XRCC1 and XPD polymorphisms and their relation to the clinical course in hepatocarcinoma patients

Abstract

In this study genotyping of hepatocellular carcinoma (HCC) patients was conducted to detect polymorphisms on the X-ray repair cross-complementing 1 (XRCC1) and xeroderma pigmentosum complementary group D (XPD) genes and analyze the relationship of their presence with the clinical features of the cancer. A total of 172 patients with HCC were selected in Qilu Hospital, Shandong University, from January 2010 to September 2011. All patients underwent resection of HCC and no tumor metastases were found. Peripheral venous blood samples (3–5 ml) were collected from the patients to extract genomic DNA. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing. During the five-year follow-up, the survival of patients with various genotypes of XRCC1 and XPD genes were observed and compared. Logistic regression analysis was used to analyze the association between single nucleotide polymorphisms of XRCC1 and XPD genes and the prognosis of patients with HCC. χ2 tests showed that XRCC1-194, XRCC1-280 and XPD-312 gene polymorphisms were significantly correlated with the number, location and diameter of the tumors (p<0.05). No significant difference was found in the survival curve of patients presenting different genotypes of the XRCC1-194 locus (p>0.05). Nevertheless, a significant difference was found in the survival curve of patients with AA and GG genotypes of the XRCC1-280 locus and in the patients with AA, GA and GG genotypes of the XPD-312 locus (p<0.05). Logistic regression analysis showed that the XRCC1-194 genotype was not an independent risk factor for HCC mortality risk (p>0.05), but XRCC1-280 (OR=1.815, p<0.01) and XPD-312 (OR=1.815, p<0.01) genotypes were independent risk factors for a poor prognosis. Taken together our results point to polymorphisms in XRCC1 and XPD genes as being related to the clinical characteristics of HCC, making them suitable prognostic markers of HCC.

Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma

“…They also demonstrated that the mean methylation levels of the ADRA1A gene in HCC samples were not only associated with clinical characteristics but could also discriminate between HCC tissues and adjacent normal tissues, thus being suitable as a diagnostic marker. XRCC1 is a DNA repair gene that plays a crucial role in maintaining genomic integrity and stability and in the pathogenesis and carcinogenesis of various type of cancer ( 34 ). XRCC1 is significantly correlated with the number of tumors, tumor size, and location, and is also an independent risk factor for the poor prognosis of HCC ( 34 , 35 ).…”

“…XRCC1 is a DNA repair gene that plays a crucial role in maintaining genomic integrity and stability and in the pathogenesis and carcinogenesis of various type of cancer ( 34 ). XRCC1 is significantly correlated with the number of tumors, tumor size, and location, and is also an independent risk factor for the poor prognosis of HCC ( 34 , 35 ). TPX2 , a nuclear proliferation microtubule-associated protein, is essential for spindle formation and stabilizes spindle microtubules ( 36 ).…”

A Comprehensive Evaluation of the Association between Polymorphisms in XRCC1, ERCC2, and XRCC3 and Prognosis in Hepatocellular Carcinoma: A Meta-Analysis

“…In 2012, Jung et al [8] found that XRCC1 rs25487, ERCC5 rs2018836, ERCC5 rs3818356, and XRCC4 rs1805377 have significant effects on survival. Another study suggested that ERCC2 -312 genotypes but not XRCC1 -194 were independent risk factors for poor prognosis in HCC [9]. Han et al [10] showed that the XRCC1 Gln allele and XRCC3 T allele are related to a poor prognosis in HCC.…”

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway

“…Therefore, it is of utmost importance to better understand the molecular mechanisms responsible for the development of EScc and to explore novel therapies with which to improve the survival of patients with EScc. XPd is located on 19q13.2-q13.3 and encodes an ATP-dependent DNA helicase (25). XPD751 polymorphism has been shown to be associated with the occurrence and development of a wide range of malignancies, such as esophageal cancer, gastric cancer, and colorectal cancer (26)(27)(28).…”