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Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways
Author(s) -
Amitay Efrat L.,
Carr Prudence R.,
Jansen Lina,
Alwers Elizabeth,
Roth Wilfried,
Herpel Esther,
Kloor Matthias,
Bläker Hendrik,
ChangClaude Jenny,
Brenner Hermann,
Hoffmeister Michael
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32868
Subject(s) - microsatellite instability , colorectal cancer , kras , medicine , odds ratio , oncology , cancer , confidence interval , hormone replacement therapy (female to male) , population , bioinformatics , allele , biology , genetics , microsatellite , testosterone (patch) , gene , environmental health
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.