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Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways.

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.

Authors+Show Affiliations

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany.Institute of Pathology, University Medical Center Mainz, Mainz, Germany. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. NCT Tissue Bank, National Center for Tumor Diseases (NCT), Heidelberg, Germany.Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Germany.Institute of Pathology, Charité University Medicine, Berlin, Germany.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31943160

Citation

Amitay, Efrat L., et al. "Postmenopausal Hormone Replacement Therapy and Colorectal Cancer Risk By Molecular Subtypes and Pathways." International Journal of Cancer, 2020.
Amitay EL, Carr PR, Jansen L, et al. Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways. Int J Cancer. 2020.
Amitay, E. L., Carr, P. R., Jansen, L., Alwers, E., Roth, W., Herpel, E., ... Hoffmeister, M. (2020). Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways. International Journal of Cancer, doi:10.1002/ijc.32868.
Amitay EL, et al. Postmenopausal Hormone Replacement Therapy and Colorectal Cancer Risk By Molecular Subtypes and Pathways. Int J Cancer. 2020 Jan 14; PubMed PMID: 31943160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways. AU - Amitay,Efrat L, AU - Carr,Prudence R, AU - Jansen,Lina, AU - Alwers,Elizabeth, AU - Roth,Wilfried, AU - Herpel,Esther, AU - Kloor,Matthias, AU - Bläker,Hendrik, AU - Chang-Claude,Jenny, AU - Brenner,Hermann, AU - Hoffmeister,Michael, Y1 - 2020/01/14/ PY - 2019/09/10/received PY - 2019/12/17/revised PY - 2019/12/18/accepted PY - 2020/1/17/pubmed PY - 2020/1/17/medline PY - 2020/1/17/entrez KW - colorectal neoplasms KW - hormone replacement therapy KW - molecular epidemiology KW - sessile serrated JF - International journal of cancer JO - Int. J. Cancer N2 - 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. SN - 1097-0215 UR - https://www.unboundmedicine.com/medline/citation/31943160/Postmenopausal_hormone_replacement_therapy_and_colorectal_cancer_risk_by_molecular_subtypes_and_pathways L2 - https://doi.org/10.1002/ijc.32868 DB - PRIME DP - Unbound Medicine ER -