EGFR intron 1 dinucleotide repeat polymorphism is associated with the occurrence of skin rash with gefitinib treatment.
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 (lnOR) 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 lnOR 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.
Huang
Chin-Lun
CL
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Yang
Chih-Hsin
CH
Yeh
Kun-Huei
KH
Hu
Fu-Chang
FC
Chen
Kuan-Yu
KY
Shih
Jin-Yuan
JY
Lin
Zhong-Zhe
ZZ
Yu
Chong-Jen
CJ
Cheng
Ann-Lii
AL
Yang
Pan-Chyr
PC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018900:Dinucleotide Repeats; D005076:Exanthema / Q000209:etiology* / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D047668:Inteins / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
D011799:Quinazolines; D000077156:Gefitinib