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Alcohol consumption, cigarette smoking, and familial breast cancer risk: findings from the Prospective Family Study Cohort (ProF-SC).

ABSTRACT: BACKGROUND:Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman's familial BC risk. METHODS:Using the Prospective Family Study Cohort, we evaluated associations between alcohol consumption, cigarette smoking, and BC risk. We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (CI). We examined whether associations were modified by familial risk profile (FRP), defined as the 1-year incidence of BC predicted by Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a pedigree-based algorithm. RESULTS:We observed 1009 incident BC cases in 17,435 women during a median follow-up of 10.4?years. We found no overall association of smoking or alcohol consumption with BC risk (current smokers compared with never smokers HR 1.02, 95% CI 0.85-1.23; consuming ??7 drinks/week compared with non-regular drinkers HR 1.10, 95% CI 0.92-1.32), but we did observe differences in associations based on FRP and by estrogen receptor (ER) status. Women with lower FRP had an increased risk of ER-positive BC associated with consuming ??7 drinks/week (compared to non-regular drinkers), whereas there was no association for women with higher FRP. For example, women at the 10th percentile of FRP (5-year BOADICEA?=?0.15%) had an estimated HR of 1.46 (95% CI 1.07-1.99), whereas there was no association for women at the 90th percentile (5-year BOADICEA?=?4.2%) (HR 1.07, 95% CI 0.80-1.44). While the associations with smoking were not modified by FRP, we observed a positive multiplicative interaction by FRP (pinteraction?=?0.01) for smoking status in women who also consumed alcohol, but not in women who were non-regular drinkers. CONCLUSIONS:Moderate alcohol intake was associated with increased BC risk, particularly for women with ER-positive BC, but only for those at lower predicted familial BC risk (5-year BOADICEA

SUBMITTER: Zeinomar N

PROVIDER: S-EPMC6883541 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Alcohol consumption, cigarette smoking, and familial breast cancer risk: findings from the Prospective Family Study Cohort (ProF-SC).

Zeinomar Nur N Knight Julia A JA Genkinger Jeanine M JM Phillips Kelly-Anne KA Daly Mary B MB Milne Roger L RL Dite Gillian S GS Kehm Rebecca D RD Liao Yuyan Y Southey Melissa C MC Chung Wendy K WK Giles Graham G GG McLachlan Sue-Anne SA Friedlander Michael L ML Weideman Prue C PC Glendon Gord G Nesci Stephanie S Andrulis Irene L IL Buys Saundra S SS John Esther M EM MacInnis Robert J RJ Hopper John L JL Terry Mary Beth MB

Breast cancer research : BCR 20191128 1

<h4>Background</h4>Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman's familial BC risk.<h4>Methods</h4>Using the Prospective Family Study Cohort, we evaluated associations between alcohol consumption, cigarette smoking, and BC risk. We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (CI). We examined whether associations ...[more]

PMID: 31779655

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Project description:BackgroundClozapine is an effective antipsychotic medication for patients with treatment-resistant schizophrenia. Previous studies revealed that smoking, alcohol intake, and coffee consumption altered the metabolism of clozapine. However, causal associations between substance use and clozapine levels were not sufficiently established.MethodsSeveral genome-wide association studies provided genetic tools for six measures of substance use, including age of smoking, cigarettes per day, smoking cessation, smoking initiation, coffee consumption, and alcohol consumption (GWASs). Utilizing the CLOZUK consortium's dataset, their associations with clozapine and its metabolite concentrations were evaluated. All GWAS data were collected from the European population. Mendelian randomization (MR) estimations from each genetic test were combined using inverse variance weighted (IVW) meta-analysis in combination with complementing techniques (such as weighted median and MR Egger). We also analyze horizontal pleiotropy and heterogeneity using various sensitivity analyses.ResultsGenetically predicted higher level of smoking initiation was significantly associated with reduced clozapine (β = -0.14, P = 4.53E-04) concentrations and norclozapine concentrations (β = -0.14, P = 3.33E-04), and increased coffee consumption was significantly associated with lower level of clozapine concentrations (β = -0.42, P = 1.70E-14), norclozapine concentrations (β = -0.27, P = 1.51E-07), and the metabolic ratio of clozapine to norclozapine (β = -0.15, P = 5.35E-07), survived after the Bonferroni correction (P = 0.05/6 = 0.008). In sensitivity analyses, the weighted median and MR Egger methods demonstrated directionally consistent effects. In addition, our sensitive test indicated no significant horizontal pleiotropy and heterogeneity (P > 0.05). However, other measures of substance use (age of initiation smoking, cigarettes per day, smoking cessation, and drinks per week) were not associated with clozapine metabolism.ConclusionOur investigation revealed a correlation between greater smoking initiation and coffee consumption and reduced blood levels of clozapine and norclozapine. Providing clinicians with guidance on how to adjust clozapine levels for clozapine-treated patients.

Project description:[Correction Notice: An Erratum for this article was reported in Vol 103(1) of Journal of Applied Psychology (see record 2017-44578-001). In the article, the authors incorrectly used the term "probability" instead of the term "odds" when relating to the impact of drinking in college on post-graduation employment. The abstract should note "a roughly 10% reduction in the odds...", and in the 2nd paragraph of the Discussion section, (a) "a roughly 10% lower probability" should be "a roughly 10% lower odds", and (b) "their probability of full-time employment upon graduation is roughly 6% lower than..." should be "their odds of full-time employment upon graduation is roughly 6% lower than..." All versions of this article have been corrected.] Although scholars have extensively studied the impact of academic and vocational factors on college students' employment upon graduation, we still know little as to how students' health-related behaviors influence such outcomes. Focusing on student alcohol use as a widely prevalent, health-related behavior, in the current study, we examined the employment implications of student drinking behavior. Drawing from literature examining the productivity effects of drinking and research on job search, we posited that modal quantity and frequency of alcohol consumption, as well as the frequency of heavy episodic drinking (HED) adversely impact the probability of employment upon graduation. Using data from 827 graduating seniors from 4 geographically diverse universities in the United States collected in the context of a prospective study design, we found modal alcohol consumption to have no adverse effect on the likelihood of employment upon graduation. However, we did find a significant adverse effect for the frequency of heavy drinking, with the data suggesting a roughly 10% reduction in the odds of employment upon graduation among college seniors who reported engaging in the average level of HED. The theoretical and practical implications of these findings are discussed. (PsycINFO Database Record

Dataset Information

Alcohol consumption, cigarette smoking, and familial breast cancer risk: findings from the Prospective Family Study Cohort (ProF-SC).

Publications

Alcohol consumption, cigarette smoking, and familial breast cancer risk: findings from the Prospective Family Study Cohort (ProF-SC).

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