Association Between DNA-repair Polymorphisms and Survival in Pancreatic Cancer Patients Treated with Combination Chemotherapy

Giovannetti, Elisa; Pacetti, Paola; Reni, Michele; León, Leticia G.; Mambrini, Andrea; Vasile, Enrico; Ghidini, Michele; Funel, Niccola; Lucchesi, M; Cereda, Stefano; Peters, Godefridus J.; Cantore, Maurizio

doi:10.2217/pgs.11.109

Cited by 42 publications

(39 citation statements)

References 49 publications

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“…The findings of previous studies in NSCLC and pancreatic cancer patients were similar to ours with respect to XPD codon 751 polymorphisms (53,55,56). The negative results might be explained by the sample size that is not large enough to detect a small effect from SNPs of low penetrance, alternatively, due to exclusion of other DNA repair genes that might synergistically act with the analyzed genes in normal tissues.…”

Section: Discussionsupporting

confidence: 89%

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Cheng

Qin

Sun

et al. 2013

Technol Cancer Res Treat

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Platinum-based chemotherapy is a primary treatment for patients with advanced non-small cell lung cancer (NSCLC). Considering individual differences, an effective and convenient method is urgently needed to identify the sensitivity of individual patient to platinum based regimen. Genetic variants in DNA repair genes are presumed to represent important determinants of drug efficacy. Our previous studies have demonstrated the involvement of xeroderma pigmentosum group A (XPA) codon23 and xeroderma pigmentosum group D (XPD) codon751 single-nucleotide polymorphisms (SNPs) in clinical response to platinum based chemotherapy in advanced NSCLC patients. Thus, a follow-up study was carried out to investigate the relevance of these genotypes and survival of the cohort (n 5 115). The threedimensional (3-D), polyacrylamide gel-based DNA microarray method was used to assess the genotypes of XPA and XPD in peripheral lymphocytes. Log-rank test revealed that the variant genotypes of XPA23 (A/G1G/G) were associated with significantly longer progression-free survival (PFS) (6.0 m vs. 10.6 m, log-rank P 5 0.001) and overall survival (OS) (11.2 m vs. 20.8 m, log-rank P 5 0.001). In Cox proportional hazards model, the hazard ratio (HR) for death in patients with G allele was 0.65 (P 5 0.049). While no significant differences were observed in PFS or OS according to XPD Lys751Gln genotypes (log-rank P  0.05).In combination with our previous short-term clinical results, this study further confirmed that by detecting the SNPs in blood cells, XPA A23G polymorphic variants might be a promising biomarker in predicting a favor prognosis of NSCLC patients and be helpful towards designing individualized treatments.

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Section: Discussionsupporting

confidence: 89%

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Cheng

Qin

Sun

et al. 2013

Technol Cancer Res Treat

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“…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.…”

Section: Discussionsupporting

confidence: 69%

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

Yue¹,

Xie²,

Guo³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…XRCC1 gene polymorphisms are reported to be correlated with the treatment outcome of cisplatin-based chemotherapy in several kinds of cancers, such as gastric cancer, colorectal cancer, nasopharyngeal cancer, ovarian cancer, pancreatic cancer, and esophageal cancer (Warnecke-Eberz et al, 2009;Giovannetti et al, 2011;Miao et al, 2012;Chen et al, 2013;Cao et al, 2014;Wu et al, 2014). Currently, several studies have reported the association between XRCC1 genetic polymorphisms and treatment outcome of advanced NSCLC (Yuan et al, 2006;Wang et al, 2004Wang et al, , 2008Sun et al, 2009;Li et al, 2011;Ke et al, 2012;Han et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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

Mao

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementing group 1 (XRCC1) genetic variations may influence the efficacy of chemotherapy in various cancers. We investigated the possible roles of GSTP1 Ile105Val and XRCC1 Arg194Trp, and Arg399Gln gene polymorphisms in the prognosis of advanced non-small cell lung carcinoma (NSCLC) patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, this study consecutively recruited 141 patients with advanced NSCLC from the First People's Hospital of Yunnan Province. Logistic regression analysis showed that individuals carrying the GG genotype were associated with a better response to chemotherapy than those with the wide-type genotype, with an adjusted odds ratio (95% confidence interval, CI) of 4.07 (1.06-25.06). Moreover, we observed that the AA genotype of XRCC1 Arg399Gln was correlated with a greater complete response + partial response to chemotherapy than that with the GG genotype (odds ratio = 2.71, 95%CI = 1.13-10.08). Based on the Cox hazard proportional model, the GG genotype of GSTP1 Ile105Val was found to be associated with a lower risk of death from all causes as compared to that with the AA genotype (hazard ratio = 0.07, 95%CI = 0.01-0.34). In summary, we suggest that GSTP1 Ile105Val and XRCC1 Arg399Gln polymorphisms could influence the response to chemotherapy and survival of advanced NSCLC.

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Association Between DNA-repair Polymorphisms and Survival in Pancreatic Cancer Patients Treated with Combination Chemotherapy

Cited by 42 publications

References 49 publications

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

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

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

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