Assessment of Nucleotide Excision Repair XPD Polymorphisms in the Peripheral Blood of Gemcitabine/Cisplatin–Treated Advanced Non–Small-Cell Lung Cancer Patients

• Published in: Clinical lung cancer Vol. 4; no. 4; pp. 237 - 241
• Main Authors: Camps, Carlos, Sarries, Carmen, Roig, Bárbara, Javier Sánchez, José, Queralt, Cristina, Sancho, Eva, Martinez, Natividad, Tarón, Miguel, Rosell, Rafael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2003
• Subjects: Chemotherapy resistance; Cockayne syndrome; DNA adducts; DNA repair; ERCC1; Transcription-coupled repair; Xeroderma pigmentosum genes; Cockayne syndrome; Chemotherapy resistance; ERCC1; DNA adducts; DNA repair; Transcription-coupled repair; Xeroderma pigmentosum genes
• ISSN: 1525-7304; 1938-0690
• DOI: 10.3816/CLC.2003.n.004

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.