A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
Middha P., Wang X., Behrens S., Bolla MK., Wang Q., Dennis J., Michailidou K., Ahearn TU., Andrulis IL., Anton-Culver H., Arndt V., Aronson KJ., Auer PL., Augustinsson A., Baert T., Freeman LEB., Becher H., Beckmann MW., Benitez J., Bojesen SE., Brauch H., Brenner H., Brooks-Wilson A., Campa D., Canzian F., Carracedo A., Castelao JE., Chanock SJ., Chenevix-Trench G., CTS Consortium None., Cordina-Duverger E., Couch FJ., Cox A., Cross SS., Czene K., Dossus L., Dugué P-A., Eliassen AH., Eriksson M., Evans DG., Fasching PA., Figueroa JD., Fletcher O., Flyger H., Gabrielson M., Gago-Dominguez M., Giles GG., González-Neira A., Grassmann F., Grundy A., Guénel P., Haiman CA., Håkansson N., Hall P., Hamann U., Hankinson SE., Harkness EF., Holleczek B., Hoppe R., Hopper JL., Houlston RS., Howell A., Howell A., Hunter DJ., Ingvar C., ABCTB Investigators None., kConFab Investigators None., Isaksson K., Jernström H., John EM., Jones ME., Kaaks R., Keeman R., Kitahara CM., Ko Y-D., Koutros S., Kurian AW., Lacey JV., Lambrechts D., Larson NL., Larsson S., Le Marchand L., Lejbkowicz F., Li S., Linet M., Lissowska J., Martinez ME., Maurer T., Mulligan AM., Mulot C., Murphy RA., Newman WG., Nielsen SF., Nordestgaard BG., Norman A., O'Brien KM., Olson JE., Patel AV., Prentice R., Rees-Punia E., Rennert G., Rhenius V., Ruddy KJ., Sandler DP., Scott CG., Shah M., Shu X-O., Smeets A., Southey MC., Stone J., Tamimi RM., Taylor JA., Teras LR., Tomczyk K., Troester MA., Truong T., Vachon CM., Wang SS., Weinberg CR., Wildiers H., Willett W., Winham SJ., Wolk A., Yang XR., Zamora MP., Zheng W., Ziogas A., Dunning AM., Pharoah PDP., García-Closas M., Schmidt MK., Kraft P., Milne RL., Lindström S., Easton DF., Chang-Claude J.
BackgroundGenome-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.MethodsAnalyses 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.ResultsAssuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability int = 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).ConclusionsOverall, 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.