CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk

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Author
Garcia-Albeniz, Xabier
Rudolph, Anja
Hutter, Carolyn
White, Emily
Lin, Yi
Rosse, Stephanie A
Figueiredo, Jane C
Harrison, Tabitha A
Jiao, Shuo
Brenner, Hermann
Casey, Graham
Hudson, Thomas J
Thornquist, Mark
Le Marchand, Loic
Potter, John
Slattery, Martha L
Zanke, Brent
Baron, John A
Caan, Bette J
Chanock, Stephen J
Berndt, Sonja I
Stelling, Deanna
Hoffmeister, Michael
Butterbach, Katja
Du, Mengmeng
James Gauderman, W
Gunter, Marc J
Lemire, Mathieu
Lin, Jennifer
Hayes, Richard B
Haile, Robert W
Schoen, Robert E
Warnick, Greg S
Jenkins, Mark A
Thibodeau, Stephen N
Schumacher, Fredrick R
Lindor, Noralane M
Kolonel, Laurence N
Hopper, John L
Gong, Jian
Seminara, Daniela
Pflugeisen, Bethann M
Ulrich, Cornelia M
Qu, Conghui
Duggan, David
Cotterchio, Michelle
Campbell, Peter T
Carlson, Christopher S
Newcomb, Polly A
Hsu, Li
Peters, Ulrike
Chang-Claude, Jenny
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/bjc.2015.443Metadata
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Garcia-Albeniz, X., A. Rudolph, C. Hutter, E. White, Y. Lin, S. A. Rosse, J. C. Figueiredo, et al. 2016. “CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.” British Journal of Cancer 114 (2): 221-229. doi:10.1038/bjc.2015.443. http://dx.doi.org/10.1038/bjc.2015.443.Abstract
Background: Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene–environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT. Methods: We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen–progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case–control logistic regression as primary tests. The Cocktail test was used as secondary test. Results: The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52–0.72), P=4.8 × 10−9). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52–0.78), P=1.2 × 10−5 (alpha threshold=3.1 × 10−4). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61–1.50); A/C, 0.61 (0.39–0.95) and A/A, 0.40 (0.22–0.73), respectively. Conclusions: Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815813/pdf/Terms of Use
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