Watling Cody Z, Petrick Jessica L, Graubard Barry I, Zhang Xuehong, Barnett Matthew J, Buring Julie E, Chen Yu, Eliassen A Heather, Gaziano J Michael, Hofmann Jonathan N, Huang Wen-Yi, Kang Jae H, Koshiol Jill, Loftfield Erikka, Lee I-Min, Moore Steven C, Mucci Lorelei A, Neuhouser Marian L, Newton Christina C, Palmer Julie R, Purdue Mark P, Rosenberg Lynn, Sesso Howard D, Shrubsole Martha, Tinker Lesley, Triplette Matthew, Um Caroline Y, Visvanathan Kala, Watts Eleanor L, Wactawski-Wende Jean, Willett Walter, Wu Fen, Zheng Wei, Campbell Peter T, Barupal Dinesh, McGlynn Katherine A
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States.
Slone Epidemiology Center, Boston University, Boston, MA, United States.
JNCI Cancer Spectr. 2025 Sep 1;9(5). doi: 10.1093/jncics/pkaf086.
Bile acids are produced in the liver and are important for lipid digestion. Higher-circulating bile acid levels, however, have been linked to metabolic disorders, inflammation, and gut microbiota dysbiosis, which have been implicated in liver carcinogenesis. To date, few epidemiological studies have explored the association between circulating bile acids and liver cancer risk.
We conducted a nested case-control study among 12 prospective cohort studies located in the United States. Fifteen prediagnostic circulating bile acids were measured from blood samples among 872 individuals who developed liver cancer and 872 matched control participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted conditional logistic regression analysis of circulating bile acid levels and liver cancer risk.
Primary conjugated bile acid concentrations were positively associated with higher risk of liver cancer (OR per doubling in concentrations [log2] and 95% CI of glycocholic acid: 1.32, 1.24 to 1.40; glycochenodeoxycholic acid: 1.33, 1.24 to 1.43; taurocholic acid: 1.28, 1.22 to 1.35; and taurchenodeoxycholic acid: 1.32, 1.24 to 1.39). Secondary conjugated bile acids were also positively associated with liver cancer risk (doubling of concentrations OR ranged from 1.11 to 1.22). Unconjugated bile acid concentrations were generally not associated with liver cancer risk, except lithocholic acid (OR per doubling: 1.27, 1.16 to 1.39). When analyses were separated into the 2 main subtypes of liver cancer, hepatocellular carcinoma (HCC; 438 cases/438 controls) and intrahepatic cholangiocarcinoma (ICC; 111 cases/111 controls), significant heterogeneity was observed for primary conjugated bile acid concentrations (all P < .001) that showed positive significant associations with HCC but not ICC.
These results suggest that bile acids may be important markers of HCC risk and contribute to hepatocarcinogenesis; however, further research using serial measurements is needed.
胆汁酸在肝脏中产生，对脂质消化很重要。然而，循环胆汁酸水平升高与代谢紊乱、炎症及肠道微生物群失调有关，而这些都与肝癌发生有关。迄今为止，很少有流行病学研究探讨循环胆汁酸与肝癌风险之间的关联。
我们在美国的12项前瞻性队列研究中开展了一项巢式病例对照研究。对872例患肝癌个体及872例匹配的对照参与者的血样进行了15种诊断前循环胆汁酸的检测。使用多变量调整的条件逻辑回归分析循环胆汁酸水平与肝癌风险，估计比值比（OR）和95%置信区间（CI）。
原发性结合胆汁酸浓度与较高的肝癌风险呈正相关（浓度每增加一倍的OR值及95%CI：甘氨胆酸为1.32，1.24至1.40；甘氨鹅脱氧胆酸为1.33，1.24至1.43；牛磺胆酸为1.28，1.22至1.35；牛磺鹅脱氧胆酸为1.32，1.24至1.39）。继发性结合胆汁酸也与肝癌风险呈正相关（浓度增加一倍的OR值范围为1.11至1.22）。除石胆酸外，未结合胆汁酸浓度一般与肝癌风险无关（浓度每增加一倍的OR值为1.27，1.16至1.39）。当分析分为肝癌的两种主要亚型，即肝细胞癌（HCC；438例/438例对照）和肝内胆管癌（ICC；111例/111例对照）时，观察到原发性结合胆汁酸浓度存在显著异质性（所有P < .001），其与HCC呈显著正相关，但与ICC无关。
这些结果表明胆汁酸可能是HCC风险的重要标志物，并有助于肝癌发生；然而，需要使用系列测量进行进一步研究。
