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Polymorphisms in ERCC1 and Grade 3 or 4 Toxicity in Non–Small Cell Lung Cancer Patients

Massachusetts General Hospital and Harvard School of Public Health, Boston, Massachusetts

Request for reprints: David Christiani, Harvard School of Public Health, I-1407, 665 Huntington Avenue, Boston, MA 02115. Phone: 617-432-3323; Fax: 617-432-3441; E-mail: dchristi{at}hsph.harvard.edu.

Purpose: ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity.

Experimental Design: Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 polymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non–small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen.

Results: There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95% confidence interval, 1.07-5.05; P = 0.03).

Conclusions: Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a >2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non–small cell lung cancer patients.

Key Words: pharmacogenetics • toxicity • lung cancer

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