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• W3046561467 abstract "Abstract Background/Aims Dietary aflatoxin B1 (AFB1) exposure, which induces DNA damage and codon 249 mutation of the TP53 gene, is one of the major risk factors for hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection and AFB1 exert synergistic effects to promote carcinogenesis and TP53 R249S mutation in HCC. Methods A genome-wide association study (GWAS) was conducted on 485 cases of HCC with chronic HBV infection, followed by a two-stage replication study on 270 cases with chronic HBV infection. Susceptibility variants for the TP53 R249S mutation in HCC were identified based on both GWAS and replication analysis. The associations of identified variants with expression levels of their located genes were validated in 20 paired independent samples. Results Our results showed that TP53 R249S was significantly associated with ADAMTS18 rs9930984 (adjusted P = 4.84×10 −6 ), WDR49 rs75218075 (adjusted P = 7.36 × 10 −5 ) and SLC8A3 rs8022091 (adjusted P = 0.042). Additionally, ADAMTS18 mRNA expression was significantly higher in HCC tissue, compared with paired non-tumor tissue ( P = 0.041) and patients carrying the TT genotype at rs9930984 showed lower ADAMTS18 expression in non-tumor tissue, compared with those carrying the GT genotype ( P = 0.0028). Conclusions TP53 expression is significantly associated with R249S mutation in HCC. Our collective results suggest that rs9930984, rs75218075 and rs8022091 are associated with susceptibility to the R249S mutation in cases of HCC exposed to AFB1 and HBV infection." @default.
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• W3046561467 date "2020-08-03" @default.
• W3046561467 modified "2023-10-14" @default.
• W3046561467 title "Genome-wide association study of TP53 R249S mutation in hepatocellular carcinoma with aflatoxin B1 exposure and hepatitis B virus infection in Guangxi" @default.
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• W3046561467 doi "https://doi.org/10.1101/2020.08.03.235135" @default.
• W3046561467 hasPublicationYear "2020" @default.
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