Effect of ERCC1 Polymorphisms and the Modification by Smoking on the Survival of Non-Small Cell Lung Cancer Patients

Abstract

A few reports for ERCC1 SNPs were conducted in patients treated with cisplatin chemotherapy. The aim of this study is to determine whether the SNPs are a prognostic factor related to the treatment or not and if smoking level of the patients have any relationship to the SNPs' effect on the survival. Peripheral blood lymphocytes of 423 consecutive non-small cell lung cancer patients were examined: 245 of the patients received cisplatin combination chemotherapy and 178 received only conservative care. We examined ERCC1 SNPs (codon 118 C/T and 8092 C/A). Whereas ERCC1 118 SNP had no effect on the survival in patients' given no treatment, an effect of the SNP was observed in the treatment group, especially in stage III. When smoking was considered, the risk effect of the T allele was shown to be significantly associated with the group that had more than 50 pack yr (p=0.03). As for the ERCC1 8092 C/A, no significant effects were observed in the treated group and the non-treatment group. These findings may suggest that the ERCC1 118 SNP is an useful prognostic factor related to cisplatin therapy and the effect of this polymorphism appears to be modified by smoking.

ERCC1SNPs as Potential Predictive Biomarkers in Non-Small Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy

“…However, conflicting results have been reported by other investigators, demonstrating that any copies of the A allele were associated with shorter survival in NSCLC patients (21)(22)(23). On the other hand, a few studies with larger sample size than ours have reported that ERCC1-C8092A polymorphism had no influence on survival in NSCLC patients (8,15). In the above-mentioned studies, the stage of the disease as well as the tumor histology, chemotherapy regimen, and race of the subjects were different.…”

Genetic Effect of ERCC1 Codon 118 Polymorphism and Confounding Factors

“…For example, a case-control study showed the presence of a gene-smoking interaction with the ERCC1 polymorphism (5). This interaction was also observed in our recent study (6). Prognostic significance was observed only in those patients with non -small cell lung cancer who were heavy smokers (z50 pack-years; P = 0.03, using the log-rank test).…”

The platinum-based treatments for advanced non-small cell lung cancer, is low/negative ERCC1 expression better than high/positive ERCC1 expression? A meta-analysis

“…So, differences in ERCC1 expression may not affect the survival of women receiving platinum-based treatments. ERCC1 polymorphisms are also associated with response to treatment and overall survival in advanced NSCLC patients treated with platinum-based chemotherapy [43][44][45][46][47][48], though some authors have discordant results [49,50].…”