A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
Pooja Middha,
Xiaoliang Wang,
Sabine Behrens,
Manjeet K Bolla,
Qin Wang,
Joe Dennis,
Kyriaki Michailidou,
Thomas U Ahearn,
Irene L Andrulis,
Hoda Anton-Culver,
Volker Arndt,
Kristan J Aronson,
Paul L Auer,
Annelie Augustinsson,
Thaïs Baert,
Laura E Beane Freeman,
Heiko Becher,
Matthias W Beckmann,
Javier Benitez,
Stig E Bojesen,
Hiltrud Brauch,
Hermann Brenner,
Angela Brooks-Wilson,
Daniele Campa,
Federico Canzian,
Angel Carracedo,
Jose E Castelao,
Stephen J Chanock,
Georgia Chenevix-Trench,
,
Emilie Cordina-Duverger,
Fergus J Couch,
Angela Cox,
Simon S Cross,
Kamila Czene,
Laure Dossus,
Pierre-Antoine Dugué,
A Heather Eliassen,
Mikael Eriksson,
D Gareth Evans,
Peter A Fasching,
Jonine D Figueroa,
Olivia Fletcher,
Henrik Flyger,
Marike Gabrielson,
Manuela Gago-Dominguez,
Graham G Giles,
Anna González-Neira,
Felix Grassmann,
Anne Grundy,
Pascal Guénel,
Christopher A Haiman,
Niclas Håkansson,
Per Hall,
Ute Hamann,
Susan E Hankinson,
Elaine F Harkness,
Bernd Holleczek,
Reiner Hoppe,
John L Hopper,
Richard S Houlston,
Anthony Howell,
David J Hunter,
Christian Ingvar,
,
,
Karolin Isaksson,
Helena Jernström,
Esther M John,
Michael E Jones,
Rudolf Kaaks,
Renske Keeman,
Cari M Kitahara,
Yon-Dschun Ko,
Stella Koutros,
Allison W Kurian,
James V Lacey,
Diether Lambrechts,
Nicole L Larson,
Susanna Larsson,
Loic Le Marchand,
Flavio Lejbkowicz,
Shuai Li,
Martha Linet,
Jolanta Lissowska,
Maria Elena Martinez,
Tabea Maurer,
Anna Marie Mulligan,
Claire Mulot,
Rachel A Murphy,
William G Newman,
Sune F Nielsen,
Børge G Nordestgaard,
Aaron Norman,
Katie M O'Brien,
Janet E Olson,
Alpa V Patel,
Ross Prentice,
Erika Rees-Punia,
Gad Rennert,
Valerie Rhenius,
Kathryn J Ruddy,
Dale P Sandler,
Christopher G Scott,
Mitul Shah,
Xiao-Ou Shu,
Ann Smeets,
Melissa C Southey,
Jennifer Stone,
Rulla M Tamimi,
Jack A Taylor,
Lauren R Teras,
Katarzyna Tomczyk,
Melissa A Troester,
Thérèse Truong,
Celine M Vachon,
Sophia S Wang,
Clarice R Weinberg,
Hans Wildiers,
Walter Willett,
Stacey J Winham,
Alicja Wolk,
Xiaohong R Yang,
M Pilar Zamora,
Wei Zheng,
Argyrios Ziogas,
Alison M Dunning,
Paul D P Pharoah,
Montserrat García-Closas,
Marjanka K Schmidt,
Peter Kraft,
Roger L Milne,
Sara Lindström,
Douglas F Easton,
Jenny Chang-Claude
Abstract
METHODS
Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.
CONCLUSIONS
Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.
RESULTS
Assuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94).
BACKGROUND
Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.