Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis

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Background: Elevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians. Methods: Direct DNA sequencing was carried out to sequence AFP promoter, exons, and 3′ untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. Results: In this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3′UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis. Conclusion: Genetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians. © 2009 Elsevier B.V. All rights reserved.

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Suriapranata, I. M., Sudania, W. M., Tjong, W. Y., Suciptan, A. A., Gani, R. A., Hasan, I., … Tai, S. (2010). Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis. Clinica Chimica Acta, 411(5–6), 351–358.

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