女性生殖因素与胆道癌的关系：来自胆道癌汇集项目的研究。
Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.
机构信息
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
出版信息
J Hepatol. 2020 Oct;73(4):863-872. doi: 10.1016/j.jhep.2020.04.046. Epub 2020 May 11.
BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.
METHODS
We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.
RESULTS
During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.
CONCLUSION
We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.
LAY SUMMARY
Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
背景与目的
胆囊癌（GBC）以女性高发为特征，而其他胆道癌（BTC）则以男性高发为特征。然而，女性生殖因素在 BTC 发病机制中的作用仍不清楚。
方法
我们汇集了 19 项研究的数据，这些研究涉及 150 多万名参与胆道癌汇集项目的女性，以研究生育次数、初潮年龄、生育年限和绝经年龄与 BTC 的关系。分别分析了亚洲和非亚洲女性的初潮年龄和生育年限与 BTC 的关系。使用 Cox 比例风险模型估计风险比（HR）和 95%置信区间（CI），按研究分层。
结果
在 21681798 人年的随访期间，发生 875 例胆囊癌、379 例肝内胆管癌（IHBDC）、450 例肝外胆管癌（EHBDC）和 261 例壶腹癌（AVC）。高生育次数与胆囊癌风险相关（≥5 次 vs. 0 次生育 1.72；95%CI 1.25-2.38）。初潮年龄（每年增加 1.15；95%CI 1.06-1.24）与亚洲女性的胆囊癌风险相关，而生育年限与非亚洲女性的胆囊癌风险相关（每增加 5 年 1.13；95%CI 1.04-1.22）。亚洲女性中，较晚的初潮年龄与 IHBDC（HR 1.19；95%CI 1.09-1.31）和 EHBDC（HR 1.11；95%CI 1.01-1.22）相关，而亚洲女性中，较晚的初潮年龄与 IHBDC（HR 1.19；95%CI 1.09-1.31）和 EHBDC（HR 1.11；95%CI 1.01-1.22）相关。
结论
我们观察到生育次数增加与胆囊癌风险增加相关。在亚洲女性中，初潮年龄较大与胆囊癌、肝内胆管癌和肝外胆管癌风险增加相关，而在非亚洲女性中，生育年限增加与胆囊癌风险相关。这些结果表明，性激素对胆道癌的影响具有地域差异。
简要说明
我们的研究结果表明，生育次数较多的女性（尤其是生育 5 次或以上的女性）患胆囊癌的风险增加。在来自亚洲国家的女性中，初潮年龄较晚会增加胆囊癌、肝内胆管癌和肝外胆管癌的风险。我们在来自西方国家的女性中没有看到这种关联。绝经年龄与任何胆道癌的风险均无关联。
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