Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Barrdahl M, Rudolph A, Hopper JL, Southey MC, Broeks A, Fasching P, Beckmann M, Gago-Dominguez M, Castelao JE, Guenel P, Truong T, Bojesen SE, Gapstur SM, Gaudet MM, Brenner H, Arndt V, Brauch H, Hamann U, Mannermaa A, Lambrechts D, Jongen L, Flesch-Janys D, Thoene K, Couch FJ, Giles GG, Simard J, Goldberg MS, Figueroa J, Michailidou K, Bolla MK, Dennis J, Wang Q, Eilber U, Behrens S, Czene K, Hall P, Cox A, Cross S, Swerdlow A, Schoemaker MJ, Dunning AM, Kaaks R, Pharoah PDP, Schmidt M, Garcia-Closas M, Easton DF, Milne RL, Chang-Claude J
Zeitschrift: International Journal of Cancer
Jahr der Veröffentlichung: 2017
Band: 141
Heftnummer: 9
Seitenbereich: 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 single nucleotide polymorphisms 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 and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER 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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Einrichtungen weiterer Autorinnen und Autoren

American Cancer Society
Antoni van Leeuwenhoek
Complejo Hospitalario Universitario de Santiago de Compostela
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
École Polytechnique - Université Paris-Saclay
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Mayo Clinic
McGill University
National Cancer Institute (NCI)
Servizo Galego de Saúde
The Institute of Cancer Research (ICR)
The University of Melbourne
Universitätsklinikum Hamburg-Eppendorf (UKE)
Université Laval (UL)
University of Cambridge
University of Eastern Finland
University of Edinburgh
University of Sheffield


Zitierweisen

APA:
Barrdahl, M., Rudolph, A., Hopper, J.L., Southey, M.C., Broeks, A., Fasching, P.,... Chang-Claude, J. (2017). Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium. International Journal of Cancer, 141(9), 1830-1840. https://dx.doi.org/10.1002/ijc.30859

MLA:
Barrdahl, Myrto, et al. "Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium." International Journal of Cancer 141.9 (2017): 1830-1840.

BibTeX: 

Zuletzt aktualisiert 2019-09-03 um 07:23