Dose effect of cigarette smoking on frequency and spectrum of epidermal growth factor receptor gene mutations in Korean patients with non-small cell lung cancer.
OBJECTIVE
This study aimed to determine the dose effect of smoking on the mutational frequency and spectrum of epidermal growth factor receptor (EGFR) gene in Korean non-small cell lung cancer (NSCLC).


METHODS
Detailed smoking histories were obtained from 324 consecutively enrolled Korean NSCLC patients. Mutational status of EGFR (exon 18-21) was determined using nested polymerase chain reaction amplification.


RESULTS
A total of 108 EGFR mutations (33.3%) were identified in 107 patients. Decreased EGFR mutation rate with increased smoking dose was observed, with 48.0% (82 of 171) in never smokers, 23.1% (15 of 65) in former smokers, and 11.4% (10 of 88) in current smokers. The incidence of EGFR mutation was significantly lower in patients who smoked for more than 25 pack-years (P < 0.0001) or who stopped smoking cigarettes less than 10 years ago (P < 0.0001). Mutations in exon 19 or 21 were associated with fewer total smoke years (5.0 vs. 25.0 years in exon 20, P = 0.024), fewer total pack-years (6.3 vs. 38.9 pack-years in exon 20, P = 0.079), and more smoke-free years (11.1 vs. 3.6 years in exon 20, P = 0.027), compared with those in exon 20. Mutations in exon 19 or 21 were associated with female (P < 0.0001), never smoker (P < 0.0001), and adenocarcinoma (P < 0.0001), whereas those in exon 20 were not.


CONCLUSIONS
Smoking dosage affects the incidence of EGFR mutations. EGFR mutations in exon 19 or 21 are associated with low exposure to cigarette smoke, whereas EGFR mutation in exon 20 is more common in smokers.
Center for Clinical Trial, National Cancer Center, Gyeonggi, Republic of Korea.
Young Joo
YJ
Lee
Hyo Sub
HS
Shim
Young Ae
YA
Kang
Su Jung
SJ
Hong
Hyun Ki
HK
Kim
Hoguen
H
Kim
Se Kyu
SK
Kim
Sung Ho
SH
Choi
Joo-Hang
JH
Kim
Byoung Chul
BC
Cho
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007723:Korea; D016015:Logistic Models; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012907:Smoking
D066246:ErbB Receptors