Abstract 321: Aberrant methylation of multiple tumor suppressor genes and clinicopathological parameters as predictors for genotype-4 hepatitis C virus-associated hepatocellular carcinoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.321-321
• Main Authors: Zekri, Abdel-Rahman N., Bahnassy, Abeer A., Shoeab, Fatma Elzahraa M., Abdel-Aziz, Asherf O., Ali, Fahmey T., Sabry, Gilane M., Dasgupta, Nairajana, Daoud, Sayed S.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-321

Hepatocellular carcinoma (HCC) is one of the few tumors in which the incidence is on the rise worldwide. The increasing incidence of HCC is associated with the rise in hepatitis C virus (HCV) infection. It is estimated that 2.0% of the US general population are infected with HCV. Egypt has the highest prevalence of HCV/genotype 4 infection in the world, with 14% of the population infected. Little is known about the role(s) of epigenetic changes that may participate in HCV-induced HCC? Epigenetic studies directed at mapping the etiology of HCV disease progression to HCC and how they correlate with patients clinicopathological parameters are expected to provide new insights that will aid in the design of effective strategies for earlier detection and management of the disease, and therefore of great public/global health interest. The aim of the current study was to investigate the aberrant methylation of 11 genes in liver tissue samples obtained from Egyptian patients infected with HCV/genotype 4, and to explore possible relationships between aberrant methylation and clinicopathological features in HCC. Thirty-eight HCC and matching non-tumor tissues, thirty-one chronic hepatitis liver tissues, and thirteen normal liver tissues were analyzed for the methylation status of APC, FHIT, p15, p73, p14, p16, DAPK1, CDH1, RARβ, RASSF1A and O6MGMT genes by quantitative methylation-specific PCR. Based on methylation profiles using McNemar's test for paired binary data, a methylation of only 7 genes was found to be highly significant, which is dependent on disease state. For chronic hepatitis tissues, promoter methylation of p14 was highly significant in both liver tissues and peripheral blood leukocytes (PBL) (P < 0.0047 and