Pre-diagnostic circulating bile acid concentrations and liver cancer risk: a nested case-control analysis of 12 cohorts.
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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
Аннотация
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.