Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women. Issue 9 (24th October 2011)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Gut. Volume 61:Issue 9(2012)
• Page Start: 1299
• Page End: 1305
• Publication Date: 2011-10-24
• Subjects: Postmenopausal hormone therapy -- colorectal cancer -- cohort study -- molecular epidemiology -- microsatellite instability -- CpG island methylator phenotype -- BRAF -- KRAS -- cancer epidemiology -- cancer genetics -- epidemiology -- statistics -- epidemiology -- gastrointestinal neoplasia -- pancreatic cancer -- epidemiology -- cancer prevention -- cancer epidemiology -- chemoprevention -- Helicobacter pylori -- acid-related diseases -- non-ulcer dyspepsia -- genetic polymorphisms -- gastric neoplasia; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2011-300719
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background: Postmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive. Objectives: To 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. Methods: Exposure 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. Results: PMH 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. Conclusions: In 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.