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000289200 1001_ $$0P:(DE-He78)834e8bc4d74592e3b999100c157215f5$$aTian, Yu$$b0$$eFirst author
000289200 245__ $$aGenetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.
000289200 260__ $$aEdinburgh$$bNature Publ. Group$$c2024
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000289200 520__ $$aMenopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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000289200 7001_ $$aLin, Yi$$b1
000289200 7001_ $$aQu, Conghui$$b2
000289200 7001_ $$0P:(DE-He78)d023fdf423d87ee6c710e34dd7581fa0$$aArndt, Volker$$b3$$udkfz
000289200 7001_ $$aBaurley, James W$$b4
000289200 7001_ $$aBerndt, Sonja I$$b5
000289200 7001_ $$aBien, Stephanie A$$b6
000289200 7001_ $$00000-0002-8752-8785$$aBishop, D Timothy$$b7
000289200 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b8$$udkfz
000289200 7001_ $$00000-0003-2225-6675$$aBuchanan, Daniel D$$b9
000289200 7001_ $$aBudiarto, Arif$$b10
000289200 7001_ $$aCampbell, Peter T$$b11
000289200 7001_ $$00000-0002-2925-734X$$aCarreras-Torres, Robert$$b12
000289200 7001_ $$aCasey, Graham$$b13
000289200 7001_ $$00000-0001-7284-6767$$aChan, Andrew T$$b14
000289200 7001_ $$aChen, Rui$$b15
000289200 7001_ $$0P:(DE-He78)c392ec8a090dcfbe801f135a6212caf9$$aChen, Xuechen$$b16$$udkfz
000289200 7001_ $$00000-0002-2941-7833$$aConti, David V$$b17
000289200 7001_ $$aDíez-Obrero, Virginia$$b18
000289200 7001_ $$aDimou, Niki$$b19
000289200 7001_ $$aDrew, David A$$b20
000289200 7001_ $$aFigueiredo, Jane C$$b21
000289200 7001_ $$aGallinger, Steven$$b22
000289200 7001_ $$aGiles, Graham G$$b23
000289200 7001_ $$00000-0001-8656-7822$$aGruber, Stephen B$$b24
000289200 7001_ $$aGunter, Marc J$$b25
000289200 7001_ $$00000-0001-8540-6891$$aHarlid, Sophia$$b26
000289200 7001_ $$aHarrison, Tabitha A$$b27
000289200 7001_ $$aHidaka, Akihisa$$b28
000289200 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b29$$udkfz
000289200 7001_ $$00000-0001-6027-9806$$aHuyghe, Jeroen R$$b30
000289200 7001_ $$aJenkins, Mark A$$b31
000289200 7001_ $$aJordahl, Kristina M$$b32
000289200 7001_ $$aJoshi, Amit D$$b33
000289200 7001_ $$aKeku, Temitope O$$b34
000289200 7001_ $$aKawaguchi, Eric$$b35
000289200 7001_ $$aKim, Andre E$$b36
000289200 7001_ $$aKundaje, Anshul$$b37
000289200 7001_ $$00000-0003-0118-0341$$aLarsson, Susanna C$$b38
000289200 7001_ $$aMarchand, Loic Le$$b39
000289200 7001_ $$aLewinger, Juan Pablo$$b40
000289200 7001_ $$aLi, Li$$b41
000289200 7001_ $$00000-0002-2818-5487$$aMoreno, Victor$$b42
000289200 7001_ $$aMorrison, John$$b43
000289200 7001_ $$00000-0003-3347-8249$$aMurphy, Neil$$b44
000289200 7001_ $$aNan, Hongmei$$b45
000289200 7001_ $$00000-0001-9914-7851$$aNassir, Rami$$b46
000289200 7001_ $$00000-0001-8786-0043$$aNewcomb, Polly A$$b47
000289200 7001_ $$aObón-Santacana, Mireia$$b48
000289200 7001_ $$00000-0002-3909-2323$$aOgino, Shuji$$b49
000289200 7001_ $$aOse, Jennifer$$b50
000289200 7001_ $$00000-0002-7404-9005$$aPardamean, Bens$$b51
000289200 7001_ $$00000-0002-0127-9790$$aPellatt, Andrew J$$b52
000289200 7001_ $$aPeoples, Anita R$$b53
000289200 7001_ $$00000-0003-3676-8954$$aPlatz, Elizabeth A$$b54
000289200 7001_ $$aPotter, John D$$b55
000289200 7001_ $$aPrentice, Ross L$$b56
000289200 7001_ $$aRennert, Gad$$b57
000289200 7001_ $$00000-0002-0339-5824$$aRuiz-Narvaez, Edward A$$b58
000289200 7001_ $$aSakoda, Lori C$$b59
000289200 7001_ $$aSchoen, Robert E$$b60
000289200 7001_ $$aShcherbina, Anna$$b61
000289200 7001_ $$aStern, Mariana C$$b62
000289200 7001_ $$aSu, Yu-Ru$$b63
000289200 7001_ $$aThibodeau, Stephen N$$b64
000289200 7001_ $$aThomas, Duncan C$$b65
000289200 7001_ $$aTsilidis, Konstantinos K$$b66
000289200 7001_ $$avan Duijnhoven, Franzel J B$$b67
000289200 7001_ $$aVan Guelpen, Bethany$$b68
000289200 7001_ $$00000-0002-0582-8005$$aVisvanathan, Kala$$b69
000289200 7001_ $$aWhite, Emily$$b70
000289200 7001_ $$00000-0001-7387-6845$$aWolk, Alicja$$b71
000289200 7001_ $$aWoods, Michael O$$b72
000289200 7001_ $$aWu, Anna H$$b73
000289200 7001_ $$aPeters, Ulrike$$b74
000289200 7001_ $$aGauderman, W James$$b75
000289200 7001_ $$00000-0001-8168-4712$$aHsu, Li$$b76
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