Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
Creators: name: Schoen, Robert E.
name: Bishop, D. Timothy
name: Wolk, Alicja
name: Keku, Temitope O.
name: Díez-Obrero, Virginia
name: Brenner, Hermann
name: Chen, Rui
name: Tsilidis, Konstantinos K.
name: Gunter, Marc J.
name: Sakoda, Lori C.
name: Hidaka, Akihisa
name: Giles, Graham G.
name: Harrison, Tabitha A.
name: Tian, Yu
name: Jordahl, Kristina M.
name: Budiarto, Arif
name: Woods, Michael O.
name: Ruiz-Narvaez, Edward A.
name: Qu, Conghui
name: Chen, Xuechen
name: Thibodeau, Stephen N.
name: Rennert, Gad
name: White, Emily
name: Berndt, Sonja I.
name: Visvanathan, Kala
name: Casey, Graham
name: Buchanan, Daniel D.
name: Hsu, Li
name: Joshi, Amit D.
name: Van Guelpen, Bethany
name: Chan, Andrew T.
name: Peoples, Anita R.
name: Li, Li
name: Lin, Yi
name: Pardamean, Bens
name: Kawaguchi, Eric
name: Campbell, Peter T.
name: van Duijnhoven, Franzel J. B.
name: Pellatt, Andrew J.
name: Gauderman, W. James
name: Nan, Hongmei
name: Arndt, Volker
name: Peters, Ulrike
name: Hoffmeister, Michael
name: Ose, Jennifer
name: Chang-Claude, Jenny
name: Prentice, Ross L.
name: Larsson, Susanna C.
name: Ogino, Shuji
name: Nassir, Rami
name: Gallinger, Steven
name: Moreno, Victor
name: Figueiredo, Jane C.
name: Obón-Santacana, Mireia
name: Baurley, James W.
name: Kundaje, Anshul
name: Thomas, Duncan C.
name: Lewinger, Juan Pablo
name: Harlid, Sophia
name: Platz, Elizabeth A.
name: Carreras-Torres, Robert
name: Wu, Anna H.
name: Conti, David V.
name: Jenkins, Mark A.
name: Su, Yu-Ru
name: Drew, David A.
name: Kim, Andre E.
name: Murphy, Neil
name: Marchand, Loic Le
name: Huyghe, Jeroen R.
name: Dimou, Niki
name: Stern, Mariana C.
name: Bien, Stephanie A.
name: Newcomb, Polly A.
name: Shcherbina, Anna
name: Potter, John D.
name: Gruber, Stephen B.
name: Morrison, John
Publisher: name: Springer Nature
Year: 2024

description: <p>BackgroundMenopausal 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.MethodsWe 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.ResultsThe 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&thinsp;=&thinsp;2.7 &times;&thinsp;10&minus;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%&ndash;4.0%) vs 6.1% (5.7%&ndash;6.5%) (difference 2.4%, P-value&thinsp;=&thinsp;1.83 &times;&thinsp;10&minus;14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%&ndash;1.8%) vs 2.2% (1.9%&ndash;2.4%) (difference 0.6%, P-value&thinsp;=&thinsp;1.01 &times;&thinsp;10&minus;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.ConclusionsMHT 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.</p>