Pharmacogenetics of DNA repair gene polymorphisms in non-small-cell lung carcinoma patients on platinum-based chemotherapy.
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.
Department of General Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
L
L
Zhang
Department of General Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China xiandongli67@126.com.
W
W
Ma
Department of General Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Y
Y
Li
Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
J
J
Wu
Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
G Y
GY
Shi
D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D016190:Carboplatin; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human