Impact of environmental tobacco smoke on the incidence of mutations in epidermal growth factor receptor gene in never-smoker patients with non-small-cell lung cancer.
OBJECTIVE
Active tobacco smoking has been associated with the incidence of epidermal growth factor receptor (EGFR) mutations. However, the impact of environmental tobacco smoke (ETS) on EGFR mutations has been unknown. We investigated an association between ETS exposure and EGFR mutations in never smokers with non-small-cell lung cancer (NSCLC).


METHODS
We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18 to 21 on EGFR gene were determined using nested polymerase chain reaction amplification.


RESULTS
The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% v 61.4%; P = .008). In a logistic regression model that adjusted for sex and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% CI, 0.20 to 0.81; P = .011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23 to 1.49), 0.50 (95% CI, 0.17 to 1.50), 0.48 (95% CI, 0.20 to 1.18), and 0.22 (95% CI, 0.08 to 0.62; P(trend) = .028). Among the types of ETS exposure, adulthood ETS and household ETS were significantly associated with the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% v 44.8%; P = .053).


CONCLUSIONS
ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.
Lee
Young Joo
YJ
Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Republic of Korea.
Cho
Byoung Chul
BC
Jee
Sun Ha
SH
Moon
Jin Wook
JW
Kim
Se Kyu
SK
Chang
Joon
J
Chung
Kyung Young
KY
Park
In Kyu
IK
Choi
Sung Ho
SH
Kim
Joo-Hang
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D066246:ErbB Receptors