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Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium.


ABSTRACT: 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. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. 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.

SUBMITTER: Joshi AD 

PROVIDER: S-EPMC4224360 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium.

Joshi Amit D AD   Lindström Sara S   Hüsing Anika A   Barrdahl Myrto M   VanderWeele Tyler J TJ   Campa Daniele D   Canzian Federico F   Gaudet Mia M MM   Figueroa Jonine D JD   Baglietto Laura L   Berg Christine D CD   Buring Julie E JE   Chanock Stephen J SJ   Chirlaque María-Dolores MD   Diver W Ryan WR   Dossus Laure L   Giles Graham G GG   Haiman Christopher A CA   Hankinson Susan E SE   Henderson Brian E BE   Hoover Robert N RN   Hunter David J DJ   Isaacs Claudine C   Kaaks Rudolf R   Kolonel Laurence N LN   Krogh Vittorio V   Le Marchand Loic L   Lee I-Min IM   Lund Eiliv E   McCarty Catherine A CA   Overvad Kim K   Peeters Petra H PH   Riboli Elio E   Schumacher Fredrick F   Severi Gianluca G   Stram Daniel O DO   Sund Malin M   Thun Michael J MJ   Travis Ruth C RC   Trichopoulos Dimitrios D   Willett Walter C WC   Zhang Shumin S   Ziegler Regina G RG   Kraft Peter P  

American journal of epidemiology 20140925 10


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. We estimated t  ...[more]

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