Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

Rudolph A, Milne RL, Truong T, Knight JA, Seibold P, Flesch-Janys D, Behrens S, Eilber U, Bolla MK, Wang Q, Dennis J, Dunning AM, Shah M, Munday HR, Darabi H, Eriksson M, Brand JS, Olson J, Vachon CM, Hallberg E, Esteban Castelao J, Carracedo A, Torres M, Li J, Humphreys K, Cordina-Duverger E, Menegaux F, Flyger H, Nordestgaard BG, Nielsen SF, Yesilyurt BT, Floris G, Leunen K, Engelhardt EG, Broeks A, Rutgers EJ, Glendon G, Mulligan AM, Cross S, Reed M, Gonzalez-Neira A, Arias Perez JI, Provenzano E, Apicella C, Southey MC, Spurdle A, Haeberle L, Beckmann M, Ekici AB, Dieffenbach AK, Arndt V, Stegmaier C, Mclean C, Baglietto L, Chanock SJ, Lissowska J, Sherman ME, Bruening T, Hamann U, Ko YD, Orr N, Schoemaker M, Ashworth A, Kosma VM, Kataja V, Hartikainen JM, Mannermaa A, Swerdlow A, Giles GG, Brenner H, Fasching P, Chenevix-Trench G, Hopper J, Benitez J, Cox A, Andrulis IL, Lambrechts D, Gago-Dominguez M, Couch F, Czene K, Bojesen SE, Easton DF, Schmidt MK, Guenel P, Hall P, Pharoah PDP, Garcia-Closas M, Chang-Claude J (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 136

Pages Range: E685-96

Journal Issue: 6

DOI: 10.1002/ijc.29188

Abstract

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women >=170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

Authors with CRIS profile

Involved external institutions

Antoni van Leeuwenhoek Netherlands (NL) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Cancer Council Victoria Australia (AU) Mount Sinai Hospital (MSH) Canada (CA) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University of Cambridge United Kingdom (GB) Karolinska Institute Sweden (SE) Mayo Clinic United States (USA) (US) University of Vigo / Universidade de Vigo Spain (ES) Instituto de Investigación Sanitaria de Santiago de Compostela Spain (ES) Universidade de Santiago Compostela (USC) Spain (ES) Genome Institute of Singapore Singapore (SG) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Copenhagen University Hospital Denmark (DK) University of Copenhagen Denmark (DK) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) University Health Network (UHN) Canada (CA) University of Sheffield United Kingdom (GB) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Hospital Monte Naranco Spain (ES) The University of Melbourne Australia (AU) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) The Alfred Hospital Australia (AU) National Cancer Institute (NCI) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) Germany (DE) Evangelische Kliniken Bonn gGmbH Germany (DE) The Institute of Cancer Research (ICR) United Kingdom (GB) University of Eastern Finland Finland (FI)

How to cite

APA:

Rudolph, A., Milne, R.L., Truong, T., Knight, J.A., Seibold, P., Flesch-Janys, D.,... Chang-Claude, J. (2015). Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors. International Journal of Cancer, 136(6), E685-96. https://dx.doi.org/10.1002/ijc.29188

MLA:

Rudolph, Anja, et al. "Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors." International Journal of Cancer 136.6 (2015): E685-96.

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