Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study

作者：Lishuai Qu, Fei Jin, Yan-Mei Guo, Taotao Liu, Ruyi Xue, Xiaowu Huang, Min Xu, Taoyang Chen, ZHENG-PING NI, Xizhong Shen · 发表于：Oncology Letters · 年份：2015 · DOI：10.3892/ol.2015.3958 · 被引用次数：24 · 研究领域：Cancer-related gene regulation、Hepatitis C virus research、Genetic Associations and Epidemiology

Previous studies have indicated that complex interactions among viral, environmental and genetic factors lead to hepatocellular carcinoma (HCC). To identify susceptibility alleles for hepatitis B virus (HBV)‑related HCC, the present study conducted a pilot two‑phase genome‑wide association study (GWAS) in 660 Han Chinese individuals. In phase 1, a total of 500,447 single‑nucleotide polymorphisms (SNPs) were genotyped in 50 HCC cases and 50 controls using Affymetrix GeneChip 500k Array Set. In phase 2, 1,152 SNPs were selected from phase 1 and genotyped in 282 cases and 278 controls using the Illumina GoldenGate platform. The prior probability of HCC in control subjects was assigned at 0.01, and false‑positive report probability (FPRP) was utilized to evaluate the statistical significance. In phase 1, one SNP (rs2212522) showed a significant association with HCC (Pallele=5.23x10‑8; ORallele=4.96; 95% CI, 2.72‑9.03). In phase 2, among 27 SNPs with unadjusted Pallele<0.05, 9 SNPs were associated with HCC based on FPRP criteria (FPRP <0.20). The strongest statistical evidence for an association signal was with rs2120243 (combined ORallele=1.76; 95% CI, 1.39‑2.22; P=2.00x10‑6), which maps within the fourth intron of VEPH1. The second strongest statistical evidence for an association was identified for rs1350171 (combined ORallele=1.66; 95% CI, 1.33‑2.07; P=6.48x10‑6), which maps to the region downstream of the FZD4 gene. The other potential susceptibility genes included PCDH9, PRM...