EGFR intron 1 dinucleotide repeat polymorphism is associated with the occurrence of skin rash with gefitinib treatment
Journal
Lung Cancer
Journal Volume
64
Journal Issue
3
Pages
346-351
Date Issued
2009
Author(s)
Huang C.-L.
Hu F.-C.
Abstract
Background: Skin rash is the most common toxicity of epidermal growth factor receptor (EGFR)-targeted therapy. This study investigated the clinical and genetic factors associated with this skin rash. Methods: Fifty-two non-small cell lung cancer patients enrolled in a clinical trial of first-line gefitinib treatment were genotyped for EGFR intron 1 CA repeat ([CA]n) polymorphism and single nucleotide polymorphisms at G-216T, C-191A, and R521K. The severity of skin rash was correlated with the genotypic and clinicopathological features. Results: Seventeen patients (32.7%) developed grade 2-3 skin rashes within 4 weeks of treatment (early G2/3 rash). In the multivariate logistic regression analysis, only the [CA]n genotype was correlated with early G2/3 rash; and this relationship was modified by age. Early G2/3 rash developed in 21% of patients with homozygous long allele (19-22 repeats, L) genotype, 31% with heterozygous short allele (15-18 repeats, S)/L genotype, and 71% with S/S genotype, respectively. The estimated logarithm of odds ratio (ln OR) for early G2/3 rash, as compared to S/S genotype, for S/L genotype was -0.038 multiplied by age (P = 0.011); and the ln OR for L/L genotype was -0.050 multiplied by age (P = 0.004). Early G2/3 rash was correlated with tumor response in the multiple logistic regression analysis (P = 0.027). However, the [CA]n genotype was not significantly correlated with tumor response (P = 0.35). Conclusions: EGFR [CA]n genotype appears to be a useful predictive marker of the development of skin rashes with gefitinib treatment. ? 2008 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
dinucleotide; epidermal growth factor receptor; gefitinib; adult; aged; allele; article; clinical feature; clinical study; clinical trial; controlled study; correlation analysis; disease severity; dry skin; female; genotype; heredity; homozygote; human; human tissue; intron; lung adenocarcinoma; major clinical study; male; multivariate logistic regression analysis; paronychia; pathology; phase 2 clinical trial; prediction; priority journal; rash; risk; single nucleotide polymorphism; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Dinucleotide Repeats; Exanthema; Female; Genes, erbB-1; Humans; Inteins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pharmacogenetics; Polymorphism, Genetic; Quinazolines; Treatment Outcome
Type
journal article