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Background: Studies in experimental animals suggest that low folate levels may play a role in liver damage and hepatocarcinogenesis. To examine this association in humans, folate levels in blood and risk for subsequent liver damage and hepatocellular carcinoma (HCC) were assessed in a population at high risk of liver cancer in China. Methods: Four hundred fifteen hepatitis B surface antigen–positive participants of the Haimen City Cohort were prospectively followed between 1998 and 2002. Serum and RBC folate levels were determined at baseline. Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured semiannually. Logistic regression modeling was used to examine the presence of hepatitis B virus DNA and HCC, whereas linear regression with a log-link function was used to examine ALT levels. Results: There was a statistically significant inverse association between serum folate level and ALT level. ALT levels decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86; 95% confidence interval, 0.76-0.97 for the highest compared with the lowest quartile; Ptrend = 0.002). After exclusion of three persons with prevalent HCC, 20 (4.9%) of the 412 study participants developed HCC during follow-up, with a median time between enrollment and HCC diagnosis of 2.66 years (interquartile range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to persons in all other quartiles, the analysis found that higher RBC folate levels were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95% confidence interval, 0.13-0.86; Ptrend = 0.02). Conclusions: This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and HCC. (Cancer Epidemiol Biomarkers Prev 2007;6(6):1279–82)

Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common histologic types of primary liver cancer. Incidence rates of both HCC and ICC are increasing in the United States. Metabolic syndrome, characterized by increased fasting glucose level, central adiposity, dyslipoproteinemia and hypertension, has been linked with HCC and may also modify the risk of ICC. The magnitude of the association, however, has not been investigated at the population level in the US. We therefore examined the association between metabolic syndrome and the development of both primary liver cancers in the general U.S. population. Methods: All persons aged 65 years and older diagnosed with histologically confirmed HCC and ICC between 1993 and 2005 were identified in the SEER-Medicare linked database. The cases were compared to a 5% sample of individuals residing in the same geographic regions of the SEER registries as the cases. The prevalences of metabolic syndrome and other risk factors for HCC (HBV, HCV, unspecified viral hepatitis, alcoholic liver disease, unspecified cirrhosis, biliary cirrhosis, hemochromatosis, Wilson's disease, smoking) and ICC (biliary cirrhosis, cholangitis, cholelithiasis, choledochal cysts, HBV, HCV, unspecified viral hepatitis, alcoholic liver disease, non-specified cirrhosis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, smoking) were compared among the persons who developed cancer and the persons who did not. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression. Results: A total of 3,649 HCC cases, 743 ICC cases and 195,953 persons without cancer met the study inclusion criteria. Metabolic syndrome was significantly more common among persons who developed HCC (37.1%) and ICC (29.7%) than among persons who did not (17.1%, p Conclusions: Metabolic syndrome is a risk factor for development of both HCC and ICC in the general U.S. population. Given that approximately one-third of U.S. adults have metabolic syndrome, these findings have implications for the future incidence of both HCC and ICC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 945. doi:10.1158/1538-7445.AM2011-945