Dataset Information

Alcohol Consumption, Cigarette Smoking, and Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Results from The BRCA1 and BRCA2 Cohort Consortium.

ABSTRACT:

Background

Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer, but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high breast cancer risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with breast cancer risk is essential.

Methods

Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers and 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers and 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models.

Results

For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with breast cancer risk, except smoking for more than 5 years before a first full-term pregnancy (FFTP) when compared with parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HR_R) was 1.19 [95% confidence interval (CI), 1.02-1.39] and the HR from prospective analysis (HR_P) was 1.36 (95% CI, 0.99-1.87). For BRCA2 mutation carriers, smoking for more than 5 years before an FFTP showed an association of a similar magnitude, but the confidence limits were wider (HR_R = 1.25; 95% CI, 1.01-1.55 and HR_P = 1.30; 95% CI, 0.83-2.01). For both carrier groups, alcohol consumption was not associated with breast cancer risk.

Conclusions

The finding that smoking during the prereproductive years increases breast cancer risk for mutation carriers warrants further investigation.

Impact

This is the largest prospective study of BRCA mutation carriers to assess these important risk factors.

SUBMITTER: Li H

PROVIDER: S-EPMC7611162 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Alcohol Consumption, Cigarette Smoking, and Risk of Breast Cancer for <i>BRCA1</i> and <i>BRCA2</i> Mutation Carriers: Results from The BRCA1 and BRCA2 Cohort Consortium.

Li Hongyan H Terry Mary Beth MB Antoniou Antonis C AC Phillips Kelly-Anne KA Kast Karin K Mooij Thea M TM Engel Christoph C Noguès Catherine C Stoppa-Lyonnet Dominique D Lasset Christine C Berthet Pascaline P Mari Veronique V Caron Olivier O Barrowdale Daniel D Frost Debra D Brewer Carole C Evans D Gareth DG Izatt Louise L Side Lucy L Walker Lisa L Tischkowitz Marc M Rogers Mark T MT Porteous Mary E ME Snape Katie K Meijers-Heijboer Hanne E J HEJ Gille Johan J P JJP Blok Marinus J MJ Hoogerbrugge Nicoline N Daly Mary B MB Andrulis Irene L IL Buys Saundra S SS John Esther M EM McLachlan Sue-Anne SA Friedlander Michael M Tan Yen Y YY Osorio Ana A Caldes Trinidad T Jakubowska Anna A Simard Jacques J Singer Christian F CF Olah Edith E Navratilova Marie M Foretova Lenka L Gerdes Anne-Marie AM Roos-Blom Marie-José MJ Arver Brita B Olsson Håkan H Schmutzler Rita K RK Hopper John L JL Milne Roger L RL Easton Douglas F DF Van Leeuwen Flora E FE Rookus Matti A MA Andrieu Nadine N Goldgar David E DE

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20191202 2

<h4>Background</h4>Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer, but very few studies have examined these effects in <i>BRCA1</i> and <i>BRCA2</i> mutation carriers. Given the high breast cancer risk for mutation carriers and the importance of <i>BRCA1</i> and <i>BRCA2</i> in DNA repair, better evidence on the associations of these lifestyle factors with breast cancer risk is essential.<h4>Met ...[more]

PMID: 31792088

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Project description:INTRODUCTION:Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. METHODS:We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS:The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. CONCLUSIONS:The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.