TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Tian, Yu
A1  - Lin, Yi
A1  - Qu, Conghui
A1  - Arndt, Volker
A1  - Baurley, James W.
A1  - Berndt, Sonja I.
A1  - Bien, Stephanie A.
A1  - Bishop, D. Timothy
A1  - Brenner, Hermann
A1  - Buchanan, Daniel D.
A1  - Budiarto, Arif
A1  - Campbell, Peter T.
A1  - Carreras-Torres, Robert
A1  - Casey, Graham
A1  - Chan, Andrew T.
A1  - Chen, Rui
A1  - Chen, Xuechen
A1  - Conti, David V.
A1  - Díez-Obrero, Virginia
A1  - Dimou, Niki
A1  - Drew, David A.
A1  - Figueiredo, Jane C.
A1  - Gallinger, Steven
A1  - Giles, Graham G.
A1  - Gruber, Stephen B.
A1  - Gunter, Marc J.
A1  - Harlid, Sophia
A1  - Harrison, Tabitha A.
A1  - Hidaka, Akihisa
A1  - Hoffmeister, Michael
A1  - Huyghe, Jeroen R.
A1  - Jenkins, Mark A.
A1  - Jordahl, Kristina M.
A1  - Joshi, Amit D.
A1  - Keku, Temitope O.
A1  - Kawaguchi, Eric
A1  - Kim, Andre E.
A1  - Kundaje, Anshul
A1  - Larsson, Susanna C.
A1  - Marchand, Loic Le
A1  - Lewinger, Juan Pablo
A1  - Li, Li
A1  - Moreno, Victor
A1  - Morrison, John
A1  - Murphy, Neil
A1  - Nan, Hongmei
A1  - Nassir, Rami
A1  - Newcomb, Polly A.
A1  - Obón-Santacana, Mireia
A1  - Ogino, Shuji
A1  - Ose, Jennifer
A1  - Pardamean, Bens
A1  - Pellatt, Andrew J.
A1  - Peoples, Anita R.
A1  - Platz, Elizabeth A.
A1  - Potter, John D.
A1  - Prentice, Ross L.
A1  - Rennert, Gad
A1  - Ruiz-Narvaez, Edward A.
A1  - Sakoda, Lori C.
A1  - Schoen, Robert E.
A1  - Shcherbina, Anna
A1  - Stern, Mariana C.
A1  - Su, Yu-Ru
A1  - Thibodeau, Stephen N.
A1  - Thomas, Duncan C.
A1  - Tsilidis, Konstantinos K.
A1  - Duijnhoven, Fränzel J. B. van
A1  - Guelpen, Bethany van
A1  - Visvanathan, Kala
A1  - White, Emily
A1  - Wolk, Alicja
A1  - Woods, Michael O.
A1  - Wu, Anna H.
A1  - Peters, Ulrike
A1  - Gauderman, W. James
A1  - Hsu, Li
A1  - Chang-Claude, Jenny
T1  - Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
JF  - British Journal of Cancer
N2  - 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.
KW  - Dickdarmkrebs
KW  - Krebsrisiko
KW  - Menopause
KW  - Hormontherapie
Y1  - 2024
UN  - https://nbn-resolving.org/urn:nbn:de:bsz:960-opus4-30989
SN  - 0007-0920
SS  - 0007-0920
U6  - https://doi.org/10.25968/opus-3098
DO  - https://doi.org/10.25968/opus-3098
SP  - 10
S1  - 10
ER  -