EGFR polymorphism of the kinase domain in Japanese lung cancer.
BACKGROUND
Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy.


METHODS
We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center.


RESULTS
EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers.


CONCLUSIONS
EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers.
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp
Hidefumi
H
Sasaki
Katsuhiko
K
Endo
Minoru
M
Takada
Masaaki
M
Kawahara
Hisaichi
H
Tanaka
Naoto
N
Kitahara
Akihide
A
Matsumura
Keiji
K
Iuchi
Tomoya
T
Kawaguchi
Katsuhiro
K
Okuda
Osamu
O
Kawano
Haruhiro
H
Yukiue
Tomoki
T
Yokoyama
Motoki
M
Yano
Yoshitaka
Y
Fujii
D000230:Adenocarcinoma / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib