Yonsei Med J.  2012 Nov;53(6):1128-1135. 10.3349/ymj.2012.53.6.1128.

EGFR Polymorphism as a Predictor of Clinical Outcome in Advanced Lung Cancer Patients Treated with EGFR-TKI

• Jung M
• Cho BC
• Lee CH
• Park HS
• Kang YA
• Kim SK
• Chang J
• Kim DJ
• Rha SY
• Kim JH
• Lee JH

• KMID: 1414254
• DOI: http://doi.org/10.3349/ymj.2012.53.6.1128

Abstract

PURPOSE
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.
MATERIALS AND 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.
CONCLUSION
SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.

Keyword

Polymorphism; lung cancer; EGFR tyrosine kinase inhibitor

MeSH Terms

Adult
Aged
Aged, 80 and over
Female
Genotype
Humans
Introns/genetics
Kaplan-Meier Estimate
Lung Neoplasms/*drug therapy/*genetics
Male
Middle Aged
Polymorphism, Single Nucleotide/genetics
Protein Kinase Inhibitors/*therapeutic use
Receptor, Epidermal Growth Factor/*antagonists & inhibitors/*genetics
Treatment Outcome

Figure

• 

  Fig. 1 Kaplan-Meier curve of progression-free survival according to genotype. (A) SNP-216. (B) CA-SSR1 length. SNP, single nucleotide polymorphism; CA-SSR1, CA simple sequence repeat in intron 1; PFS, progression-free survival.

• 

  Fig. 2 Kaplan-Meier curve of overall survival according to genotype. (A) SNP-216. (B) CA-SSR1 length. SNP, single nucleotide polymorphism; CA-SSR1, CA simple sequence repeat in intron 1; OS, overall survival.

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