Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women.
Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women.
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DOI：
10.1136/gutjnl-2011-300719
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发表时间：
2012-09
期刊：
影响因子：
24.5
通讯作者：
Limburg PJ
中科院分区：
文献类型：
--
作者：
Limsui D;Vierkant RA;Tillmans LS;Wang AH;Weisenberger DJ;Laird PW;Lynch CF;Anderson KE;French AJ;Haile RW;Harnack LJ;Potter JD;Slager SL;Smyrk TC;Thibodeau SN;Cerhan JR;Limburg PJ
绝经后激素（PMH）治疗可能会降低结直肠癌（CRC）的风险，但现有的数据是不确定的。在基于人群的爱荷华州老年妇女健康研究中，评估PMH治疗与CRC事件之间的总体和分子定义亚型的相关性。从爱荷华州妇女健康研究参与者（55-69岁）中收集基线（1986年）暴露数据。收集并分析了553例CRC病例的存档石蜡包埋组织标本，以确定微卫星不稳定性（MSI-L/MSS或MSI-H），CpG岛甲基化表型（CIMP阴性或CIMP阳性）和BRAF突变（BRAF野生型或BRAF突变）状态。拟合多变量考克斯回归模型以估计RR和95% CI。PMH疗法（曾经使用与从未使用）与总体CRC事件呈负相关（RR=0.82; 95% CI 0.72 - 0.93），MSI-L/MSS肿瘤的风险显著降低（RR=0.75; 95% CI 0.60 - 0.94），CIMP阴性的临界风险显著降低（RR=0.79; 95% CI 0.63至1.01）和BRAF-野生型（RR=0.83; 95% CI 0.66至1.04）肿瘤。对于PMH治疗>5年，MSI-L/MSS、CIMP阴性和BRAF野生型肿瘤的亚型特异性风险估计分别为：RR=0.60，95%CI 0.40至0.91; RR=0.68，95%CI 0.45至1.03; RR=0.70，95%CI 0.47至1.05。PMH治疗与MSI-H、CIMP阳性或BRAF突变的CRC亚型无显著相关性。在这项前瞻性队列研究中，PMH治疗与不同的分子定义的CRC亚型呈负相关，这可能与雌激素和/或孕激素对结直肠癌发生的异质性途径的不同作用有关。
Postmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive. 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. 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. 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. 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.
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影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
5
作者：
FOLSOM, AR;KAYE, SA;WALLACE, RB
通讯作者：
WALLACE, RB
DOI：
10.1158/1055-9965.epi-08-1209
发表时间：
2009-05
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Prentice RL;Pettinger M;Beresford SA;Wactawski-Wende J;Hubbell FA;Stefanick ML;Chlebowski RT
通讯作者：
Chlebowski RT
影响因子：
120.7
作者：
LaCroix, Andrea Z.;Chlebowski, Rowan T.;Manson, JoAnn E.;Aragaki, Aaron K.;Johnson, Karen C.;Martin, Lisa;Margolis, Karen L.;Stefanick, Marcia L.;Brzyski, Robert;Curb, J. David;Howard, Barbara V.;Lewis, Cora E.;Wactawski-Wende, Jean
通讯作者：
Wactawski-Wende, Jean
影响因子：
29.4
作者：
Leggett, Barbara;Whitehall, Vicki
通讯作者：
Whitehall, Vicki