Identification of new genetic susceptibility Loci for breast cancer through consideration of gene-environment interactions

Schoeps A, Rudolph A, Seibold P, Dunning AM, Milne RL, Bojesen SE, Swerdlow A, Andrulis I, Brenner H, Behrens S, Orr N, Jones M, Ashworth A, Li J, Cramp H, Connley D, Czene K, Darabi H, Chanock SJ, Lissowska J, Figueroa JD, Knight J, Glendon G, Mulligan AM, Dumont M, Severi G, Baglietto L, Olson J, Vachon C, Purrington K, Moisse M, Neven P, Wildiers H, Spurdle A, Kosma VM, Kataja V, Hartikainen JM, Hamann U, Ko YD, Dieffenbach AK, Arndt V, Stegmaier C, Malats N, Arias Perez JI, Benitez J, Flyger H, Nordestgaard BG, Truong T, Cordina-Duverger E, Menegaux F, Dos Santos Silva I, Fletcher O, Johnson N, Häberle L, Beckmann M, Ekici AB, Braaf L, Atsma F, Van Den Broek AJ, Makalic E, Schmidt DF, Southey MC, Cox A, Simard J, Giles GG, Lambrechts D, Mannermaa A, Brauch H, Guenel P, Peto J, Fasching P, Hopper J, Flesch-Janys D, Couch F, Chenevix-Trench G, Pharoah PDP, Garcia-Closas M, Schmidt MK, Hall P, Easton DF, Chang-Claude J (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: Wiley-Blackwell

Book Volume: 38

Pages Range: 84-93

Journal Issue: 1

DOI: 10.1002/gepi.21771

Abstract

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07) ), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05) ). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.

Authors with CRIS profile

Involved external institutions

Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) National Cancer Institute (NCI) United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Cambridge United Kingdom (GB) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Copenhagen University Hospital Denmark (DK) Mount Sinai Hospital (MSH) Canada (CA) Genome Institute of Singapore Singapore (SG) University of Sheffield United Kingdom (GB) Karolinska Institute Sweden (SE) University Health Network (UHN) Canada (CA) Université Laval (UL) Canada (CA) Cancer Council Victoria Australia (AU) Mayo Clinic United States (USA) (US) University of Eastern Finland Finland (FI) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Hospital Monte Naranco Spain (ES) University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud France (FR) London School of Hygiene and Tropical Medicine United Kingdom (GB) Netherlands Cancer Institute (NKI) Netherlands (NL) Sanquin Bloedbank Nijmegen Germany (DE) The University of Melbourne Australia (AU) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Robert-Bosch-Krankenhaus Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE)

How to cite

APA:

Schoeps, A., Rudolph, A., Seibold, P., Dunning, A.M., Milne, R.L., Bojesen, S.E.,... Chang-Claude, J. (2014). Identification of new genetic susceptibility Loci for breast cancer through consideration of gene-environment interactions. Genetic Epidemiology, 38(1), 84-93. https://dx.doi.org/10.1002/gepi.21771

MLA:

Schoeps, Anja, et al. "Identification of new genetic susceptibility Loci for breast cancer through consideration of gene-environment interactions." Genetic Epidemiology 38.1 (2014): 84-93.

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