Polymorphisms in the epidermal growth factor receptor gene and the risk of primary lung cancer: a case-control study.
BACKGROUND
Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population.


METHODS
We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls.


RESULTS
Of the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P = 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45-0.88, P = 0.007). When the analyses were stratified by smoking status, the protective effect of the TT genotype was statistically significant in ever-smokers (adjusted OR = 0.59, 95% CI = 0.41-0.86, P = 0.007), but not in never-smokers (adjusted OR = 0.89, 95% CI = 0.45-1.75, P = 0.73; P = 0.08, test for homogeneity). Consistent with the results of the genotyping analysis, the CGGCT haplotype with the 181946C allele was associated with a significantly increased risk of lung cancer compared to the CGGTT haplotype carrying the 181946T allele (adjusted OR = 1.50, 95% CI = 1.09-2.07, P = 0.012 and Bonferroni corrected P-value = 0.048).


CONCLUSIONS
These results suggest that the EGFR polymorphisms, particularly the 181945C>T polymorphism, could be used as markers for the genetic susceptibility to lung cancer.
Choi
Jin Eun
JE
Department of Biochemistry, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, 700-422, South Korea. ddochi74@hanmail.net
Park
Sun Ha
SH
Kim
Kyung Mee
KM
Lee
Won Kee
WK
Kam
Sin
S
Cha
Sung Ick
SI
Kim
Chang Ho
CH
Kang
Young Mo
YM
Kim
Young-Chul
YC
Han
Sung Beom
SB
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D017677:Age Distribution; D018288:Carcinoma, Small Cell / Q000453:epidemiology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007723:Korea / Q000453:epidemiology; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017678:Sex Distribution
D066246:ErbB Receptors