Abstract 4831: Additive and multiplicative gene-environment interactions for colorectal cancer risk

• Published in: Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.4831-4831
• Main Authors: Du, Mengmeng, Berndt, Sonja I., Brenner, Hermann, Caan, Bette J., Campbell, Peter T., Casey, Graham, Chan, Andrew, Chang-Claude, Jenny, Chanock, Stephen J., Chatterjee, Nilanjan, Conti, David V., Duggan, David, Figueiredo, Jane C., Gallinger, Steven, Gong, Jian, Haile, Robert W., Harrison, Tabitha A., Hayes, Richard B., Hoffmeister, Michael, Hopper, John L., Hsu, Li, Hudson, Thomas J., Hutter, Carolyn M., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Kolonel, Laurence N., Kraft, Peter, Le Marchand, Loic, Lemire, Mathieu, Lin, Yi, Lindor, Noralane M., Newcomb, Polly A., Potter, John D., Schoen, Robert E., Schumacher, Fredrick R., Seminara, Daniela, Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., Win, Aung Ko, White, Emily, Zanke, Brent W., Peters, Ulrike
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-4831

Background: Genetic and environmental factors influence colorectal cancer (CRC) risk. Previous studies have provided additional etiologic insight by examining multiplicative gene-environment interactions for individual susceptibility loci. However, individual loci confer only modest risks, which may limit statistical power and clinical significance. A genetic risk score comprising known CRC loci may provide a more comprehensive assessment of risk. Further, there is a paucity of data on the role of additive gene-environment interactions, which may have greater public health implications than multiplicative interactions. We thus evaluated both additive and multiplicative interactions between a genetic risk score and 15 key environmental factors on risk of CRC. Methods: We conducted an analysis of 10,491 CRC cases and 10,725 controls of European ancestry in 7 cohort and 6 case-control studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) or Colon Cancer Family Registry (CCFR). To provide a global measure of genetic predisposition, information across multiple risk variants was combined by calculating a genetic risk score based on 24 polymorphisms near 21 genetic loci identified in previous genome-wide association studies. For the genetic score and environmental factors, the reference category corresponded to that associated with lower CRC risk. We tested for additive interactions by estimating relative excess risk due to interactions (RERIs) using logistic regression; for multiplicative interactions we used an empirical-Bayes approach. Nominal P values ≤ 0.05 were considered statistically significant. Results: After adjustment for age, sex, center, study, principal components, and total energy, as appropriate, we observed super-additive gene-environment interactions for CRC risk between the genetic risk score and body mass index (RERI=0.15; 95% CI: 0.00-0.31), ever smoking (RERI=0.14; 95% CI: 0.00-0.28), pack-years of smoking (RERI=0.23; 95% CI: 0.05-0.41), postmenopausal hormone therapy use (RERI=0.38; 95% CI: 0.17-0.59), and intake of processed meat (RERI=0.23; 95% CI: 0.06-0.40). Of the 15 environmental risk factors, 12 showed RERIs > 0 – suggesting an overall trend toward super-additive interactions for these factors. In addition, we observed evidence of sub-multiplicative interactions for use of aspirin and non-steroidal anti-inflammatory drugs. There were no other statistically significant multiplicative interacti