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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

  • Middha, Pooja K;
  • Wang, Xiaoliang;
  • Behrens, Sabine;
  • Bolla, Manjeet K;
  • Wang, Qin;
  • Dennis, Joe;
  • Michailidou, Kyriaki;
  • Ahearn, Thomas U;
  • Andrulis, Irene L;
  • Anton-Culver, Hoda;
  • Arndt, Volker;
  • Aronson, Kristan J;
  • Auer, Paul L;
  • Augustinsson, Annelie;
  • Baert, Thais; 100986;
  • Freeman, Laura E Beane;
  • Becher, Heiko;
  • Beckmann, Matthias W;
  • Benitez, Javier;
  • Bojesen, Stig E;
  • And 112 more
Publication Date
Aug 09, 2023
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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. 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. 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). 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. / status: published

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