Assessment of interactions between 205 breast cancer susceptibility loci and 13 established risk factors in relation to breast cancer risk, in the Breast Cancer Association Consortium

Research output: Contribution to journalArticle

Abstract

Background: Previous gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions. Methods: Analyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions. Results: Noteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth. Conclusions: Overall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

Details

Authors
Organisations
External organisations
  • German Cancer Research Centre
  • Heidelberg University
  • University of Washington
  • Fred Hutchinson Cancer Research Center
  • University of Cambridge
  • Cyprus Institute of Neurology and Genetics
  • Antoni Van Leeuwenhoek Hospital
  • Harvard University
  • National Cancer Institute, USA
  • Institute of Cancer Research London
  • Cancer Council Victoria
  • Monash University
  • University Medical Center Hamburg-Eppendorf
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Breast cancer, Epidemiology, Europeans, Gene-environment interaction, Risk factors, Single nucleotide polymorphism
Original languageEnglish
Pages (from-to)216-232
Number of pages17
JournalInternational Journal of Epidemiology
Volume49
Issue number1
Publication statusPublished - 2020 Feb 1
Publication categoryResearch
Peer-reviewedYes