3. X-ray repair cross complementing group 3 polymorphism in association with aflatoxin B1 exposure in chronic hepatitis (B & C) and hepatocellular carcinoma

Abstract

Background and Aims: X-ray repair cross-complementing group 3 (XRCC3) is a constituent of DNA repair genes involved in the process of DNA double-strand breaks repair pathway. XRCC3 Thr241Met (C > T) polymorphism is a single nucleotide polymorphism (SNP) at codon 241 in exon 7. We aimed to study polymorphisms of XRCC3 Thr241Met in Chronic Hepatitis (B & C) and Hepatocellular carcinoma patients and healthy individuals. This was correlated with total aflatoxin content in various indigenous foods consumed by general population and chronic liver disease patients from Assam, India. Methods: We conducted a hospital based case control study including 70 Chronic Hepatitis (B & C) cases and 70 healthy controls, alongwith 20 Hepatocellular Carcinoma cases and 20 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) assay in Assamese population. Results: Out of 70 cases of chronic liver disease (HBV & HCV) 67.14% patients showed SNP for XRCC3 Thr241Met out of which 32.85% were homozygous (C/C), 50% were heterozygous (C/T) and 17.14% were mutated (T/T). Whereas out of 20 Hepatocellular carcinoma cases 30% were homozygous (C/C), 35% were heterozygous (C/T) and 35% were mutated (T/T). No significant association of SNP's was observed with duration of alcohol consumption, raised transaminase, low platelet count, HBsAg and Anti HCV status. The indigenous food samples were examined by HPLC technique which did not reveal significant aflatoxin content. Conclusions: The XRCC3 codon 241 polymorphism displayed a relationship with HCC and in chronic hepatitis B & C. Codon 241 mutation was significantly increased in patients of HCC and in chronic HBV or HCV. There is increased risk for the individuals with XRCC3 CT genotype [OR = 2.43 (1.17–5.03), p = 0.01*] and TT genotype [OR = 4.17 (1.30–13.34), p = 0.01*]. Hence, presence of mutation in the codon of XRCC3 TT genotype in patients of chronic HBV and HCV could indicate the likelihood of progression to HCC. The authors have none to declare.