Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Only about one third of non-small-cell lung cancer (NSCLC) patients respond to cisplatin-based chemotherapy. Cisplatin DNA adducts are commonly repaired through the nucleotide excision repair pathway. The study of rare inherited disorders such as xeroderma pigmentosum and Cockayne syndrome has disclosed that XP genes, including XPD, play an essential role in DNA repair, both in the global genomic repair and in the transcription-coupled repair pathways. XPD polymorphism and decreased expression of XP genes have both been linked to lower DNA repair capacity. ERCC1 overexpression has been associated with cisplatin resistance, and experimental evidence shows a close association between ERCC1 and XPD. In the present study, we have examined XPD polymorphisms at codons 751 and 312 in DNA isolated from peripheral blood in 39 patients with gemcitabine/cisplatin-treated locally advanced non-small-cell lung cancer Although no significant correlation was observed between XPD genotype and objective response, a trend toward better response was observed in patients with XPD polymorphism at codon 312. The map of the nucleotide excision repair pathway can be used to design translational research studies to identify and validate predictive markers of response to cisplatin, and the Spanish Lung Cancer Group has recently accrued 250 gemcitabine/cisplatin-treated NSCLC patients for a prospective assessment of XPD genotype
Clin Lung Cancer 2003 Jan
PMID:Assessment of nucleotide excision repair XPD polymorphisms in the peripheral blood of gemcitabine/cisplatin-treated advanced non-small-cell lung cancer patients. 1462 13

ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) as genes have been known to be belonged to the nucleotide excision repair pathway and therefore related to DNA repair. Polymorphisms in these genes have been rarely evaluated in terms of predicting cancer patient survival. We investigated whether these polymorphisms have an effect on response to chemotherapy and survival in 109 patients with non-small-cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms of ERCC1 Asn118Asn (C --> T), XPD Lys751Gln (A --> C) and Asp312Asn (G --> A) were evaluated using a SNaPshot kit. As for chemotherapy response, treatment response did not show statistically significant differences between the wild genotypes and the variant genotypes for the ERCC1 and XPD gene. The median survival time of all patients was 376 days (95% CI, 291-488). As for survival rate according to the polymorphism of codon 118 in ERCC1, median survival time in patients showing C/C genotype was 486 days (95% CI, 333-x), which was significantly different from the 281 days (95% CI, 214-376) of patients with the variant genotype (T/T or C/T) (P = 0.0058). Using the Cox-proportional hazards model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight loss and performance status effected overall survival significantly (P = 0.0001, 0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751 and 312 in the XPD gene did not affect patient survival (P = 0.4711 and 0.4542, respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1 is a surrogate marker for predicting better survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.
Lung Cancer 2004 Jun
PMID:Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. 1514 May 44

Polymorphisms in nucleotide excision repair genes have been associated with risk for lung cancer. We examined gene-environment interactions in relation to lung cancer in 430 cases and 790 comparison persons identified within a prospective cohort of 57,053 persons. We included polymorphisms in the XPC, XPA and XPD genes involved in the nucleotide excision DNA repair pathway and analysed possible interactions with smoking and dietary intake of fruit and vegetables in relation to risk for lung cancer. We found that intake of fruit was associated with lower risk for lung cancer only among carriers of the XPA A23G variant genotype. The incidence rate ratio for lung cancer was 0.60 (95% confidence interval: 0.43-0.84; p=0.003) per 50% increase in fruit intake. No convincing interactions were detected between the polymorphisms and smoking.
Lung Cancer 2008 Feb
PMID:Polymorphisms in nucleotide excision repair genes, smoking and intake of fruit and vegetables in relation to lung cancer. 1791 80

Polymorphisms in DNA repair genes were thought to represent important determinants of platinum drug efficacy. This study tested whether XPD Lys751Gln and XRCC1 T-77C polymorphisms were associated with survival in platinum-treated patients with advanced non-small-cell lung cancer (NSCLC). In this study, 199 advanced NSCLC patients with platinum-based chemotherapy were recruited. During the median 26.5 months of follow-up, patients with the XPD 751Lys/Lys genotype had a median survival time of 17.0 months (95% CI, 14.5-19.6 months), not much longer than those carried Lys/Gln heterozygote (12.0 months; 95% CI, 3.4-20.6 months; log-rank test, P=0.542). In Cox proportional hazards model, no significant associations were found between XPD Lys751Gln polymorphism and survival. For XRCC1 T-77C polymorphism, the median survival of patients with TC+CC genotype (18 months; 95% CI, 13.5-22.5 months) was similar to those with the TT genotype (16.0 months; 95% CI, 13.3-18.7 months; log-rank test, P=0.399). XRCC1 T-77C polymorphism was not associated with survival in Cox proportional hazards model. Additionally, the analysis for combination of these two polymorphisms also showed no prognostic significance for NSCLC. Our findings indicated that neither XPD Lys751Gln nor XRCC1 T-77C could be genetic determinant for prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.
Lung Cancer 2011 Jul
PMID:Assessment of XPD Lys751Gln and XRCC1 T-77C polymorphisms in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. 2112 12

Individual differences in chemosensitivity and clinical outcome of non-small-cell lung carcinoma (NSCLC) patients can be influenced by host-inherited factors. We investigated the impact of XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp, and XPD Lys751Gln gene polymorphisms on treatment efficacy in 375 NSCLC patients on platinum-based chemotherapy. We also examined progression-free survival and overall survival. The gene polymorphisms were analyzed by duplex PCR. The patients with XRCC1 399A/A had a significantly better response to chemotherapy. Individuals with XPD 711 Asp and XPD 312 Asn alleles responded poorly to chemotherapy when compared with the wide-type genotype. The adjusted hazard ratio (HR) in the Cox regression model was calculated. The XRCC1 399A/A polymorphism was associated with better progression free survival and overall survival of NSCLC patients (HR=0.61 and 0.55). On the other hand, the XPD 711 Asp allele was associated with poorer progression free survival and overall survival compared to the C/C genotype, with HRs of 1.89 and 1.90. The XPD 312 Asn allele was found to be associated with non-significantly reduced survival of NSCLC patients (HR = 1.73). In conclusion, we found the polymorphisms of XRCC1 and XPD to be related to the efficacy of platinum-based chemotherapy in NSCLC patients. This information should aid in therapeutic decisions for individualized therapy in NSCLC cases.
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PMID:Pharmacogenetics of DNA repair gene polymorphisms in non-small-cell lung carcinoma patients on platinum-based chemotherapy. 2444 15