An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma.

作者: Akira Sakurada , Koji Miyanishi , Shingo Tanaka , Masanori Sato , Hiroki Sakamoto

DOI: 10.1016/J.FREERADBIOMED.2018.09.010

关键词: MUTYHBiologyDNA repairSingle-nucleotide polymorphismCancer researchBase excision repairGenotypePromoterHepatocellular carcinomaAllele

摘要: Abstract Background & aims The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants these and the risk developing hepatocellular carcinoma (HCC). Methods Nineteen tagging SNPs (including MUTYH, OGG1 MTH1) were genotyped using iPLEX assays; one significant SNP was found confirmed Japanese patients with chronic hepatitis C (CHC) (n = 38 HCC 55 controls). effects modifying intronic determined by luciferase assays. MUTYH-null mice used to examine involvement oxidative stress DNA enzymes hepatocarcinogenesis. Results Significant associations for a single intron (rs3219487) MUTYH gene. A/A or G/A genotypes higher than those G/G genotype (OR = 9.27, 95% CI = 2.39 −32.1, P = 0.0005). mRNA levels both peripheral mononuclear cells significantly lower subjects (P = 0.0157 0.0108, respectively). We that −2000 promoter region is involved enhanced expression insertion major allele sequence rs3219487. Liver tumors observed after 12 months´ high iron diet, but no developed when dietary anti-oxidant (N-Acetyl- L -cysteine) also provided. Conclusions CHC rs3219487 adenine had increased HCC. iron-associated susceptible development liver unless prevented anti-oxidants.

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