UCLA

Background: Liver cancer is a major public health burden in China. Polymorphisms in genes from stem cell pathway and microRNA related genes have been associated with liver cancer in experimental studies. However, few well-designed large population-based studies have been conducted to evaluate the impact of genetic susceptibility and established environmental risk factors including hepatitis virus infections, alcohol consumption, tobacco smoking and exposure to aflatoxin and their interaction on the carcinogenesis. Methods: A population-based case-control study was conducted in Jiangsu from 2003 to 2010. A total of 2,011 new cases and 7,933 randomly selected healthy controls were consented and interviewed. 58 SNPs and serum HBV/HCV infection markers were measured. Unconditional logistic regression models were used in determining the odds ratios. Results: HBsAg positive was confirmed as a strong risk factor for liver cancer with an aOR of 9.85 (95% CI: 8.28-11.72). Alcohol consumption (aOR: 1.91, 95% CI: 1.61-2.28), tobacco smoking (aOR: 1.48, 95% CI: 1.25-1.75), family history of liver cancer (aOR: 4.19, 95% CI: 3.17-5.53) and history of raw water drinking (aOR: 1.32, 95% CI: 1.13-1.55) also showed positive associations. Positive statistical interactions were observed among them. Rs896849 (TP53INP1 gene, C/C vs. T/T, aOR: 0.27, 95% CI: 0.08-0.87), rs11614913 (miR-196a2 gene, C/C vs. T/T, aOR: 0.44, 95% CI: 0.27-0.71), rs4730775 (WNT2 gene, C/T vs. C/C, aOR: 0.71, 95% CI: 0.50-0.99) and rs2241802 (FZD3 gene, A/A vs. G/G, aOR: 0.58, 95% CI: 0.37-0.91) showed inverse associations with liver cancer. Statistical interactions were detected between rs896849, rs11614813 and environmental exposures. Among HBsAg positive participants, rs12828 (WWOX gene), rs2740348 (Gemin4 gene), rs222851 (DVL2 gene) and rs3734637 (HEY2 gene) showed associations with serum HBV viral load level. Conclusion: HBV infection, alcohol consumption, tobacco smoking and family history of liver cancer showed joint effect on liver cancer in this Chinese population. Some SNPs from microRNA related genes and stem cell pathway genes showed association with liver cancer and interacted with environmental exposures. Elimination of infection and intervention on risk behaviors are important in Chinese population. The detected SNPs may serve as new markers for cancer prevention and therapy targets once the associations are further confirmed.