Barrdahl, M. orcid.org/0000-0003-4661-0763, Rudolph, A. orcid.org/0000-0001-7520-2035, Hopper, J.L. et al. (45 more authors) (2017) Gene-environment interactions involving functional variants: results from the Breast Cancer Association Consortium. International Journal of Cancer, 141 (9). pp. 1830-1840. ISSN 0020-7136
Abstract
Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions.
We assessed the interplay between 70 SNPs identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases, 31,605 controls) from the Breast Cancer Association Consortium (BCAC), in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor positive (ER+) and estrogen receptor negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results.
Four potential gene-environment interactions were identified as noteworthy (BFDP<0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint =0.77, 95% CI: 0.67-0.88, Pint =1.8 × 10(-4) ). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16-1.59, Pint =1.9 × 10(-5) ) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint =1.26, 95% CI: 1.12-1.43, Pint =1.8 × 10(-4) ) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint =0.89, 95% CI: 0.83-0.95, Pint =5.2 × 10(-4) ).
While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed. This article is protected by copyright. All rights reserved.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
Keywords: | breast cancer; SNP; BCAC; gene-environment; interaction |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Funding Information: | Funder Grant number YORKSHIRE CANCER RESEARCH S299 BREAST CANCER CAMPAIGN UNSPECIFIED CANCER RESEARCH UK (CRUK) C5410/A7315. CANCER RESEARCH UK (CRUK) C9267/A25152 BREAST CANCER CAMPAIGN UNSPECIFIED BREAST CANCER NOW UNSPECIFIED BREAST CANCER NOW UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Jul 2017 14:42 |
Last Modified: | 18 Oct 2023 11:55 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ijc.30859 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118799 |