Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. ⋯ After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
Amit D Joshi, Sara Lindström, Anika Hüsing, Myrto Barrdahl, Tyler J VanderWeele, Daniele Campa, Federico Canzian, Mia M Gaudet, Jonine D Figueroa, Laura Baglietto, Christine D Berg, Julie E Buring, Stephen... more J Chanock, María-Dolores Chirlaque, W Ryan Diver, Laure Dossus, Graham G Giles, Christopher A Haiman, Susan E Hankinson, Brian E Henderson, Robert N Hoover, David J Hunter, Claudine Isaacs, Rudolf Kaaks, Laurence N Kolonel, Vittorio Krogh, Loic Le Marchand, I-Min Lee, Eiliv Lund, Catherine A McCarty, Kim Overvad, Petra H Peeters, Elio Riboli, Fredrick Schumacher, Gianluca Severi, Daniel O Stram, Malin Sund, Michael J Thun, Ruth C Travis, Dimitrios Trichopoulos, Walter C Willett, Shumin Zhang, Regina G Ziegler, Peter Kraft, and Breast and Prostate Cancer Cohort Consortium (BPC3). less