Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium.
ABSTRACT: BACKGROUND:The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. METHODS:The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis. RESULTS:Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. CONCLUSIONS:In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. IMPACT:Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
Project description: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.
Project description:The association between leisure-time physical activity (LTPA) and male breast cancer risk is unclear. In the Male Breast Cancer Pooling Project, with 449 cases and 13,855 matched controls, we used logistic regression with study stratification to generate adjusted ORs and 95% confidence intervals (CI) for LTPA tertiles and male breast cancer risk. Compared with low LTPA, medium and high LTPA were not associated with male breast cancer risk (OR, 1.01; 95% CI, 0.79-1.29; 0.90, 0.69-1.18, respectively). In joint-effects analyses, compared with the referent of high body mass index (BMI; ?25 kg/m(2))/low LTPA, neither medium nor high PA was associated with risk among high BMI men, but normal BMI men (<25 kg/m(2)) with low or medium LTPA were at a nonsignificant ?16% reduced risk and those with high LTPA were at a 27% reduced risk (OR, 0.73; 95% CI, 0.50-1.07). Physical activity alone may not confer protection against male breast cancer risk.
Project description:BACKGROUND:Although long-term alcohol and tobacco use have widely been recognised as important risk factors for cancer, the impacts of alcohol and tobacco health policies on cancer mortality have not been examined in previous studies. This study aims to estimate the association of key alcohol and tobacco policy or events in Australia with changes in overall and five specific types of cancer mortality between the 1950s and 2013. METHODS:Annual population-based time-series data between 1911 and 2013 on per capita alcohol and tobacco consumption and head and neck (lip, oral cavity, pharynx, larynx and oesophagus), lung, breast, colorectum and anus, liver and total cancer mortality data from the 1950s to 2013 were collected from the Australian Bureau of Statistics and Cancer Council Victoria, the WHO Cancer Mortality Database and the Australian Institute of Health and Welfare. The policies with significant relations to changes in alcohol and tobacco consumption were identified in an initial model. Intervention dummies with estimated lags were then developed based on these key alcohol and tobacco policies and events and inserted into time-series models to estimate the relation of the particular policy changes with cancer mortality. RESULTS:Liquor licence liberalisation in the 1960s was significantly associated with increases in the level of population drinking and thereafter of male cancer mortality. The introduction of random breath testing programs in Australia after 1976 was associated with a reduction in population drinking and thereafter in cancer mortality for both men and women. Meanwhile, the release of UK and US public health reports on tobacco in 1962 and 1964 and the ban on cigarette ads on TV and radio in 1976 were found to have been associated with a reduction in Australian tobacco consumption and thereafter a reduction in mortality from all cancer types except liver cancer. Policy changes on alcohol and tobacco during the 1960s-1980s were associated with greater changes for men than for women, particularly for head and neck, lung and colorectum cancer sites. CONCLUSION:This study provides evidence that some changes to public health policies in Australia in the twentieth century were related to the changes in the population consumption of alcohol and tobacco, and in subsequent mortality from various cancers over the following 20?years.
Project description:Little is known about socioeconomic inequalities in male cancer incidence in nonwestern settings. Using the nationwide clinical and occupational inpatient data (1984-2016) in Japan, we performed a multicentered, matched case-control study with 214 123 male cancer cases and 1 026 247 inpatient controls. Based on the standardized national classifications, we grouped patients' longest-held occupational class (blue-collar, service, professional, manager), cross-classified by industrial cluster (blue-collar, service, white-collar). Using blue-collar workers in blue-collar industries as the referent group, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression with multiple imputation, matched for age, admission date, and admitting hospital. Smoking and alcohol consumption were additionally adjusted. Across all industries, a reduced risk with higher occupational class (professionals and managers) was observed for stomach and lung cancer. Even after controlling for smoking and alcohol consumption, the reduced odds persisted: OR of managers in white-collar industries was 0.80 (95% CI 0.72-0.90) for stomach cancer, and OR of managers in white-collar industries was 0.66 (95% CI 0.55-0.79) for lung cancer. In white-collar industries, higher occupational class men tended to have lower a reduced risk for most common types of cancer, with the exception of professionals who showed an excess risk for prostate cancer. We documented socioeconomic inequalities in male cancer incidence in Japan, which could not be explained by smoking and alcohol consumption.
Project description:BACKGROUND:Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood. METHODS:We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis. RESULTS:Alcohol use was positively associated with PD (P trend = 0.01), unassociated with DA (P trend = 0.23), and inversely associated with NDA (P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (P trend = 0.0008), unassociated with DA (P trend = 0.93), and positively associated with NDA (P trend<0.0001). These trends were stronger in normal and overweight women than in obese women. CONCLUSIONS:These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA. IMPACT:PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health.
Project description:BACKGROUND:Fetal alcohol spectrum disorder (FASD) is associated with long-term deficits in cognitive and motor functions. Previous studies linked neurodevelopmental abnormalities to increased oxidative stress and white matter hypotrophy. However, similar effects occur with low-dose nitrosamine exposures, alcohol abuse correlates with cigarette smoking, and tobacco smoke contains tobacco-specific nitrosamines, including NNK. HYPOTHESIS:Tobacco smoke exposure is a co-factor in FASD. DESIGN:Long Evans rat pups were i.p. administered ethanol (2 g/kg) on postnatal days (P) 2, 4, 6 and/or NNK (2 mg/kg) on P3, P5, and P7 to simulate third trimester human exposures. Oligodendroglial myelin-associated, neuroglial, and relevant transcription factor mRNA transcripts were measured using targeted PCR arrays. RESULTS:Ethanol and NNK differentially altered the expression of immature and mature oligodendroglial, neuronal and astrocytic structural and plasticity-associated, and various transcription factor genes. NNK's effects were broader and more pronounced than ethanol's, and additive or synergistic effects of dual exposures impacted expression of all four categories of genes investigated. CONCLUSION:Developmental exposures to alcohol and NNK (via tobacco smoke) contribute to sustained abnormalities in brain white matter structure and function via distinct but overlapping alterations in the expression of genes that regulate oligodendrocyte survival, maturation and function, neuroglial structural integrity, and synaptic plasticity. The results support the hypothesis that smoking may contribute to brain abnormalities associated with FASD.
Project description:We aimed to examine the effect of alcohol consumption on lung cancer risk stratified by smoking, and to explore whether the impact of alcohol was modified by familial susceptibility to cancer. We recruited 1208 male lung cancer incident cases and 1069 community referents during 2004-2006 and collected their lifetime history of alcohol consumption, cigarette smoking, and family cancer history. Unconditional multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (OR). We tested multiplicative-scale interaction between exposures of interest and examined the additive-scale interaction using synergy index. A moderate association between frequent alcohol consumption and lung cancer was observed among men who had family cancer history (OR = 4.22, 95%CI: 2.46-7.23) after adjustment of smoking and other confounders, while the alcohol effect among men without family history was weak (OR = 1.24, 95%CI: 0.95-1.63) and it became no excess in the never smokers. We observed a consistent synergistic effect between alcohol drinking and family cancer history for all lung cancers and the adenocarcinoma, while there was no multiplicative-scale interaction between the exposures of interest (likelihood ratio test for interaction, p>0.05). Our study revealed a possible synergistic effect between alcohol consumption and familial susceptibility for lung cancer risk; however, this observed possible association needs to be confirmed by future larger analytic studies with more never smoking cases.
Project description:The overall objective of the study is to estimate the percentage of cancers (excluding non-melanoma skin cancer) in the UK in 2010 that were the result of exposure to 14 major lifestyle, dietary and environmental risk factors: tobacco, alcohol, four elements of diet (consumption of meat, fruit and vegetables, fibre and salt), overweight, lack of physical exercise, occupation, infections, radiation (ionising and solar), use of hormones and reproductive history (breast feeding). The number of new cases attributable to suboptimal exposure levels in the past, relative to a theoretical optimum exposure distribution, is evaluated. For most of the exposures, the attributable fraction was calculated based on the distribution of exposure prevalence (around 2000), the difference from the theoretical optimum (by age group and sex) and the relative risk per unit difference. For tobacco smoking, the method developed by Peto et al (1992) was used, which relies on the ratio between observed incidence of lung cancer in smokers and that in non-smokers, to calibrate the risk. This article outlines the structure of the supplement - a section for each of the 14 exposures, followed by a Summary chapter, which considers the relative contributions of each factor to the total number of cancers diagnosed in the UK in 2010 that were, in theory, avoidable.
Project description:This chapter summarises the results of the preceding sections, which estimate the fraction of cancers occurring in the UK in 2010 that can be attributed to sub-optimal, past exposures of 14 lifestyle and environmental risk factors. For each of 18 cancer types, we present the percentage of cases attributable to one or all of the risk factors considered (tobacco, alcohol, four elements of diet (consumption of meat, fruit and vegetables, fibre, and salt), overweight, lack of physical exercise, occupation, infections, radiation (ionising and solar), use of hormones, and reproductive history (breast feeding)).Exposure to less than optimum levels of the 14 factors was responsible for 42.7% of cancers in the UK in 2010 (45.3% in men, 40.1% in women)--a total of about 134,000 cases.Tobacco smoking is by far the most important risk factor for cancer in the UK, responsible for 60, 000 cases (19.4% of all new cancer cases) in 2010. The relative importance of other exposures differs by sex. In men, deficient intake of fruits and vegetables (6.1%), occupational exposures (4.9%) and alcohol consumption (4.6%) are next in importance, while in women, it is overweight and obesity (because of the effect on breast cancer)--responsible for 6.9% of cancers, followed by infectious agents (3.7%).Population-attributable fractions provide a valuable quantitative appraisal of the impact of different factors in cancer causation, and are thus helpful in prioritising cancer control strategies. However, quantifying the likely impact of preventive interventions requires rather complex scenario modelling, including specification of realistically achievable population distributions of risk factors, and the timescale of change, as well as the latent periods between exposure and outcome, and the rate of change following modification in exposure level.
Project description:BACKGROUND:Incidence of small-intestine neuroendocrine tumors (SINT) has been increasing in the United States over the past 40 years, with higher incidence in Utah than elsewhere. As information about how these tumors arise is limited, elucidating lifestyle factors associated with SINT in a statewide cohort could potentially identify those at risk to help mitigate their effects. METHODS:Cases of SINT with a carcinoid histology (8240 or 8241) diagnosed in Utah from 1996 to 2014 with no prior history of cancer within 5 years (n = 433) were matched to population controls (1:10 ratio). Tobacco and alcohol exposures before case diagnosis were identified from International Classification of Diseases codes in statewide medical records and from self-reported data captured at patient encounters beginning in 1996. Multivariate logistic regression was used to estimate risk of SINT associated with tobacco and alcohol in cases compared with controls. RESULTS:An increased risk of SINT was observed in tobacco-exposed individuals compared with unexposed [OR, 1.44; 95% confidence interval (CI), 1.11-1.86; P = 0.006]. Those who were exposed to alcohol exhibited an increased risk of SINT (OR, 1.62; 95% CI, 1.05-2.49; P = 0.03). CONCLUSIONS:This study supports tobacco and alcohol use as risk factors for SINT, independent of family history. However, low rates of smoking and alcohol use in Utah coupled with higher rates of SINT suggest other factors may contribute to development of these tumors. IMPACT:Although tobacco and alcohol modestly contribute to risk, our study suggests in addition to greater detection of tumors, other as-of-yet undefined exposures may drive rising SINT incidence.