Fine Mapping of Hepatocellular Carcinoma Susceptibility Gene on 4q: Preliminary Analysis
Date Issued
2005
Date
2005
Author(s)
Lin, Ci-Jyun
DOI
zh-TW
Abstract
Background and Aim: Hepatocellular carcinoma (HCC) is a complex disease involving both environmental and genetic factors. Several loss-of-heterozygosity studies have suggested the existence of a tumor suppressor gene for HBV-related HCC on chromosome 4q. Our previous linkage study in HCC multiplex families has found a significant linkage signal on 4q25. The aim of this present study was to finely map the presumed HCC-susceptibility locus on 4q by using a large-scale case-control study.
Materials and Method: A total of 989 male HBsAg-positive HCC cases and 956 age-sex matched HBsAg-positive controls were included. We analyzed 14 single nucleotide polymorphisms (SNPs) distributed throughout the 2-HLOD-drop internal (~10 cM) around the linkage peak identified by our previous study.
Result: overall, none of the 14 SNPs were associated with HCC. However, SNP2 was significantly associated with early-onset HCC diagnosed between 41-50 years of age (P=.0003) this association remained statistically significant even after adjusting multiple comparisons by use of calculating false discovery rate. Haplotype analysis revealed that haplotype SNP1-SNP2 was associated with HCC diagnosed between 41-50 years of age (P=.0006), and SNP8-SNP9 was associated with HCC diagnosed at age >60 (P=0.0009).
Conclusions: We found haplotypes SNP1-SNP2 and SNP8-SNP9 were significantly associated with HCC. Further association study with a higher density of markers, which focused on a broader chromosomal region, is warranted.
Subjects
肝癌
4q染色體
精細輿圖分析
HCC
4q
fine mapping
Type
thesis
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