rs2275959

This case-control study of 1,745 Southern Chinese subjects (643 HBV-related HCC patients, 549 CHB carriers, 553 HBV natural clearance subjects) identified 8 potentially functional lncRNA SNPs from two lncRNAs (lnc-ACACA-1 and lnc-RP11-150O12.3) located in HBV-related HCC GWAS susceptibility regions. The study found that rs9908998 in lnc-ACACA-1 significantly increased lymphatic metastasis risk (Adjusted OR = 1.95, 95% CI = 1.20-3.17), and that rs2275959, rs1008547, and rs11776545 in lnc-RP11-150O12.3 showed significant multiplicative and additive interactions with cancer family history on HBV-related HCC susceptibility, as well as associations with distant metastasis (Adjusted OR = 1.45, 95% CI = 1.06-1.97 for rs2275959; OR = 1.45, 95% CI = 1.06-1.98 for rs1008547; OR = 1.40, 95% CI = 1.03-1.91 for rs11776545).

This association study of 6039 European subjects (1020 HCC cases, 5019 controls including prospective cohorts) identified PNPLA3 rs738409 (OR=3.91, p=1.14E-09) and TM6SF2 rs58542926 (OR=1.79, p=0.001) as significant risk variants for hepatocellular carcinoma in alcoholic liver disease patients, with a dose-dependent additive effect. PNPLA3 rs738409 was also associated with HCC developed on non-fibrotic liver (OR=2.19, p=0.007), suggesting a direct carcinogenic role independent of cirrhosis.