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000180090 1001_ $$0P:(DE-He78)834e8bc4d74592e3b999100c157215f5$$aTian, Yu$$b0$$eFirst author$$udkfz
000180090 245__ $$aGenome-Wide Interaction Analysis of Genetic Variants with Menopausal Hormone Therapy for Colorectal Cancer Risk.
000180090 260__ $$aOxford$$bOxford Univ. Press$$c2022
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000180090 500__ $$a#EA:C020#LA:C020#  / 2022 Aug 8;114(8):1135-1148
000180090 520__ $$aThe use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.We conducted a genome-wide gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen-only, and combined estrogen-progestogen therapy with CRC risk, among 28,486 postmenopausal women (11,519 cases and 16,967 controls) from 38 studies, using logistic regression, two-step method, and 2- or 3-degree-of-freedom (d.f.) joint test. A set-based score test was applied for rare genetic variants.The use of any MHT, estrogen-only and estrogen-progestogen were associated with a reduced CRC risk [odds ratio (OR) with 95% confidence interval (95% CI) of 0.71 (0.64-0.78), 0.65 (0.53-0.79), and 0.73 (0.59-0.90), respectively]. The two-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was significantly reduced in women with the GG genotype [0.68 (0.64-0.72)] but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-d.f. joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing ORs of 0.78 (0.70-0.87) for TT, 0.68 (0.63-0.73) for TC, and 0.66 (0.60-0.74) for CC genotypes. In addition, five genes in rare variant analysis showed suggestive interactions with MHT (two-sided P < 1.2x10-4).Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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000180090 7001_ $$aKim, Andre E$$b1
000180090 7001_ $$aBien, Stephanie A$$b2
000180090 7001_ $$aLin, Yi$$b3
000180090 7001_ $$aQu, Conghui$$b4
000180090 7001_ $$aHarrison, Tabitha$$b5
000180090 7001_ $$aCarreras-Torres, Robert$$b6
000180090 7001_ $$aDíez-Obrero, Virginia$$b7
000180090 7001_ $$aDimou, Niki$$b8
000180090 7001_ $$aDrew, David A$$b9
000180090 7001_ $$aHidaka, Akihisa$$b10
000180090 7001_ $$aHuyghe, Jeroen R$$b11
000180090 7001_ $$aJordahl, Kristina M$$b12
000180090 7001_ $$aMorrison, John$$b13
000180090 7001_ $$aMurphy, Neil$$b14
000180090 7001_ $$aObón-Santacana, Mireia$$b15
000180090 7001_ $$aUlrich, Cornelia M$$b16
000180090 7001_ $$aOse, Jennifer$$b17
000180090 7001_ $$aPeoples, Anita R$$b18
000180090 7001_ $$aRuiz-Narvaez, Edward A$$b19
000180090 7001_ $$aShcherbina, Anna$$b20
000180090 7001_ $$aStern, Mariana$$b21
000180090 7001_ $$aSu, Yu-Ru$$b22
000180090 7001_ $$avan Duijnhoven, Franzel J B$$b23
000180090 7001_ $$0P:(DE-He78)d023fdf423d87ee6c710e34dd7581fa0$$aArndt, Volker$$b24$$udkfz
000180090 7001_ $$aBaurley, James$$b25
000180090 7001_ $$aBerndt, Sonja I$$b26
000180090 7001_ $$aBishop, D Timothy$$b27
000180090 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b28$$udkfz
000180090 7001_ $$aBuchanan, Daniel D$$b29
000180090 7001_ $$aChan, Andrew T$$b30
000180090 7001_ $$aFigueiredo, Jane C$$b31
000180090 7001_ $$aGallinger, Steven$$b32
000180090 7001_ $$aGruber, Stephen B$$b33
000180090 7001_ $$aHarlid, Sophia$$b34
000180090 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b35$$udkfz
000180090 7001_ $$aJenkins, Mark A$$b36
000180090 7001_ $$aJoshi, Amit D$$b37
000180090 7001_ $$aKeku, Temitope O$$b38
000180090 7001_ $$aLarsson, Susanna C$$b39
000180090 7001_ $$aLe Marchand, Loic$$b40
000180090 7001_ $$aLi, Li$$b41
000180090 7001_ $$aGiles, Graham G$$b42
000180090 7001_ $$aMilne, Roger L$$b43
000180090 7001_ $$aNan, Hongmei$$b44
000180090 7001_ $$aNassir, Rami$$b45
000180090 7001_ $$aOgino, Shuji$$b46
000180090 7001_ $$aBudiarto, Arif$$b47
000180090 7001_ $$aPlatz, Elizabeth A$$b48
000180090 7001_ $$aPotter, John D$$b49
000180090 7001_ $$aPrentice, Ross L$$b50
000180090 7001_ $$aRennert, Gad$$b51
000180090 7001_ $$aSakoda, Lori C$$b52
000180090 7001_ $$aSchoen, Robert E$$b53
000180090 7001_ $$aSlattery, Martha L$$b54
000180090 7001_ $$aThibodeau, Stephen N$$b55
000180090 7001_ $$aVan Guelpen, Bethany$$b56
000180090 7001_ $$aVisvanathan, Kala$$b57
000180090 7001_ $$aWhite, Emily$$b58
000180090 7001_ $$aWolk, Alicja$$b59
000180090 7001_ $$aWoods, Michael O$$b60
000180090 7001_ $$aWu, Anna H$$b61
000180090 7001_ $$aCampbell, Peter T$$b62
000180090 7001_ $$aCasey, Graham$$b63
000180090 7001_ $$aConti, David V$$b64
000180090 7001_ $$aGunter, Marc J$$b65
000180090 7001_ $$aKundaje, Anshul$$b66
000180090 7001_ $$aLewinger, Juan Pablo$$b67
000180090 7001_ $$aMoreno, Victor$$b68
000180090 7001_ $$aNewcomb, Polly A$$b69
000180090 7001_ $$aPardamean, Bens$$b70
000180090 7001_ $$aThomas, Duncan C$$b71
000180090 7001_ $$aTsilidis, Konstantinos K$$b72
000180090 7001_ $$aPeters, Ulrike$$b73
000180090 7001_ $$aGauderman, W James$$b74
000180090 7001_ $$aHsu, Li$$b75
000180090 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b76$$eLast author$$udkfz
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