Details

Autor(en) / Beteiligte

• Limsui, David
• Vierkant, Robert A
• Tillmans, Lori S
• Wang, Alice H
• Weisenberger, Daniel J
• Laird, Peter W
• Lynch, Charles F
• Anderson, Kristin E
• French, Amy J
• Haile, Robert W
• Harnack, Lisa J
• Potter, John D
• Slager, Susan L
• Smyrk, Thomas C
• Thibodeau, Stephen N
• Cerhan, James R
• Limburg, Paul J

Titel

Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women

Ist Teil von

• Gut, 2012-09, Vol.61 (9), p.1299-1305

Ort / Verlag

London: BMJ Publishing Group Ltd and British Society of Gastroenterology

Erscheinungsjahr

2012

Link zum Volltext

Quelle

BMJ Journals Archiv - DFG Nationallizenzen

Beschreibungen/Notizen

• BackgroundPostmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive.ObjectivesTo evaluate associations between PMH therapy and incident CRC, overall and by molecularly defined subtypes, in the population-based Iowa Women's Health Study of older women.MethodsExposure data were collected from Iowa Women's Health Study participants (55–69 years) at baseline (1986). Archived, paraffin-embedded tissue specimens for 553 CRC cases were collected and analysed to determine microsatellite instability (MSI-L/MSS or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive) and BRAF mutation (BRAF-wildtype or BRAF-mutated) status. Multivariable Cox regression models were fit to estimate RRs and 95% CIs.ResultsPMH therapy (ever vs never use) was inversely associated with incident CRC overall (RR=0.82; 95% CI 0.72 to 0.93), with a significantly lower risk for MSI-L/MSS tumours (RR=0.75; 95% CI 0.60 to 0.94), and borderline significantly lower risks for CIMP-negative (RR=0.79; 95% CI 0.63 to 1.01) and BRAF-wildtype (RR=0.83; 95% CI 0.66 to 1.04) tumours. For PMH therapy >5 years, the subtype-specific risk estimates for MSI-L/MSS, CIMP-negative and BRAF-wildtype tumours were: RR=0.60, 95% CI 0.40 to 0.91; RR=0.68, 95% CI 0.45 to 1.03; and RR=0.70, 95% CI 0.47 to 1.05, respectively. PMH therapy was not significantly associated with the MSI-H, CIMP-positive or BRAF-mutated CRC subtypes.ConclusionsIn this prospective cohort study, PMH therapy was inversely associated with distinct molecularly defined CRC subtypes, which may be related to differential effects from oestrogen and/or progestin on heterogeneous pathways of colorectal carcinogenesis.