CHRNA5 gene D398N polymorphism in Japanese lung adenocarcinoma.
BACKGROUND
Recently, to identify genetic factors that modify lung cancer risk, CHRNA5 non-synonymous variant amino acid position 398 (D398N) was identified. The site was a highly conserved in the second cellular loop of the nicotinic acetylcholine receptor subunit protein.


METHODS
We have investigated CHRNA5 gene polymorphism status in 302 surgically treated lung adenocarcinoma cases from Nagoya City University Hospital. The presence or absence of CHRNA5 polymorphism was analyzed by direct sequences. EGFR mutations status was already investigated and reported.


RESULTS
We detected nine cases (2.98%) of CHRNA5 polymorphism (D398N) in our cohort. Total EGFR mutations were present in 129 patients (42.7%). The polymorphism statuses were not correlated with gender (women; 2.1% versus men; 3.7%, P = 0.5119), smoking status (never smoker; 2.0% versus smoker; 4.0%, P = 0.3339), pathological stages (stage I; 2.6% versus stage II-IV; 3.8%, P = 0.7246), and EGFR mutation status of the lung adenocarcinomas (mutation; 2.3% versus wild type; 3.7%, P = 0.7373). In this analysis, CHRNA5 polymorphism (D398N) patients had significantly worse prognosis (5/9 were dead; mean survival = 27.1 mo) than the patients with CHRNA5 wild type (74/293 were dead; mean survival = 113.9 mo) (log-rank test; P = 0.0146).


CONCLUSIONS
Although CHRNA5 polymorphism is rare from Japanese lung cancer, polymorphism status might be correlated with shorter survival.
Sasaki
Hidefumi
H
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp
Hikosaka
Yu
Y
Okuda
Katsuhiro
K
Kawano
Osamu
O
Yukiue
Haruhiro
H
Yano
Motoki
M
Fujii
Yoshitaka
Y
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D017422:Sequence Analysis, DNA
C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic