EGFR polymorphism as a predictor of clinical outcome in advanced lung cancer patients treated with EGFR-TKI.
OBJECTIVE
Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI.


METHODS
A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated.


RESULTS
SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI.


CONCLUSIONS
SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.
Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters and Research Center for Human Natural Defense System, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Korea.
Minkyu
M
Jung
Byoung Chul
BC
Cho
Chul Ho
CH
Lee
Hyung Soon
HS
Park
Young Ae
YA
Kang
Se Kyu
SK
Kim
Joon
J
Chang
Dae Jun
DJ
Kim
Sun Young
SY
Rha
Joo Hang
JH
Kim
Ji Hyun
JH
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors