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Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.
- Tian, Yu;
- Kim, Andre E;
- Bien, Stephanie A;
- Lin, Yi;
- Qu, Conghui;
- Harrison, Tabitha A;
- Carreras-Torres, Robert;
- Díez-Obrero, Virginia;
- Dimou, Niki;
- Drew, David A;
- Hidaka, Akihisa;
- Huyghe, Jeroen R;
- Jordahl, Kristina M;
- Morrison, John;
- Murphy, Neil;
- Obón-Santacana, Mireia;
- Ulrich, Cornelia M;
- Ose, Jennifer;
- Peoples, Anita R;
- Ruiz-Narvaez, Edward A;
- Shcherbina, Anna;
- Stern, Mariana C;
- Su, Yu-Ru;
- van Duijnhoven, Franzel JB;
- Arndt, Volker;
- Baurley, James W;
- Berndt, Sonja I;
- Bishop, D Timothy;
- Brenner, Hermann;
- Buchanan, Daniel D;
- Chan, Andrew T;
- Figueiredo, Jane C;
- Gallinger, Steven;
- Gruber, Stephen B;
- Harlid, Sophia;
- Hoffmeister, Michael;
- Jenkins, Mark A;
- Joshi, Amit D;
- Keku, Temitope O;
- Larsson, Susanna C;
- Le Marchand, Loic;
- Li, Li;
- Giles, Graham G;
- Milne, Roger L;
- Nan, Hongmei;
- Nassir, Rami;
- Ogino, Shuji;
- Budiarto, Arif;
- Platz, Elizabeth A;
- Potter, John D;
- Prentice, Ross L;
- Rennert, Gad;
- Sakoda, Lori C;
- Schoen, Robert E;
- Slattery, Martha L;
- Thibodeau, Stephen N;
- Van Guelpen, Bethany;
- Visvanathan, Kala;
- White, Emily;
- Wolk, Alicja;
- Woods, Michael O;
- Wu, Anna H;
- Campbell, Peter T;
- Casey, Graham;
- Conti, David V;
- Gunter, Marc J;
- Kundaje, Anshul;
- Lewinger, Juan Pablo;
- Moreno, Victor;
- Newcomb, Polly A;
- Pardamean, Bens;
- Thomas, Duncan C;
- Tsilidis, Konstantinos K;
- Peters, Ulrike;
- Gauderman, W James;
- Hsu, Li;
- Chang-Claude, Jenny
Published Web Location
https://doi.org/10.1093/jnci/djac094Abstract
Background
The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.Methods
We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants.Results
The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4).Conclusion
Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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