Journal Article

DKFZ-2024-00634

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

Tian, Y. (First author)DKFZ* ; Lin, Y. ; Qu, C. ; Arndt, V.DKFZ* ; Baurley, J. W. ; Berndt, S. I. ; Bien, S. A. ; Bishop, D. T. ; Brenner, H.DKFZ* ; Buchanan, D. D. ; Budiarto, A. ; Campbell, P. T. ; Carreras-Torres, R. ; Casey, G. ; Chan, A. T. ; Chen, R. ; Chen, X.DKFZ* ; Conti, D. V. ; Díez-Obrero, V. ; Dimou, N. ; Drew, D. A. ; Figueiredo, J. C. ; Gallinger, S. ; Giles, G. G. ; Gruber, S. B. ; Gunter, M. J. ; Harlid, S. ; Harrison, T. A. ; Hidaka, A. ; Hoffmeister, M.DKFZ* ; Huyghe, J. R. ; Jenkins, M. A. ; Jordahl, K. M. ; Joshi, A. D. ; Keku, T. O. ; Kawaguchi, E. ; Kim, A. E. ; Kundaje, A. ; Larsson, S. C. ; Marchand, L. L. ; Lewinger, J. P. ; Li, L. ; Moreno, V. ; Morrison, J. ; Murphy, N. ; Nan, H. ; Nassir, R. ; Newcomb, P. A. ; Obón-Santacana, M. ; Ogino, S. ; Ose, J. ; Pardamean, B. ; Pellatt, A. J. ; Peoples, A. R. ; Platz, E. A. ; Potter, J. D. ; Prentice, R. L. ; Rennert, G. ; Ruiz-Narvaez, E. A. ; Sakoda, L. C. ; Schoen, R. E. ; Shcherbina, A. ; Stern, M. C. ; Su, Y.-R. ; Thibodeau, S. N. ; Thomas, D. C. ; Tsilidis, K. K. ; van Duijnhoven, F. J. B. ; Van Guelpen, B. ; Visvanathan, K. ; White, E. ; Wolk, A. ; Woods, M. O. ; Wu, A. H. ; Peters, U. ; Gauderman, W. J. ; Hsu, L. ; Chang-Claude, J. (Last author)DKFZ*

2024
Nature Publ. Group Edinburgh

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Please use a persistent id in citations: doi:10.1038/s41416-024-02638-2

Abstract: 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.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.

Note: #EA:C020#LA:C020# / 2024 Jun;130(10):1687-1696

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. C071 Cancer Survivorship (C071)
4. Präventive Onkologie (C120)
5. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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