Genetic polymorphism of GSTP1 and ERCC1 correlated with response to platinum-based chemotherapy in non-small cell lung cancer

Abstract

The study aims to investigate whether the glutathione S transferase P1 (GSTP1) and excision repair cross-complementing group 1 (ERCC1) polymorphism influence the response to treatment with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer. Ninety-one patients with metastatic non-small lung cancer were evaluated. Blood samples were obtained from each patient before chemotherapy. They are all administered modified TP, GP, NP regimens. Curative effects in patients were evaluated after at least two cycles of treatment. TTP was calculated. The response rate of GSTP1 with G/G + G/A group and A/A group is 54.55 % (24/44) and 21.28 % (10/47) (P = 0.001), respectively. The response rate of ERCC1 with C/C group and C/T + T/T group is 51.11 % (23/45) and 23.91 % (11/46) (P = 0.007), respectively. Patients with both G/G + G/A and C/C has the response rate of 64.52 % (20/31) (P = 0.000). Logistic regression analysis shows a significant increased chance of treatment response in patients with G/G + G/A genotype versus A/A genotype (P = 0.008) and with T/T + C/T genotype versus C/C genotype (P = 0.001). The median TTP of all patients is 7.32 months. The TTP of individuals with G/G + G/A genotype is 9.56 months, and those with A/A genotype had an TTP of 5.23 months. The TTP of individuals with C/C genotype is 9.16 months, and those with T/T + C/T genotype is 5.53 months. Kaplan-Meier analysis shows that ERCC1 and GSTP1 polymorphisms are correlated with TTP. The log-rank test is was marginally significant (P < 0.01). GSTP1 and ERCC1 polymorphism are correlated with response to platinum-based chemotherapy and have prognostic value for TTP.

ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer

“…The predictive value of ERCC1 expression in platinum-based chemotherapy responses has been reported in various cancers such as non-small cell cancer, ovarian cancer, and cervical cancer, as well as BC (Dabholkar et al, 1994;Kong et al, 2006;Bellmunt et al, 2007;Chen et al, 2010;Hoffmann et al, 2010;Okuda et al, 2011;Park et al, 2011;Cheng et al, 2012;Lv et al, 2014). A systemic review published in 2012 further confirmed the predictive value of ERCC codon C118T polymorphism in advanced colorectal patients treated with platinum-based chemotherapy in the Asian population.…”

GSTP1 Ile105Val and XRCC1 Arg399Gln gene polymorphisms contribute to the clinical outcome of patients with advanced non-small cell lung cancer

“…Currently, some studies have investigated the association between genetic polymorphisms in the GSTP1 IIe105Val region and the prognosis of advanced NSCLC, but the results are inconclusive (Ada et al, 2010;Zhou et al, 2011;Ke et al, 2012;Lv et al, 2014;Yang and Zhao, 2014;Deng et al, 2015;Han et al, 2015;Liu et al, 2015). Individuals with GSTP1 gene polymorphisms display a reduced ability to detoxify drug metabolites, thus promoting the overall survival of NSCLC (Lu et al, 2006;Ke et al, 2012;Lv et al, 2014;Deng et al, 2015;Han et al, 2015).…”

“…Individuals with GSTP1 gene polymorphisms display a reduced ability to detoxify drug metabolites, thus promoting the overall survival of NSCLC (Lu et al, 2006;Ke et al, 2012;Lv et al, 2014;Deng et al, 2015;Han et al, 2015). Four studies reported that the Val allele of GSTP1 IIe105Val obtained a better response to chemotherapy and a better survival time when compared to IIe allele in Asian population (Ada et al, 2010;Zhou et al, 2011;Ke et al, 2012;Lv et al, 2014;Han et al, 2015). Two studies suggested that the Val allele of GSTP1 IIe105Val was more highly correlated with a poor response to chemotherapy than those carrying the IIe genotype (Deng et al, 2015;Liu et al, 2015).…”

Glutathione S-transferase pi polymorphism contributes to the treatment outcomes of advanced non-small cell lung cancer patients in a Chinese population

“…Many studies have reported the relationship between GSTP1 polymorphisms and prognosis of advanced NSCLC, but the results are inconclusive (Booton et al, 2006;Lu et al, 2006;Vlachogeorgos et al, 2008;Kalikaki et al, 2009;Sun et al, 2010;Lv et al, 2014;Han et al, 2015). Sun et al (2010), Han et al (2015) and Lv et al, (2014) conducted studies in Chinese populations and reported that GSTP1 genetic variations might be the predictive markers for the treatment outcome of advanced NSCLC.…”

“…Sun et al (2010), Han et al (2015) and Lv et al, (2014) conducted studies in Chinese populations and reported that GSTP1 genetic variations might be the predictive markers for the treatment outcome of advanced NSCLC. Booton et al (2006), Vlachogeorgos et al (2008) and Lu et al (2006) carried out studies in Caucasians and they reported that GSTP1 polymorphisms may predict response to treatment and survival in patients with advanced NSCLC.…”