.2-11.2) for drinking for 35 years or longer. Among the few selected indicator foods considered, a direct association was found with butter (OR 2.7, 95% CI 1.4-5.1 for high intake compared to low), and a non-significant inverse association with carrots (OR 0.6, 95% CI 0.3-1.3) and fresh fruit (OR 0.7, 95% CI 0.3-1.6) for the highest tertile of intake compared to the lowest. Thus, even in the absence of smoking, reducing alcohol and saturated fat intake and increasing fruit and carrot consumption may have favorable effects on oral and pharyngeal cancer risk.