Single nucleotide polymorphisms of XRCC3 gene in hepatocellular carcinoma – relationship with clinicopathological features

Abstract

Recent studies support the involvement of XRCC3 gene polymorphisms in carcinogenesis. Our study focuses on the identification of polymorphic variants of XRCC3 in hepatocellular carcinoma (HCC) and an analysis of the relationship between these polymorphic variants and clinicopathological (including the genotype specific risk) and survival characteristics. Fifty cases of HCC were genotyped using molecular biology techniques for Thr241Met, rs861539 (c.722C>T) and 5'-UTR, rs1799796 (c.562-14A>G) polymorphisms. Statistical analysis was based on χ2, Fisher's, logistic regression (odd ratio -OR), and log-rank tests. Statistically significant differences were shown only for rs1799796 A>G and tumour grade, between wild type (AA) and heterozygote (AG) genotypes, and wild type (AA) and heterozygote & homozygote (AG & GG) genotypes. The logistic regression analysis found an OR of rs1799796 polymorphism occurrence in HCC related to tumour grade. The statistical analysis revealed, for the rs861539 C>T polymorphism, a better survival only for the homozygote genotype (TT) compared to the heterozygote (CT), and for rs1799796 A>G polymorphism, a longer survival for the wild type (AA) compared to heterozygote (AG) and to heterozygote & homozygote (AG & GG) genotypes, respectively. Our results suggest that XRCC3 gene SNPs could influence the tumour aggressiveness expressed by tumour grade.

Evaluation of X-Ray Repair Cross-Complementing Family Members as Potential Biomarkers for Predicting Progression and Prognosis in Hepatocellular Carcinoma

“…Similar to XRCC1 and XRCC2, XRCC3 has been researched widely in the correlation between gene polymorphisms and the risk of cancer. Several studies have revealed multiple gene mutations, including rs861539 C > T, rs1799796 A > G, C241T, which are significantly associated with enhanced risk of HCC [38,39]. Besides, XRCC3 overexpression has been found to be associated with clinical factors in breast cancer [40].…”

Cellular Responses to Aflatoxin-Associated DNA Adducts

“…XRCC3 (X-ray complementing defective repair in Chinese hamster cells) encodes a Rad51 paralog which is involved in double-strand break repair and could be involved in error-free by pass of AFB1associated DNA lesions. The XRCC3 rs861539 allele (codon Thr241Met polymorphism) is a risk factor for HCC, and the risk is aggravated if individuals are exposed to AFB1 [62][63][64]. Other alleles that have been associated with higher risk for HCC include those participating in the base excision repair (BER) and NER pathways, such as XRCC1 rs25487 polymorphism (codon Arg399Gln polymorphism) [65,66] and XPD rs25487 polymorphism, respectively [67].…”

“…It has not yet been determined whether mammalian cells defective in homologous recombination exhibit more AFB1associated mutations. Nonetheless, it is interesting that polymorphisms of XRCC3 [62][63][64], which functions in homologous recombination, are a risk factor for HCC.…”

Hepatocellular carcinoma – clinicopathological characteristics, survival, and expression of various histologic molecular markers

“…A large number of genetic alterations and molecular factors have been shown to associate with the progression of HCC, and they have potential prognostic significance [6,14]. Understanding the molecular pathways in liver carcinogenesis and identification of molecules as targets for therapeutic intervention give hope for better prognosis of patients with HCC [11].…”

“…Besides the fundamental role β-catenin has regulating the E-cadherin-catenin cell adhesion complex, β-catenin also acts as a transcriptional activator of the Wnt signalling pathway and regulates transcription of target genes responsible for cell proliferation and differentiation [19][20][21]. Many authors have studied the genetic alteration of E-cadherin and β-catenin, their related pathways, and expression of E-cadherin and β-catenin molecules in various cancers including HCC [5,14,22,23]. Reduced E-cadherin expression is associated with the progression of HCC, poor prognosis, poor differentiation, metastasis, and TNM stage [17,21,24,25,26].…”