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Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Background: Cigarette smoking is among the few unequivocal risk factors for the development of pancreatic ductal adenocarcinoma (PDAC). Activating mutations in codon 12 of the K-ras protooncogene is a frequent and early molecular event in the pathogenesis of PDAC and a variety of nonmalignant ductal pancreatic lesions. The molecular epidemiologic relation between heavy cigarette smoking and mutational activation of K-ras in PDAC has been examined to a limited extent. The authors have examined the mutational status of K-ras in nonneoplastic pancreata in relation to cigarette smoking status., Methods: Archival formalin fixed paraffin embedded specimens of nonneoplastic pancreata (n = 39) were obtained from the American Cancer Society and evaluated histopathologically. Specimens from age- and gender-matched individuals were stratified into three groups: 1) those who never smoked cigarettes (n = 16), 2) those who smoked 1-2 packs/day for more than 20 years (n = 10 cases), and 3) those who smoked more than 2 packs/day for 20 or more years (n = 13). Cases were preselected from 77 specimens based on the quality, suitability, and cellularity of the archival tissues for analyses. Furthermore, none of the patients died of primary PDAC or had evidence of pancreatic metastases from an extrapancreatic primary tumor. Tissue sections were microdissected and deparaffinized, and genomic DNA was purified by standard proteinase K-phenol-chloroform extraction techniques. Genomic DNA was analyzed for mutations in codon 12 of the K-ras protooncogene by two mutant-allele-enriched polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assays and by multiplex PCR-based ligase chain reaction (LCR) analyses., Results: Analyses of multiple microdissected pancreata specimens from 39 cases revealed wild-type K-ras codon 12 sequences in both nonsmoking individuals and those who smoked 1-2 packs/day for 20 or more years. K-ras codon 12 mutations were confirmed by PCR-RFLP and PCR-LCR assays in 5 of 13 pancreata cases (39%) obtained from individuals who smoked more than 2 packs of cigarettes/day for 20 years or more (P < 0.005). The K-ras mutation spectra revealed two G-->T transversions, one G-->C transversion and two G-->A transitions. There was no clear relation between the incidence or spectra of mutations and pancreatic histopathology, as overtly normal pancreata as well as pancreata with squamous metaplasia, periductal fibrosis, and ductal atypia revealed reproducible K-ras alterations. Similarly, among those 34 cases in which a wild-type K-ras sequence was revealed by both approaches, a similar histopathologic profile was evident., Conclusions: Mutational activation of codon 12 of the K-ras protooncogene was confirmed reproducibly by mutant allele-enriched PCR-RFLP and multiplex PCR-LCR analyses in 39% (5 of 13) of archival nonneoplastic pancreata from age- and gender-matched individuals who smoked more than 2 packs of cigarettes/day for 20 or more years. The presence of a mutated or wild-type or K-ras was independent of the histopathologic profile of the 39 cases examined. The data provide further suggestive molecular epidemiologic evidence of an association between a major and unequivocal risk factor for PDAC (heavy cigarette smoking) and mutations in a molecular target (K-ras), the activation of which is an important and early event both in the pathogenesis of PDAC and in the development of a variety of nonneoplastic ductal pancreatic lesions.

Background: Adenocarcinoma of the lung, once considered minimally related to cigarette smoking, has become the most common type of lung cancer in the United States. The increased incidence of this cancer might be explained by advances in diagnostic technology (i.e., increased ability to perform biopsies on tumors in smaller, more distal airways), changes in cigarette design (e.g., the adoption of filtertips), or changes in smoking practices. We examined data from the Connecticut Tumor Registry and two American Cancer Society studies to explore these possibilities., Methods: Connecticut Tumor Registry data from 1959 through 1991 were analyzed to determine whether the increase in lung adenocarcinoma observed during that period could be best described by birth cohort effects (i.e., generational changes in cigarette smoking) or calendar period effects (i.e., diagnostic advances). Associations between cigarette smoking and death from specific types of lung cancer during the first 2 years of follow-up in Cancer Prevention Study I (CPS-I), initiated in 1959) and Cancer Prevention Study II (CPS-II, initiated in 1982) were also examined., Results: Adenocarcinoma incidence in Connecticut increased nearly 17-fold in women and nearly 10-fold in men from 1959 through 1991. The increases followed a clear birth cohort pattern, paralleling gender and generational changes in smoking more than diagnostic advances. Cigarette smoking became more strongly associated with death from lung adenocarcinoma in CPS-II compared with CPS-I, with relative risks of 19.0 (95% confidence interval [CI] = 8.3-47.7) for men and 8.1 (95% CI = 4.5-14.6) for women in CPS-II and 4.6 (95% CI = 1.7-12.6) for men and 1.5 (0.3-7.7) for women in CPS-I., Conclusions: The increase in lung adenocarcinoma since the 1950s is more consistent with changes in smoking behavior and cigarette design than with diagnostic advances.

The authors examined the relation between smoking and the risk of fatal prostate cancer in a large prospective mortality study of 450,279 men who were cancer free at enrollment in 1982. During 9 years of follow-up, 1,748 deaths occurred from prostate cancer. Cox proportional hazards modeling was used to adjust for other risk factors. Current cigarette smoking was associated with fatal prostate cancer (rate ratio = 1.34, 95% confidence interval (CI) 1.16-1.56). The rate ratio was greater at younger ages, decreasing from 1.83 (95% CI 1.04-3.24) among men below the age of 60 years to 1.11 (95% CI 0.79-1.58) among men aged 80 years and above (p for trend = 0.16). No trend in risk was observed with the number of cigarettes per day or with the duration of smoking among current smokers at baseline, and no increased risk was found among former smokers. Race did not significantly modify the association between cigarette smoking and fatal prostate cancer. These data, together with those of three other large prospective studies that find higher death rates from prostate cancer in current cigarette smokers, and inconsistent findings in incidence studies suggest that smoking may adversely affect survival in prostate cancer patients.

Objectives: This study was undertaken to examine changes in smoking-specific death rates from the 1960s to the 1980s., Methods: In two prospective studies, one from 1959 to 1965 and the other from 1982 to 1988, death rates from lung cancer, coronary heart disease, and other major smoking-related diseases were measured among more than 200,000 current smokers and 480,000 lifelong non-smokers in each study., Results: From the first to the second study, lung cancer death rates (per 100,000) among current cigarette smokers increased from 26 to 155 in women and from 187 to 341 in men; the increase persisted after current daily cigarette consumption and years of smoking were controlled for. Rates among nonsmokers were stable. In contrast, coronary heart disease and stroke death rates decreased by more than 50% in both smokers and nonsmokers. The all-cause rate difference between smokers and nonsmokers doubled for women but was stable for men., Conclusions: Premature mortality (the difference in all-cause death rates between smokers and nonsmokers) doubled in women and continued unabated in men from the 1960s to the 1980s. Lung cancer surpassed coronary heart disease as the largest single contributor to smoking-attributable death among White middle-class smokers.

The authors examined the association of fatal breast cancer and cigarette smoking in a large, prospective mortality study of US adults. After 6 years of follow-up, 880 cases of fatal breast cancer were observed in a cohort of 604,412 women who were cancer-free at interview in 1982. Cox proportional hazards modeling, adjusted for other risk factors, found that current smoking was significantly related to fatal breast cancer risk (adjusted rate ratio (RR) = 1.26, 95% confidence interval (CI) 1.05-1.50). A negative association was observed for former smokers, but this was not statistically significant (RR = 0.85, 95% CI 0.70-1.03). The association of current smoking with fatal breast cancer risk increased with increasing numbers of cigarettes per day and with total number of years smoked. For smokers of 40 or more cigarettes per day, the rate ratio was 1.74 (95% CI 1.15-2.62). The authors hypothesize that these results may be due to either a poorer prognosis among breast cancer cases who smoke or a delayed diagnosis among current smokers who do not receive mammograms as often as never or former smokers. Women who smoke should be targeted for breast cancer screening services.