Large-scale search of single nucleotide polymorphisms for hepatocellular carcinoma susceptibility genes in patients with hepatitis C.
Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC). The host genetic factors that are involved in the development of HCC in patients with HCV infection remain to be investigated. To search for single nucleotide polymorphisms (SNPs) in HCC susceptibility genes, 393 SNPs in 171 candidate genes were examined in 188 Japanese patients with chronic HCV infection, including 77 patients with HCC. HCC-related SNPs were then examined in another 188 patients (including 93 patients with HCC) with chronic HCV infection. Haplotype analyses of HCC-related genes were performed in a total of 376 patients. Of the 393 SNPs, 31 SNPs in 29 genes were significantly associated with HCC based on an initial screening (P < .05). Of these 31 SNPs, 3 SNPs of 3 genes (SCYB14, GFRA1, and CRHR2) were significantly associated with HCC in a secondary screening. Haplotype analyses of these 3 genes identified 2 haplotype blocks associated with HCC. In conclusion, these SNPs and haplotypes located in the SCBY14, CRHR2, and GFRA1 genes will be used as markers to identify a subgroup of Japanese patients with chronic HCV infection who are at high risk of developing HCC.
Kato
Naoya
N
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. kato-2im@h.u-tokyo.ac.jp
Ji
Guijin
G
Wang
Yue
Y
Baba
Masanori
M
Hoshida
Yujin
Y
Otsuka
Motoyuki
M
Taniguchi
Hiroyoshi
H
Moriyama
Masaru
M
Dharel
Narayan
N
Goto
Tadashi
T
Shao
Run-Xuan
RX
Matsuura
Tadashi
T
Ishii
Keisuke
K
Shiina
Shuichiro
S
Kawabe
Takao
T
Muramatsu
Masaaki
M
Omata
Masao
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D012307:Risk Factors
C101531:CRF receptor type 2; C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases