Predictive Value of Two Polymorphisms of ERCC2, rs13181 and rs1799793, in Clinical Outcomes of Chemotherapy in Gastric Cancer Patients: A Meta-Analysis

Abstract

Background Several researchers have investigated the relationship between ERCC2 rs13181 and rs1799793 polymorphisms and chemotherapy efficacy in terms of tumour response and prognosis in gastric patients. However, the published data have shown inconsistencies. Methods PubMed, Elsevier, and Chinese National Knowledge Infrastructure databases were searched for relevant articles published before August 1, 2017. Thirteen studies including 3096 gastric cancer patients treated with chemotherapy were included. Results For rs1799793, in the overall analyses, no relationships were found between four genetic models and clinical response (AA vs. GG: OR = 1.17, 95% CI, 0.70–1.95; GA vs. GG: OR = 0.94, 95% CI, 0.69–1.27; GA + AA vs. GG: OR = 1.12, 95% CI, 0.85–1.46; and AA vs. GG + GA: OR = 1.24, 95% CI, 0.81–1.92). In stratified analyses, the results remained negative. We also found no relationship between each of the genetic models and overall survival time in the overall analyses. In the stratified analyses, for Asians, the A carrier genotype might be more closely associated with shorter survival time and higher risk of death for patients than the GG genotype (AA vs. GG: HR = 1.77, 95% CI, 1.20–2.6; GA + AA vs. GG: HR = 1.62, 95% CI, 1.26–2.09), but the results were negative for Caucasians. No significant relationships were found between the rs13181 polymorphism and OR or OS. Conclusions This meta-analysis suggested that the ERCC2 rs1799793 polymorphism might be a predictor of prognosis in gastric cancer patients subjected to platinum-based chemotherapy.

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

“…Various genetic factors are predicted to affect treatment efficiency and prognosis in patients with HCC, such as X-ray cross-complementing group 1 ( XRCC1 ), X-ray repair cross-complementing group 3 ( XRCC3 ), and excision repair cross-complementation group 2 ( ERCC2 ). Many previous studies have investigated the associations between polymorphisms in these genes and prognosis [4–7]. In 2012, Jung et al [8] found that XRCC1 rs25487, ERCC5 rs2018836, ERCC5 rs3818356, and XRCC4 rs1805377 have significant effects on survival.…”

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

“…The DNA helicase encoded by the excision repair cross-complementing group 2 gene (ERCC2), also called xeroderma pigmentosum group D (XPD), is involved in basal cellular transcription and NER of DNA lesions [51]. To date, a number of studies have implicated the role of genetic polymorphism within ERCC2 gene in various cancers, such as gastric, pancreatic, glioma, bladder, and hepatocellular carcinoma [52][53][54][55][56][57]. The most studied polymorphisms rs13181 (Lys751Gln) and rs238406 (Arg156Arg) were demonstrated to alter the function of encoded protein, and, in consequence, influence on DNA repair capacity [58,59].…”

<p>Genetic Polymorphisms and the Efficacy of Platinum-Based Chemotherapy: Review</p>

“…The impact of these changes is related to the clinical outcome of chemotherapy's effectiveness, such as decreased response and survival. 99,100 In contrast to ABCC2, which is one of the MRP transporter families that encodes Multidrug Resistance-associated Protein 2, it functions as an organic anion transporter, playing a role in platinum-conjugated transport out of cells. C>T polymorphisms (rs717620) are associated with altered ABCC2 expression or function.…”