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

Journal article

Publication Details

Author(s): 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
Journal: Genetic Epidemiology
Publisher: Wiley-Blackwell
Publication year: 2014
Volume: 38
Journal issue: 1
Pages range: 84-93
ISSN: 0741-0395


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.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

External institutions with authors

Cancer Council Victoria
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Genome Institute of Singapore
Hospital Monte Naranco
Karolinska Institute
Krebsregister Saarland / Saarland Cancer Registry
London School of Hygiene and Tropical Medicine
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
Netherlands Cancer Institute (NKI)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Sanquin Bloedbank Nijmegen
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
The University of Melbourne
Universitätsklinikum Hamburg-Eppendorf (UKE)
Université Laval (UL)
University Health Network (UHN)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Eastern Finland
University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud
University of Sheffield

How to cite

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.

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.


Last updated on 2019-21-07 at 08:08