Aspirin use and cancers of the upper aerodigestive tract

The role of aspirin on the risk of cancers of the upper aerodigestive tract was investigated in the combined data of three Italian case-control studies, including 965 cases and 1779 hospital controls. The odds ratio was 0.33 for users of > or = 5 years, and 0.51 for > or = 5 years since first use.     

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.     

Cessation of smoking and drinking and the risk of laryngeal cancer

A case-control study was conducted in Italy and Switzerland between 1992 and 2000 on 527 cases of laryngeal cancer and 1,297 hospital controls. The risk of laryngeal cancer steadily decreased from 3 years after stopping smoking. Some decline in risk was observed only 20 years or more after stopping drinking.     

Occupation and risk of upper aerodigestive tract cancer: the ARCAGE study

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry.     

Alcohol drinking outside meals and cancers of the upper aero-digestive tract

In our integrated series of case-control studies conducted in Italy and Switzerland (324 oral, 397 pharyngeal, 271 oesophageal, 506 laryngeal cancers and 3,263 controls), individuals who also drank alcoholic beverages outside meals showed an increased risk compared to those who drank at meals only. At any alcohol intake level, subjects also drinking between meals showed a more elevated risk of developing an upper aero-digestive tract cancer than subjects drinking only at meals. After adjustment for potential covariates, and, after allowance for the number of daily drinks to adjust for different alcohol-intake levels, the odds ratios for subjects reporting drinking outside meals were 1.5 (95% confidence interval [CI]: 1.0-2.2) for oral, 1.8 (95% CI: 1.3-2.5) for pharyngeal, 1.7 (95% CI: 1.2-2.5) for oesophageal and 1.2 (95% CI: 0.9-1.7) for laryngeal cancers. Our findings show that drinking pattern with respect to food consumption may influence alcohol carcinogenesis in the upper digestive and respiratory tract. An "alcohol washing effect" by chewing and swallowing is suggested.     

Cigarette tar yield and risk of upper digestive tract cancers: case-control studies from Italy and Switzerland.

BACKGROUND: Tobacco smoking is one of the main risk factors for oral, pharyngeal and oesophageal cancers in developed countries. Information on the role of the tar yield of cigarettes in upper digestive tract carcinogenesis is sparse and needs to be updated because the tar yield of cigarettes has steadily decreased over the last few decades. PATIENTS AND METHODS: We analysed two case-control studies, from Italy and Switzerland, conducted between 1992 and 1999, involving 749 cases of oral and pharyngeal cancer and 1770 controls, and 395 cases of squamous-cell oesophageal carcinoma and 1066 matched controls. Odds ratios (ORs) were estimated by unconditional multiple logistic regression models, including terms for age, sex, study centre, education and alcohol consumption. RESULTS: Based on the brand of cigarettes smoked for the longest time, the multivariate ORs for current smokers compared with never smokers were 6.1 for <20 mg and 9.8 for >or=20 mg tar for oral and pharyngeal neoplasms, and 4.8 and 5.4 for oesophageal cancer, respectively. For the cigarette brand smoked in the previous six months, the ORs for >or=10 mg compared with <10 mg were 1.9 for cancer of the oral cavity and pharynx and 1.8 for oesophageal cancer, after allowance for number of cigarettes and duration of smoking. CONCLUSIONS: The present study confirms the direct relationship between the tar yield of cigarettes and upper digestive tract neoplasms, and provides innovative information on lower tar cigarettes, which imply reduced risks compared with higher tar ones. However, significant excess risks were observed even in the lower tar category, thus giving unequivocal indications for stopping smoking as a priority for prevention of upper digestive tract neoplasms.     

Type of cigarettes and cancers of the upper digestive and respiratory tract

The relationship between type of cigarettes smoked and the risk of cancer of upper digestive and respiratory sites was investigated in a case-control study conducted in Northern Italy on 291 males with cancer of the oral cavity or pharynx, 288 with cancer of the esophagus, 162 with cancer of the larynx, and 1,272 control subjects in hospital for acute conditions unrelated to tobacco or alcohol consumption. Using a distinction based on tar-yield or the brand smoked for the longest time (<22 mg, low to medium tar; 22 mg, high tar), the multivariate relative risks among ever-smokers were 8.5 for low/medium and 16.4 for high tar cigarettes for oral and pharyngeal neoplasms, 3.3 and 7.8 for esophageal, and 4.8 and 7.1 for laryngeal cancers. The differences according to type of cigarettes were similar in proportional terms, and hence larger in absolute terms, when analysis was restricted to current smokers only. Thus, these data provide further quantitative evidence on the importance of type of cigarette smoked on the risk of upper-digestive and respiratory tract cancers and have important public health implications.Drs La Vecchia, D'Avanzo and Negri are at the Istituto di Richerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy. Dr La Vecchia is also at the Institute of Social and Preventive Medicine, University of Lausanne, 1005 Lausanne, Switzerland. Drs Bidoli, Barra, Talamini and Franceschi are in the Aviano Cancer Center, 33081 Aviano, Prodenone, Italy. Reprint requests should be addressed to Dr La Vecchia at the Istituto di Ricerche Farnacologiche. This work was conducted within the framework of the National Research Council (CNR), Applied Projects Oncology (Contract No. 87.01544.44) and Risk Factors for Disease, with contributions from the Italian Association for Cancer Research and the Italian League against Tumours, Milan.     

Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy

Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case-control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8-20.3) than among women (OR = 4.2, CI 3.5-5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0-19, 20-39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6-4.2], 4.1 [CI 3.1-5.6]) and women (OR = 1.0, 2.7 [CI 1.7-4.1], 3.3 [CI 1.9-5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men.     

Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States)

Objective: This study evaluated the joint effects of tobacco smoking and alcohol consumption on the risk of second primary tumors (SPT) in patients with early-stage head and neck squamous cell carcinoma (HNSCC). Methods: Data are presented for 1181 patients enrolled in a placebo-controlled chemoprevention trial of 13-cis-retinoic acid. Nearly 17% of patients presented with a SPT. The log rank test and Cox proportional hazards model were used to examine risk factors for SPT development. Results: After adjusting for the time from the index diagnosis to randomization, age at diagnosis, stage, and site of the primary cancer, the factors that emerged as simultaneous predictors of SPT development were continued smoking and alcohol intake after the index diagnosis. Increased SPT risk was associated with older age (RR = 2.1; 95% CI 1.5–2.8); stage II diagnosis (RR = 1.5; 95% CI 1.1–2.1); index diagnosis of pharyngeal cancer (RR = 1.6; 95% CI 1.1–2.5); current smoking at registration (RR = 2.1; 95% CI 1.3–3.6) and continued alcohol consumption post-diagnosis (RR = 1.3; 95% CI 1.0–1.7). Conclusion: Important associations exist between SPT development and continued smoking and alcohol consumption after treatment for HNSCC.     

Morning chronotype and digestive tract cancers: Mendelian randomization study

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome-wide significance level (P < 5 × 10⁻⁸) were used as instrumental variables from a genome-wide meta-analysis of 449 734 individuals. Summary-level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta-analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90-0.98), stomach cancer (OR 0.84, 95% CI: 0.73-0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87-0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers.     

Cigarette smoking and colorectal cancer risk in Germany: a population-based case-control study

Studies have shown fairly consistent positive relationships between smoking and risk of colorectal adenomas, but have yielded inconsistent results for colorectal cancer. Issues relating to the duration, cumulative dose of smoking and the effect of smoking cessation on colorectal cancer risk still need clarification. In a population-based case-control study in Germany, we recruited 540 incident cases of colorectal cancer and 614 controls matched to cases by sex, 5-year age groups and county of residence from January 2003 to June 2004. Subjects were aged>or=30 years, and provided information on risk factors of colorectal cancer, including lifetime cigarette smoking habits, in personal interviews. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression models, adjusting for potential confounders. Compared with nonsmokers, there was an increased risk for smoking for >or=30 years (OR: 1.25, 95% CI: 0.90-1.75) and a significant risk increase for >or=40 pack-years of smoking (OR: 1.92, 95% CI: 1.13-3.28). Stratification by sex yielded higher risk estimates among females than that among males, with adjusted ORs of 3.5 (95% CI: 1.29-9.52) and 1.15 (0.69-1.91) for women and men, respectively, following >or=30 pack-years of smoking (pinteraction=0.18). Among smokers, risk reduction was observed after >or=20 years of quitting smoking and was significant for >or=40 years (OR: 0.46; 95% CI: 0.21-0.98), when compared to current smokers (p for linear trend=0.05). This study supports the hypothesis that smoking for a long duration at a high cumulative dose increases the risk for colorectal cancer, particularly among women, and suggests that there is risk reduction after longterm smoking cessation.     

Flavonoids and ovarian cancer risk: A case-control study in Italy

Flavonoids belong to a vast group of polyphenols widely distributed in all foods of plant origin. Because of their antioxidant, antimutagenic and antiproliferative properties, they have been hypothesized to contribute to the favorable effects of fruit and vegetables against cancer. The aim of this study is to investigate the relation of 6 classes of flavonoids (flavan-3-ols, flavanones, flavonols, flavones, anthocyanidins and isoflavones) with ovarian cancer risk, using data from a multicentric case-control study conducted in Italy between 1992 and 1999. The study included 1,031 cases with incident, histologically confirmed epithelial ovarian cancer and 2,411 controls admitted for acute, nonneoplastic conditions to major hospitals in the same catchment areas. In logistic regression models including study center, education, year of interview, parity, oral contraceptive use and family history of ovarian or breast cancer or both, an inverse relation with significant trend in risk was found between ovarian cancer and flavonols [odds ratio (OR), 0.63; 95% confidence intervals (CI) 0.47-0.84] as well as isoflavones (OR, 0.51; 95% CI, 0.37-0.69), comparing the highest versus the lowest quintile. Further adjustment for fruit and vegetable intake did not modify these associations, suggesting that isoflavones and flavonols may have a distinct role in explaining the effect of fruit and vegetable against ovarian cancer. On the basis of our findings and the relevant literature, we infer that isoflavones, and perhaps flavonols, may have favorable effects with respect to ovarian cancer risk.     

History of cirrhosis and risk of digestive tract neoplasms.

BACKGROUND: Cirrhosis is strongly related to liver cancer. Data on the possible association between cirrhosis and risk at other cancer sites are scanty. PATIENTS AND METHODS: We analysed data from a network of case-control studies conducted in Italy between 1983 and 1997, including patients with cancers of the oral cavity and pharynx (520), oesophagus (405), stomach (731), colon (943), rectum (613), liver (425), gallbladder (63) and pancreas (395). The controls were 4297 patients admitted to hospitals for acute non-neoplastic conditions. RESULTS: After strict allowance for alcohol drinking, tobacco smoking and history of hepatitis, the multivariate odds ratios for a history of cirrhosis were 4.7 [95% confidence interval (CI) 2.2-9.8] for neoplasms of the oral cavity and pharynx, 2.6 (95% CI 1.2-5.7) for the oesophagus, 1.0 (95% CI 0.4-2.5) for the stomach, 1.0 (95% CI 0.4-2.4) for the colon, 1.7 (95% CI 0.7-4.1) for the rectum, 20.5 (95% CI 12.3-34.2) for the liver, 2.1 (95% CI 0.3-16.8) for the gallbladder and 0.9 (95% CI 0.3-3.0) for the pancreas. CONCLUSIONS: Our study confirms and further quantifies the increased risk of liver cancer in cirrhotic patients and is compatible with an increased risk of oral, pharyngeal and oesophageal cancers.     

Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection

Background:

Immunodeficiency and AIDS-related pulmonary infections have been suggested as independent causes of lung cancer among HIV-infected persons, in addition to smoking.

Methods:

A total of 68 lung cancers were identified in the Swiss HIV Cohort Study (SHCS) or through linkage with Swiss Cancer Registries (1985–2010), and were individually matched to 337 controls by centre, gender, HIV-transmission category, age and calendar period. Odds ratios (ORs) were estimated by conditional logistic regression.

Results:

Overall, 96.2% of lung cancers and 72.9% of controls were ever smokers, confirming the high prevalence of smoking and its strong association with lung cancer (OR for current vs never=14.4, 95% confidence interval (95% CI): 3.36–62.1). No significant associations were observed between CD4+ cell count and lung cancer, neither when measured within 1 year (OR for <200 vs ⩾500=1.21, 95% CI: 0.49–2.96) nor further back in time, before lung cancer diagnosis. Combined antiretroviral therapy was not significantly associated with lung cancer (OR for ever vs never=0.67, 95% CI: 0.29–1.52), and nor was a history of AIDS with (OR=0.49, 95% CI: 0.19–1.28) or without (OR=0.53, 95% CI: 0.24–1.18) pulmonary involvement.

Conclusion:

Lung cancer in the SHCS does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking.     

Multiple primary squamous cell carcinomas in the upper digestive tract

Multiple squamous cell carcinomas are common and patients carry a constant and excessive risk of developing a new cancer at any time (13-21 X the normal). Among 6,203 cases of primary squamous carcinoma of the upper digestive tract, 648 patients (10.4%) developed two or more independent tumors. Altogether, 761 additional malignancies were observed, with up to five cancers being seen in individual patients. There were 279 patients with a prior or synchronous cancer and 409 patients who developed 462 metachronous tumors. There was a substantial risk for developing a second primary cancer in the upper aerodigestive tract. Overall the observed to expected ratio was 2.48, specifically 2.32 for males and 2.89 for females.     

Smoking and drinking cessation and the risk of oesophageal cancer

In a case-control study from Italy and Switzerland with 404 oesophageal cancer cases and 1070 hospital controls, the risk of oesophageal cancer declined with time since cessation of smoking or drinking, and was significantly reduced (odds ratio = 0.11) 10 or more years after cessation of both habits.     

Association of NAT2 and smoking in relation to breast cancer incidence in a population-based case-control study (United States)

Objective: To evaluate the potential interaction between N-acetyltransferase 2 (NAT2) and smoking in breast cancer incidence. Methods: The data are derived from a population-based case–control study of women aged 20–69 years who were residents of Massachusetts or Wisconsin during 1997–1998. Incident cases of invasive breast cancer were identified through state tumor registries and age-similar controls were selected at random from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors including smoking history. Women provided oral mucosal DNA through the mail for genetic studies. Results: A total of 791 cases and 797 controls were included in the analysis. Overall, smoking was modestly associated with breast cancer risk (multivariate odds ratio (OR) for ever smoking: 1.37; 95% confidence interval (CI): 1.12–1.69), and there was a trend in risk for greater pack-years of smoking among postmenopausal women (p for trend = 0.02). Overall, NAT2 was not related to invasive breast cancer (multivariate OR: 1.11; 95% CI: 0.90–1.36). Associations of smoking with breast cancer tended to be somewhat stronger among the women with the slow acetylator genotype for NAT2: when compared to those who never smoked and were rapid acetylators, the OR for ever smoking was 1.50 (95% CI: 1.11–2.02) in slow acetylators, and OR: 1.24 (95% CI: 0.91–1.70) in rapid acetylators. However, tests for multiplicative interaction were not significant in case–control comparisons, or in case-only analyses. Conclusion: Results of the study are compatible with the majority of previous studies that indicate little or no association of NAT2, smoking, or their interaction with the occurrence of breast cancer.     

Food groups and renal cell carcinoma: a case-control study from Italy

Although nutrition and diet have been related to renal cell carcinoma (RCC), the role of specific foods or nutrients on this cancer is still controversial. We evaluated the relation between a wide range of foods and the risk of RCC in an Italian case-control study including 767 patients (494 men and 273 women) younger than 79 years with incident, histologically confirmed RCC, and 1,534 controls (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, not related to long term diet modifications. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcohol drinking, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major confounding factors. A significant direct trend in risk was found for bread (OR = 1.94 for the highest versus the lowest intake quintile), and a modest excess of risk was observed for pasta and rice (OR = 1.29), and milk and yoghurt (OR = 1.27). Poultry (OR = 0.74), processed meat (OR = 0.64) and vegetables (OR = 0.65) were inversely associated with RCC risk. No relation was found for coffee and tea, soups, eggs, red meat, fish, cheese, pulses, potatoes, fruits, desserts and sugars. The results of this study provide further indications on dietary correlates of RCC, and in particular indicate that a diet rich in refined cereals and poor in vegetables may have an unfavorable role on RCC.     

Dietary risk factors for upper aerodigestive tract cancers

We examined the association between whole-grain intake and incident upper aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer-free women. We also studied established risk factors for upper aerodigestive cancers, including fruit and vegetable intake, smoking and alcohol intake. A mailed questionnaire at baseline in 1986 included a food-frequency questionnaire and assessment of other cancer risk factors. During the 14-year follow-up period, 169 women developed cancer of the upper aerodigestive tract. For all upper aerodigestive cancers together, significant inverse associations were observed for the highest compared to the lowest tertile of whole grains [relative risk (RR) = 0.53, 95% confidence interval (CI) 0.34-0.81] and yellow/orange vegetables (RR = 0.58, 95% CI 0.39-0.87). In addition, those in the highest compared to lowest tertile of fiber intake from whole grain were less likely to develop upper aerodigestive tract cancer (RR = 0.56, 95% CI 0.37-0.84); fiber intake from refined grain was not significantly associated with upper aerodigestive tract cancer. Findings were generally similar for oropharyngeal (n = 53), laryngeal (n = 21), nasopharyngeal/salivary (n = 18), esophageal (n = 21) and gastric (n = 56) cancers, though numbers of cases were too small for statistical testing within individual cancers. These findings confirm previous observations that high intake of fruits and vegetables and that intake of whole grains and the fiber derived from them may reduce risk of upper aerodigestive tract cancers.