Associations between Environmental Exposures and Incident Colorectal Cancer by ESR2 Protein Expression Level in a Population-Based Cohort of Older Women.
Associations between Environmental Exposures and Incident Colorectal Cancer by ESR2 Protein Expression Level in a Population-Based Cohort of Older Women.
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根据老年女性群体中 ESR2 蛋白表达水平的环境暴露与结直肠癌发病之间的关联。
DOI：
10.1158/1055-9965.epi-14-0756
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Li
中科院分区：
文献类型：
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作者：
Tillmans,LoriS;Vierkant,RobertA;Wang,AliceH;Samadder,NiloyJewel;Lynch,CharlesF;Anderson,KristinE;French,AmyJ;Haile,RobertW;Harnack,LisaJ;Potter,JohnD;Slager,SusanL;Smyrk,ThomasC;Thibodeau,StephenN;Cerhan,JamesR;Li
背景：吸烟（吸烟）、激素治疗（MHT）和叶酸摄入（叶酸）均被认为影响结直肠癌的风险，但其潜在的分子机制仍不完全明确。雌激素受体β（ESR 2）的表达已与结直肠癌分期和survival.Methods：在这项前瞻性队列研究中，我们研究了吸烟，MHT，叶酸相关的结直肠癌风险ESR 2蛋白表达水平之间的参与者在爱荷华州妇女健康研究（IWHS）。在基线时评估自我报告的暴露变量。收集存档的石蜡包埋的结直肠癌组织标本，并通过IHC评价ESR 2蛋白表达。多变量考克斯回归模型拟合估计吸烟，MHT，或叶酸和ESR 2定义的结直肠癌subtypes.Results之间的关联的相对危险度（RR）和95%置信区间（CI）：信息环境暴露和蛋白质表达数据可用于491例事件结直肠癌病例。观察到ESR 2-低和-高肿瘤与几个吸烟相关变量之间存在正相关性，最显著的是每天平均吸烟数量（与不吸烟者相比，吸烟≥40支的ESR 2-低RR，4.24; 95%CI，1.81-9.91; ESR 2-高RR，2.15; 95%CI，1.05-4.41）。对于MHT，观察到暴露持续时间较长与ESR 2低肿瘤的统计学显著相关性（RR，0.54; 95%CI，0.26-1.13，>5年，与从未使用相比）。结论：在这项研究中，吸烟和MHT与ESR 2表达模式相关。影响：这些数据支持吸烟和MHT对老年妇女结直肠癌发生的ERβ相关途径的可能异质性影响。癌症流行病学生物标志物Prev; 24（4）; 713-9。©2015 AACR.
Background:Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival.Methods:In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes.Results:Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and -high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81–9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05–4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26–1.13 for >5 years compared with never use). No associations were found for folate.Conclusions:In this study, smoking and MHT were associated with ESR2 expression patterns.Impact:These data support possible heterogeneous effects from smoking and MHT on ERβ-related pathways of colorectal carcinogenesis in older women.Cancer Epidemiol Biomarkers Prev; 24(4); 713–9. ©2015 AACR.