Cigar, pipe, and cigarette smoking and bladder cancer risk in European men

Objective: Estimating the risk of bladder cancer from cigar and pipe smoking is complicated by a small number of non-cigarette smokers included in most relevant studies. Methods: We undertook a pooled analysis of the data on men from six published case–control studies from Denmark, France, Germany, and Spain, to assess the association between pipe and cigar smoking and bladder cancer, and to compare it with the risk from cigarette smoking. Complete history of tobacco smoking was ascertained separately for cigarettes, cigars, and pipe. Odds ratios (ORs) were estimated after adjusting for age, study, and employment in high-risk occupations. Results: The pooled data set comprised 2279 cases and 5268 controls, of whom 88 cases and 253 controls smoked only cigars or pipe. The OR for pure cigarette smoking was 3.5 (95% confidence interval [CI] 2.9–4.2), that for pure pipe smoking was 1.9 (95% CI 1.2–3.1) and that for pure cigar smoking was 2.3 (95% CI 1.6–3.5). The increase in the OR of bladder cancer that was observed with duration of smoking was non-significantly lower for cigars than for cigarettes. Conclusion: Our results suggest that smoking of cigars and pipe is carcinogenic to the urinary bladder, although the potency might be lower than for cigarettes.     

Folate-related genes and the risk of tobacco-related cancers in Central Europe

Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.     

Cigar and pipe smoking and lung cancer risk: a multicenter study from Europe

BACKGROUND: Because limited information is available on the quantitative association between consumption of tobacco products other than cigarettes and lung cancer risk, we undertook a case-control study of this relationship. METHODS: We investigated lung cancer risk among smokers of cigars and/or cigarillos only and of pipes only and compared these risks with the risk of smokers of cigarettes only in a case-control study conducted in seven European areas. Our study population consisted of 5621 male case patients with lung cancer and 7255 male control subjects. Each subject or his proxy was interviewed with respect to the subject's smoking history and other risk factors for lung cancer. RESULTS: The odds ratio (OR) for smoking cigars and cigarillos only was 9.0 (95% confidence interval [CI] = 5.8-14.1), based on 43 exposed case patients and 77 exposed control subjects, and the OR for smoking a pipe only was 7.9 (95% CI = 5.3-11.8), representing 61 case patients and 129 control subjects. The OR for smoking cigarettes only was 14.9 (95% CI = 12.3-18.1), based on 4204 case patients and 3930 control subjects. A dose-response relationship was present for duration of use and cumulative consumption both for cigars and cigarillos and for pipe tobacco. An effect was also suggested for inhalation of cigar and cigarillo smoke. The dose-response relationships between lung cancer risk and either duration of smoking or average and cumulative consumption were similar for cigar and cigarillo smoking, pipe smoking, and cigarette smoking. CONCLUSION: Our results suggest that smoking of European cigars, cigarillos, and pipe tobacco might exert a carcinogenic effect on the lung comparable to that of cigarettes.     

Gene-environment interaction in tobacco-related cancers

This review summarizes the carcinogenic effects of tobacco smoke and the basis for interaction between tobacco smoke and genetic factors. Examples of published papers on gene-tobacco interaction and cancer risk are presented. The assessment of gene-environment interaction in tobacco-related cancers has been more complex than originally expected for several reasons, including the multiplicity of genes involved in tobacco metabolism, the numerous substrates metabolized by the relevant genes and the interaction of smoking with other metabolic pathways. Future studies on gene-environment interaction and cancer risk should include biomarkers of smoking dose, along with markers of quantitative historical exposure to tobacco. Epigenetic studies should be added to classic genetic analyses, in order to better understand gene-environmental interaction and individual susceptibility. Other metabolic pathways in competition with tobacco genetic metabolism/repair should be incorporated in epidemiological studies to generate a more complete picture of individual cancer risk associated with environmental exposure to carcinogens.     

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.     

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.     

Cigarette smoking and risk of prostate cancer in middle-aged men.

Cigarette smoking may increase the risk of prostate cancer by affecting circulating hormone levels or through exposure to carcinogens. Although there are plausible mechanisms that could explain an association between smoking and prostate cancer, previous studies are inconsistent. The goal of this population-based case-control study was to assess this association in middle-aged men. Cases (n = 753) were men ages 40-64 years diagnosed with prostate cancer from 1993 to 1996 identified using the Seattle-Puget Sound Cancer Registry. Age-matched controls without prostate cancer from the same region (n = 703) were identified using random digit dialing. Participants completed detailed in-person interviews. Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess the prostate cancer-cigarette smoking relationship. Current smokers had an increased risk (OR = 1.4, 95% CI 1.0-2.0) relative to nonsmokers. A dose-response relationship was noted between number of pack-years smoked and prostate cancer risk (trend P = 0.03). The OR = 1.6 (95% CI 1.1-2.2) for men with >40 pack-years of smoking, with a stronger association observed in men with more aggressive disease (OR = 2.0, 95% CI 1.3-3.1). Smoking cessation resulted in a decline in risk (trend P = 0.02). Smoking is associated with a moderately increased relative risk of prostate cancer. Furthermore, a dose-response relationship exists between number of pack-years smoked and cancer risk. Given that smoking cessation seems to reduce these risks, results from this study have public health ramifications and suggest that prostate cancer should be added to the list of tumors for which cigarette smoking is a risk factor.     

Cancer incidence correlations: genital, urinary and some tobacco-related cancers

Bivariate correlations between sex-specific age-adjusted incidence rates of 10 genital and urinary tract cancer sites and lung cancer were calculated. The data base used was that published in the 5th edition of the series Cancer incidence in five continents. The purpose of the analyses was to test the consistency of the data with the hypothesis of a common risk factor for genital cancers and other cancers of the urinary tract and for lung and genital cancers. The results indicate that the incidence of cervical cancer is strongly correlated with that of cancer of the penis, of other cancers of the female genital tract and of chorioepithelioma. In countries at low/intermediate risk for cervical cancer (mostly developed Western countries), the incidence of cervical cancer is also correlated with that of lung cancer in males. The incidence of male lung cancer is, moreover, strongly correlated with cancers of the prostate, penis, testis, bladder and other urinary tract cancers. These analyses support the views that: urogenital cancers in both sexes might share (a) common risk factor(s), which may be certain types of human papilloma-virus; and that cigarette smoking is likely to be a risk factor for most of these cancers in countries where the use of tobacco has been widespread for a long time. Other suggestive etiological conclusions about less well-studied cancer sites are also presented.     

Cigar and pipe smoking and cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

The carcinogenicity of cigar and pipe smoking is established but the effect of detailed smoking characteristics is less well defined. We examined the effects on cancer incidence of exclusive cigar and pipe smoking, and in combination with cigarettes, among 102,395 men from Denmark, Germany, Spain, Sweden and the United Kingdom in the EPIC cohort. Hazard ratios (HR) and their 95% confidence intervals (CI) for cancer during a median 9‐year follow‐up from ages 35 to 70 years were estimated using proportional hazards models. Compared to never smokers, HR of cancers of lung, upper aerodigestive tract and bladder combined was 2.2 (95% CI: 1.3, 3.8) for exclusive cigar smokers (16 cases), 3.0 (2.1, 4.5) for exclusive pipe smokers (33 cases) and 5.3 (4.4, 6.4) for exclusive cigarette smokers (1,069 cases). For each smoking type, effects were stronger in current smokers than in ex‐smokers and in inhalers than in non‐inhalers. Ever smokers of both cigarettes and cigars [HR 5.7 (4.4, 7.3), 120 cases] and cigarettes and pipes [5.1 (4.1, 6.4), 247 cases] had as high a raised risk as had exclusive cigarette smokers. In these smokers, the magnitude of the raised risk was smaller if they had switched to cigars or pipes only (i.e., quit cigarettes) and had not compensated with greater smoking intensity. Cigar and pipe smoking is not a safe alternative to cigarette smoking. The lower cancer risk of cigar and pipe smokers as compared to cigarette smokers is explained by lesser degree of inhalation and lower smoking intensity.     

Estimation of relative risk from vital data: smoking and cancers of the lung and bladder.

Mortality data from cancers of the lung and bladder in England and Wales were analyzed. With the use of detailed information on cigarette consumption, a nonlinear least-squares analysis showed that the differences between males and females in the rates of these cancers could be explained on the basis of differences in smoking habits. Furthermore, estimates of the relative risk due to smoking were obtained. The relative risks of smoking 146,000 cigarettes (equivalent to 20 cigarettes/day for 20 yr) were 4.3 for lung cancer and 2.9 for bladder cancer. These estimates agree with those obtained by other types of epidemiologic studies.     

Number of children and death from hormone-dependent cancers

The association between number of children of current marriage reported by 431,604 women aged 45-74 years at the Norwegian Census in 1970 and mortality, at follow-up through 1985, from hormone-dependent cancers, i.e., cancers of breast, corpus uteri and ovary combined, has been investigated. The reduction in age-adjusted mortality was 9.6% (95% confidence interval; 8.3-10.9%) for each child with no deviation from linearity. Women with 8-11 children had a relative risk of 0.34 (0.25-0.47) compared to nullipara. Adjustment for age at first birth slightly changed the effect of number of children on mortality to 9.3% per child. The reduction in mortality per child was for cancer of the breast 7.2%, corpus uteri 12.2% and ovary 12.7%. Our findings indicate that having few children is a major risk factor for death from the 3 hormone-dependent cancers combined.     

Independent and combined effects of tobacco smoking,chewing and alcohol drinking on the risk of oral,pharyngeal and esophageal cancers in Indian men

Oral, pharyngeal and esophageal cancers are 3 of the 5 most common cancer sites in Indian men. To assess the effect of different patterns of smoking, chewing and alcohol drinking in the development of the above 3 neoplasms and to determine the interaction among these habits, we conducted a case-control study in Chennai and Trivandrum, South India. The cases included 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients who were compared with 1,711 male disease controls from the 2 centers as well as 1,927 male healthy hospital visitors from Chennai. We observed a significant dose-response relationship for duration and amount of consumption of the 3 habits with the development of the 3 neoplasms. Tobacco chewing emerged as the strongest risk factor for oral cancer, with the highest odds ratio (OR) for chewing products containing tobacco of 5.05 [95% confidence internal (CI) 4.26-5.97]. The strongest risk factor for pharyngeal and esophageal cancers was tobacco smoking, with ORs of 4.00 (95% CI 3.07-5.22) and 2.83 (95% CI 2.18-3.66) in current smokers, respectively. An independent increase in risk was observed for each habit in the absence of the other 2. For example, the OR of oral cancers for alcohol drinking in never smokers and never chewers was 2.56 (95% CI 1.42-4.64) and that of esophageal cancers was 3.41 (95% CI 1.46-7.99). Furthermore, significant decreases in risks for all 3 cancer sites were observed in subjects who quit smoking even among those who had quit smoking 2-4 years before the interview.     

Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers

We reported previously that subjects homozygous for the cytochrome P450 2A6 (CYP2A6) (*)4 have a lower risk of lung cancer. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for lung cancer could be found in subjects possessing novel CYP2A6 variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored CYP2A6(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for lung cancer were significantly lower in subjects who harbored CYP2A6(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the CYP2A6 genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), lung cancer risk was found to be less in subjects with the variant of CYP2A6 alleles [group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)]. The reduced risk for lung cancer was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and small cell carcinoma (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the CYP2A6 is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer.