Originally published as JCO Early Release 10.1200/JCO.2006.05.8768 on August 8 2006

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DNA-Repair Gene Polymorphisms Predict Favorable Clinical Outcome Among Patients With Advanced Squamous Cell Carcinoma of the Head and Neck Treated With Cisplatin-Based Induction Chemotherapy

Miguel Quintela-Fandino, Ricardo Hitt, Pedro P. Medina, Soledad Gamarra, Luis Manso, Hernan Cortes-Funes, Montserrat Sanchez-Cespedes

Medical Oncology Department. University Hospital 12 de Octubre. Madrid, Spain
Lung Cancer Group. Molecular Pathology Programme. Spanish National Cancer Centre (CNIO), Madrid, Spain
Molecular Biology Division, Hematology Department. University Hospital 12 de Octubre, Madrid, Spain

Address reprint requests to Miguel Quintela-Fandino, MD, PhD, The Ontario Cancer Institute, University Institute for Breast Cancer Research. 620 University Ave, Toronto M5G2M9, Canada; e-mail: quintelamiguel2000{at}yahoo.es

Purpose: Cisplatin kills tumor cells through DNA cross linking. Alterations in the function of DNA repair genes may affect DNA repair proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN).

Methods: A polymerase chain reaction–restriction fragment length polymorphism (RFLP) approach was used to determine the frequency of the SNPs: XPD-Asp312Asn, XPD-Lys751Gln, ERCC1-C8092A, and XRCC1-Arg399Gln in DNA from peripheral lymphocytes of 103 stage IV SCCHN patients.

Results: The frequencies of the distinct genotypes were, respectively, for the homozygous common allele, heterozygous and homozygous polymorphic variant: 53%, 40%, and 7% for ERCC1; 50%, 42%, and 8% for XPD-312; 35%, 57%, and 8% for XPD751; and 35%, 51%, and 13% for XRCC1. Patients with only common alleles at all the SNPs tested had a median overall survival of 5.1 months (range, 4.3 to 6.0 months) as compared with not reached for patients with at least one polymorphic variant (P < .001). Estimates from Cox's multivariate analysis suggest that the accumulation of each polymorphic variant decreases the probability of dying by a factor of 2.1 (P < .001; the presence of seven polymorphic variants confers a 175-fold protection). The accumulation of polymorphic variants increases by 2.94-fold the probability of achieving a complete response to treatment (P = .041).

Conclusion: Using a multivariate model, the presence of polymorphic variants in DNA-repair genes are powerful prognosis factors and response to cisplatin predictors among SCCHN patients.

published online ahead of print at www.jco.org on August 7, 2006.

Supported by a fellowship from the Comunidad Autonoma de Madrid (P.P.M.).

Presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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