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

作者：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^*

来源：Gut, 2012, 61(9): 1299-1305.

DOI：10.1136/gutjnl-2011-300719

Background Postmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive. %26lt;br%26gt;Objectives To evaluate associations between PMH therapy and incident CRC, overall and by molecularly defined subtypes, in the population-based Iowa Women%26apos;s Health Study of older women. %26lt;br%26gt;Methods Exposure data were collected from Iowa Women%26apos;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. %26lt;br%26gt;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 %26gt;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. %26lt;br%26gt;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.

• 出版日期2012-9