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- Title
Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways.
- Authors
Amitay, Efrat L.; Carr, Prudence R.; Jansen, Lina; Alwers, Elizabeth; Roth, Wilfried; Herpel, Esther; Kloor, Matthias; Bläker, Hendrik; Chang‐Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael
- Abstract
Postmenopausal hormone replacement therapy (HRT) was found to be associated with lower risk of colorectal cancer (CRC). However, little is known regarding associations with molecular subtypes of CRC. The current study includes female participants of a large German population‐based case–control study (922 CRC cases and 1,183 controls). Tumor tissue samples were analyzed for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutation status. Multivariable logistic regression models were used to assess the association of HRT use with molecular subtypes and pathways. Postmenopausal HRT use was overall associated with reduced risk of CRC (adjusted odds ratio (aOR) 0.62, 95% confidence interval (CI) 0.50–0.76) and no major differences were observed for molecular subtypes or for tumor marker combinations representing molecular pathways. When stratified by median age (≤/>71 years) potentially stronger risk reductions were observed in the older group for subtypes showing MSI (OR = 0.36, 95% CI 0.17–0.76), BRAF mutation (OR = 0.40, 95% CI 0.30–0.83) and CIMP‐high (OR = 0.40, 95% CI 0.21–0.73) and for CRC suggestive of the sessile serrated pathway (OR = 0.45, 95% CI 0.20–1.01). In conclusion, postmenopausal use of HRT was similarly associated with risk reduction of major molecular tumor subtypes and pathways of CRC. Potentially stronger risk reductions with CRC subtypes diagnosed at higher ages require confirmation and clarification from other studies. The current study extends the limited understanding of the mechanisms of HRT in CRC prevention. What's new? Evidence suggests that among women, risk of colorectal cancer (CRC) may be reduced by hormone replacement therapy (HRT). Little is known, however, about the impact of HRT on the risk of specific CRC molecular subtypes. In this analysis of female study participants in Germany, postmenopausal use of HRT was associated with a reduction in risk of major molecular subtypes of CRC, namely those characterized by microsatellite instability, CpG island methylator phenotype, or BRAF or KRAS mutations. Risk reductions were strongest for CRC subtypes diagnosed at older ages. The findings expand upon current knowledge of HRT mechanisms in CRC prevention.
- Subjects
GERMANY; COLORECTAL cancer; HORMONE therapy; CANCER treatment; TUMOR markers; MOLECULAR association; HEREDITARY nonpolyposis colorectal cancer
- Publication
International Journal of Cancer, 2020, Vol 147, Issue 4, p1018
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.32868