Common variations of DNA repair genes are associated with response to platinum-based chemotherapy in NSCLCs

Area of Science:

• Oncology
• Genetics
• Pharmacogenomics

Background:

• Individual responses to chemotherapy vary significantly in non-small-cell lung cancer (NSCLC).
• Host inherited factors, including genetic polymorphisms, are suspected to influence chemosensitivity and clinical outcomes.
• The Xeroderma pigmentosum group D (XPD) gene plays a role in DNA repair, potentially affecting chemotherapy efficacy.

Purpose of the Study:

• To investigate the association between specific XPD gene polymorphisms (Arg156Arg, Asp312Asn, Asp711Asp, Lys751Gln) and the efficacy of platinum-based chemotherapy in NSCLC patients.
• To determine if these genetic variations can predict treatment response and survival outcomes.

Main Methods:

• A cohort of 496 NSCLC patients treated between 2003 and 2006 was analyzed.
• Genotyping for XPD Arg156Arg, Asp312Asn, Asp711Asp, and Lys751Gln polymorphisms was performed using duplex polymerase-chain-reaction.
• Patient outcomes, including response to chemotherapy, progression-free survival (PFS), and overall survival (OS), were followed up until 2011.

Main Results:

• Patients with XPD Asp312Asn (312 C/T+T/T) and XPD Asp711Asp (711 C/T+T/T) genotypes showed significantly poorer responses to platinum-based chemotherapy compared to wild-type.
• Adjusted odds ratios (ORs) for poor response were 0.67 (95% CI: 0.38-0.97) for XPD 312 C/T+T/T and 0.54 (95% CI: 0.35-0.96) for XPD 711 C/T+T/T.
• Cox regression analysis revealed that patients with these XPD genotypes had significantly lower median PFS and OS.

Conclusions:

• Polymorphisms in the XPD gene are associated with treatment response to platinum-based chemotherapy in NSCLC.
• These findings suggest that XPD genotype may serve as a predictive biomarker for chemotherapy efficacy.
• The results support the potential for individualized therapy decisions in NSCLC based on XPD genetic profiles.