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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk

  • Background: Menopausal 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. Methods: 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. Results: 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. Conclusions: 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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Author:Yu TianORCiD, Yi Lin, Conghui Qu, Volker ArndtORCiD, James W. Baurley, Sonja I. Berndt, Stephanie A. Bien, D. Timothy BishopORCiD, Hermann BrennerORCiD, Daniel D. BuchananORCiD, Arif Budiarto, Peter T. Campbell, Robert Carreras-TorresORCiD, Graham Casey, Andrew T. ChanORCiD, Rui Chen, Xuechen ChenORCiD, David V. ContiORCiD, Virginia Díez-Obrero, Niki Dimou, David A. Drew, Jane C. Figueiredo, Steven Gallinger, Graham G. Giles, Stephen B. GruberORCiD, Marc J. Gunter, Sophia Harlid, Tabitha A. Harrison, Akihisa Hidaka, Michael HoffmeisterORCiD, Jeroen R. HuygheORCiD, Mark A. Jenkins, Kristina M. Jordahl, Amit D. Joshi, Temitope O. Keku, Eric Kawaguchi, Andre E. Kim, Anshul Kundaje, Susanna C. LarssonORCiD, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Victor MorenoORCiD, John Morrison, Neil MurphyORCiD, Hongmei Nan, Rami Nassir, Polly A. NewcombORCiD, Mireia Obón-Santacana, Shuji OginoORCiD, Jennifer OseORCiDGND, Bens PardameanORCiD, Andrew J. PellattORCiD, Anita R. Peoples, Elizabeth A. PlatzORCiD, John D. Potter, Ross L. Prentice, Gad Rennert, Edward A. Ruiz-NarvaezORCiD, Lori C. Sakoda, Robert E. Schoen, Anna Shcherbina, Mariana C. Stern, Yu-Ru Su, Stephen N. Thibodeau, Duncan C. Thomas, Konstantinos K. Tsilidis, Fränzel J. B. van Duijnhoven, Bethany van Guelpen, Kala VisvanathanORCiD, Emily White, Alicja WolkORCiD, Michael O. Woods, Anna H. Wu, Ulrike Peters, W. James Gauderman, Li HsuORCiD, Jenny Chang-ClaudeORCiD
URN:urn:nbn:de:bsz:960-opus4-30989
DOI:https://doi.org/10.25968/opus-3098
DOI original:https://doi.org/10.1038/s41416-024-02638-2
ISSN:0007-0920
Parent Title (English):British Journal of Cancer
Document Type:Article
Language:English
Year of Completion:2024
Publishing Institution:Hochschule Hannover
Release Date:2024/05/21
GND Keyword:Dickdarmkrebs; Krebsrisiko; Menopause; Hormontherapie
Page Number:10
Institutes:Fakultät III - Medien, Information und Design
DDC classes:610 Medizin, Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International