绝经后激素治疗与按分子定义亚型和肿瘤位置划分的结直肠癌风险
Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.
作者信息
Labadie Julia D, Harrison Tabitha A, Banbury Barbara, Amtay Efrat L, Bernd Sonja, Brenner Hermann, Buchanan Daniel D, Campbell Peter T, Cao Yin, Chan Andrew T, Chang-Claude Jenny, English Dallas, Figueiredo Jane C, Gallinger Steven J, Giles Graham G, Gunter Marc J, Hoffmeister Michael, Hsu Li, Jenkins Mark A, Lin Yi, Milne Roger L, Moreno Victor, Murphy Neil, Ogino Shuji, Phipps Amanda I, Sakoda Lori C, Slattery Martha L, Southey Melissa C, Sun Wei, Thibodeau Stephen N, Van Guelpen Bethany, Zaidi Syed H, Peters Ulrike, Newcomb Polly A
机构信息
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
出版信息
JNCI Cancer Spectr. 2020 May 19;4(5):pkaa042. doi: 10.1093/jncics/pkaa042. eCollection 2020 Aug.
BACKGROUND
Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location.
METHODS
We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, and mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided.
RESULTS
Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and or status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; =.01) tumors.
CONCLUSIONS
We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
背景
绝经后激素治疗（HT）与结直肠癌（CRC）风险降低相关。由于CRC是一种异质性疾病，我们评估了HT与CRC之间的关联在病因学相关、分子定义的肿瘤亚型和肿瘤位置方面是否存在差异。
方法
我们汇总了来自8项观察性研究的8220名绝经后女性（3898例CRC病例和4322例对照）的肿瘤亚型（微卫星不稳定性状态、CpG岛甲基化表型状态以及突变、途径：腺瘤-癌、替代、锯齿状）、肿瘤位置（近端结肠、远端结肠、直肠）和HT使用情况的数据。我们使用多项逻辑回归来估计曾经使用HT与从未使用HT相比，每种肿瘤亚型与对照之间关联的优势比（OR）和95%置信区间（CI）。模型针对研究、年龄、体重指数、吸烟状况和CRC家族史进行了调整。所有统计检验均为双侧检验。
结果
在绝经后女性中，曾经使用HT与总体CRC风险降低38%相关（OR = 0.62，95%CI = 0.56至0.69）。根据微卫星不稳定性、CpG岛甲基化表型和或状态，这种关联相似。然而，与腺瘤-癌途径（OR = 0.63，95%CI = 0.55至0.73；P =.04）和替代途径（OR = 0.61，95%CI = 0.51至0.72）相比，通过锯齿状途径发生的肿瘤的关联减弱（OR = 0.81，95%CI = 0.66至1.01）。此外，与直肠肿瘤（OR = 0.54，95%CI = 0.46至0.63）和远端结肠肿瘤（OR = 0.57，95%CI = 0.49至0.66；P =.01）相比，近端结肠肿瘤的关联较弱（OR = 0.71，95%CI = 0.62至0.80）。
结论
我们观察到HT使用与总体CRC风险之间存在强烈的负相关，这可能主要反映了HT使用对通过腺瘤-癌和替代途径以及远端结肠和直肠肿瘤发生的肿瘤的益处。
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