Polymorphisms in GSTM1 and XPD genes predict clinical outcome in advanced oral cancer patients treated with postoperative radiotherapy

Abstract

Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Ser326Cys, rs1052133), XRCC1 (Arg194Trp, rs1799782, and Arg399Gln, rs25487), XPD (Asp312Asn, rs1799793, and Lys751Gln, rs13181) can predict clinical outcome in 187 oral squamous cell carcinoma patients treated with postoperative radiotherapy. The Cox proportional hazards model was used to evaluate the role of polymorphic genotypes on relapse-free (RFS) and disease-specific (DSS) survival. Deletion polymorphism of GSTM1 gene was significantly associated with DSS. The rs1799793 variant allele showed significant protection in both DSS and RFS. Significant increase in RFS but not in DSS was observed with polymorphic rs13181. The combined analysis of GSTM1 and XPD polymorphisms revealed favorable effect on survival. GSTM1 and XPD variant alleles, independently as well as in combination may serve as important predictors of clinical outcome in radiotherapy-treated OSCC patients.

Implication of Polymorphisms in DNA Repair Genes in Prognosis of Hepatocellular Carcinoma

“…312 (Asp to Asn) and 751 (Lys to Gln) were the main two polymorphisms that induce amino acid changes in the proteins (Shen et al, 1998). The associations of the Lys751Gln polymorphism in XPD gene with the prognosis of various types of cancer have been widely reported in cancer epidemiologic studies, such as colorectal cancer, advanced lung cancer, oral cancer and pancreatic cancer (Giovannetti et al, 2011;Biason et al, 2012;Chen et al, 2012;Mahimkar et al, 2012;Slyskova et al, 2012). In our study, we have found polymorphism in XPD Lys751Gln is related to the prognosis of HCC, which has provided evidence that the XPD protein influences the overall survival of HCC through NER pathway.…”

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

“…ERCC2 is an evolutionary conservative DNA helicase, which is an important link of nucleotide excision repair pathways, involved in nucleotide excision repair and bases of transcription. Studies have found that ERCC2 RS13181 can predict clinical outcome in oral squamous cell carcinoma patients and in soft-tissue sarcoma patients treated with postoperative radiotherapy (Mahimkar et al, 2012;Szkandera et al, 2013). However, in patients with rectal cancer, we found that no association between RS13181 and response with a neoadjuvant radiochemotherapy.…”

No Association of XRCC1 and CLPTM1L Polymorphisms with Non-small Cell Lung Cancer in a Non-Smoking Han Chinese Population

“…Thus, DNA repair mechanisms are very important for maintaining genome integrity and preventing carcinogenesis. Base excision repair (BER) pathway is the key mechanism involved in repairing small base lesions in DNA that are the result of oxidation and alkylation damage (Hoeijmakers, 2001;Mahimkar et al, 2012), and was closely associated with lung cancer development (Qian and Massion, 2008). SNPs in susceptible genes have been increasingly emphasized on the grounds that XRCC1 is considered a crucial scaffold protein closely associated with the base excision repair pathway (Campalans et al, 2005).…”