估计6-20%的所有胆总管癌（CCA）的诊断可以用原发性硬化性胆管炎（PSC）来解释，但在没有PSC的情况下，潜在的风险因素尚不清楚。我们在美国研究了不同风险因素与肝内胆管癌（ICC）和肝外胆管癌（ECC）的关联。我们在MD Anderson癌症中心进行了一项病例对照研究，研究对象包括121例ECC患者和308例ICC患者，与1061名健康对照组进行比较。采用多变量 logistic 回归分析估计每个风险因素的调整后的比值比（AOR）和95%的置信区间。亚洲人、糖尿病、癌症家族史和胆囊结石与患ICC和ECC的概率相关。在青少年早期（20-40岁）的每1单位的身体质量指数的增加与CCA的诊断年龄的降低有关（6.7个月，P<0.001；ICC为6.1个月，P=0.001；ECC为8.2个月，P=0.007）。癌症家族史与ICC和ECC发展的风险显著相关；ICC和ECC的AOR（95%置信区间）分别为1.11（1.06-1.48）和1.32（1.01-2.00）。在本研究中，青少年早期肥胖的发病与CCA显著相关，并可能预示着较正常体重个体更早被诊断出。该研究突出了肥胖与CCA的关联，且独立于PSC。有必要考虑在没有脂肪肝和肝硬化的情况下，肥胖的机制途径。

It is estimated that 6-20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the US.We conducted a case-control study of 121 ECC patients and 308 ICC patients treated at MD Anderson Cancer Center between May 2014 and March 2020, compared to 1061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted odds ratio (AOR) and 95% confidence interval for each risk factor.Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P<0.001; 6.1 months for ICC, P=0.001; 8.2 months for ECC, P=0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95%CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively.In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals.The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.