| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Haruhiko The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60240305)
TATEISHI Keisuke The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20396948)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Genetic polymorphisms of UGT1A7, which detoxifies endogenous and environmental carcinogens, have been reported to be associated with HCC in German populations. In this study, we evaluated the association of this gene with the risk of HCC in Japanese HCV-infected patients. Genetic polymorphisms of UGT1A7 were investigated in 280 Japanese patients (122 with HCC) with chronic HCV infections. We designated the UGT1A7^*1 allele (a haplotype confering higher activity) as H and the ^*2, ^*3, and ^*4 alleles (haplotypes confering lower activity) as L. The proportions of UGT1A7 L/L and H/L alleles in patients with HCC (25% and 45%, respectively) were higher than those in patients without HCC (15% and 39%, respectively) with an odds ratio of 2.73 (95% CI:1.40-5.35) and 1.80 (95% CI:1.05-3.09), respectively, compared with the UGT1A7 H/H alleles. The UGT1A7 polymorphisms were associated with the presence of HCC in Japanese HCV-infected patients.
To search for SNPs in HCC susceptibility genes, 393 S
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NPs 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 (93 with HCC) with chronic HCV infection. Of the 393 SNPs, 31 SNPs in 29 genes were significantly associated with HCC based on an initial screening (P < 0.05). Of these 31 SNPs, three SNPs of three genes (SCYB14, GFRA1, and CRHR2) were significantly associated with HCC in a secondary screening. In conclusion, These SNPs 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.
A single nucleotide polymorphisms in the promoter region of MDM2 gene, SNP309, has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. However, the association of SNP309 with HCC is unknown. We evaluated the association of SNP309 with the risk of HCC development among Japanese patients with chronic HCV infection. We genotyped the SNP309 at the MDM2 promoter in 435 Japanese patients with chronic HCV infection including 187 patients with HCC, as well as 48 healthy subjects, using a fluorogenic polymerase chain reaction. Presence of SNP was also confirmed by direct sequencing of the MDM2 promoter region. The proportion of G/G genotype of the SNP309 in patients with HCC (33%) was significantly higher than that in patients without HCC (23%), with an odds ratio of 2.28 (95% confidence interval, 1.30-3.98). The MDM2 promoter SNP309 is associated with the presence of HCC in Japanese patients with chronic hepatitis C. Less
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