Alcohol Consumption, Cigarette Smoking, and Familial Breast Cancer Risk

Findings From the Prospective Family Study Cohort (ProF-SC)

Nur Zeinomar; Julia A. Knight; Jeanine M. Genkinger; Kelly-Anne Phillips; Mary B. Daly; Roger L. Milne; Gillian S. Dite; Rebecca D. Kehm; Yuyan Liao; Melissa C. Southey; Wendy K. Chung; Graham G. Giles; Sue-Anne McLachlan; Michael L. Friedlander; Prue C. Weideman; Gord Glendon; Stephanie Nesci; kConFab Investigators; Irene L. Andrulis; Saundra S. Buys; Esther M. John; Robert J. MacInnis; John L. Hopper; Mary Beth Terry


Breast Cancer Res. 2019;21(128) 

In This Article


We did not observe a statistically significant increase in BC risk associated with alcohol or tobacco consumption when considering the cohort as a whole, but we did observe some differences by FRP and ER status. Specifically, alcohol intake was associated with increased risk of ER-positive BC for women at lower predicted absolute risk. For women with a high FRP (above 95th percentile or a 5-year BOADICEA of 6.55%) who also consumed alcohol, smoking was associated with increased overall BC risk.

Five previous studies have reported increased BC risk associated with smoking only for women with a family history of BC or in BRCA1 and BRCA2 mutation carriers.[32–36] This includes a report from the UK Generations study cohort of a 35% increased BC risk (HR 1.35; 95 CI 1.12–1.62) for women with a family history of BC who ever smoked, and no increased risk for smokers with no family history of BC.[32] Similarly, the Minnesota breast cancer family study reported ever smoking was associated with a 2.4-fold increased risk for daughters or sisters of women with BC, but not for their nieces or granddaughters.[34] A secondary analysis of high-risk women enrolled in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial reported that smoking has a greater influence on BC risk for women with an elevated risk of BC.[35] Additionally, we previously reported an association between smoking and increased BC risk for BRCA1 and BRCA2 mutation carriers aged less than 50 years.[36] In the current study, we found a positive interaction between smoking and FRP only for regular alcohol drinkers, pointing to a possible synergistic relationship between FRP, smoking, and alcohol with respect to BC risk. This is consistent with three previous studies, including a reanalysis of over 22,000 BC cases and a pooled analysis of 14 cohort studies that examined the smoking association by alcohol consumption and found significant associations with measures of smoking only for alcohol drinkers.[8,19,32]

We observed evidence for a negative interaction between FRP and alcohol intake in association with ER-positive disease. As previously reported, our family-based cohort is comprised of women across a large range of familial risk.[12] In addition to being enriched with women at higher than average risk, over 30% of cohort participants are at general population risk (5-year BOADICEA < 1.67%), similar to other cohorts unselected for underlying risk. As such, our finding of an increased risk for higher alcohol intake in women at the lower end of the FPR spectrum, which translates into a 5-year BOADICEA < 1.25%, is consistent with previous reports from average-risk populations of a stronger association between alcohol intake and risk of hormone receptor positive tumors.[5]

We were limited to active smoking exposure and did not have information on exposure to environmental tobacco smoke (ETS). Some studies have reported an association with ETS and elevated BC risk, as reviewed elsewhere.[37] Another limitation is that information on smoking and alcohol came from self-report of recalled information, which may not be accurate, particularly with respect to amount, frequency, and duration of alcohol intake. However, because the present study was prospective, any measurement error would be non-differential. We also did not have information on binge drinking and could not assess this association with BC risk. Additionally, the prevalence of reported alcohol consumption in our population was low, so we had limited power to fully assess interaction with FRP at different levels of alcohol consumption, particularly for heavier drinkers and by BC subtype. Similarly, for cigarette smoking, our study was limited by a small number of cases who smoked to fully assess interaction with FRP, particularly by BC subtype.

Our study is strengthened by the comprehensive definition of family history that incorporates pedigree information and age at diagnosis of the relatives, extending beyond the conventional binary variable to cover the entire familial risk profile. The heterogeneity of the cohort with respect to family history allowed us to evaluate women across the full spectrum of risk and, in particular, women at high familial risk.