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

Journal article


Publication Details

Author(s): 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
Journal: International Journal of Cancer
Publication year: 2015
Volume: 136
Journal issue: 6
Pages range: E685-96
ISSN: 0020-7136


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.



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

Antoni van Leeuwenhoek
Cancer Council Victoria
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Evangelische Kliniken Bonn gGmbH
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Genome Institute of Singapore
Hospital Monte Naranco
Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA)
Instituto de Investigación Sanitaria de Santiago de Compostela
Karolinska Institute
Krebsregister Saarland / Saarland Cancer Registry
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)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
The Alfred Hospital
The Institute of Cancer Research (ICR)
The University of Melbourne
Universidade de Santiago Compostela (USC)
Universitätsklinikum Hamburg-Eppendorf (UKE)
University Health Network (UHN)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Copenhagen
University of Eastern Finland
University of Sheffield
University of Vigo


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.

BibTeX: 

Last updated on 2019-21-07 at 07:58