Glu346Lys polymorphism in the methyl-CpG binding domain 4 gene and the risk of primary lung cancer.
BACKGROUND
Methyl-CpG binding domain 4 (MBD4) protein functions as a DNA repair enzyme and minimizes mutations at 5-methylcytosine. Polymorphisms in the DNA repair gene MBD4 may be associated with differences in DNA repair capacity and thereby influence an individual's susceptibility to lung cancer. To test this hypothesis, we examined the potential association between the MBD4 Glu346Lys polymorphism and the risk of lung cancer in a Korean population.


METHODS
The MBD4 Glu346Lys genotypes were determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects.


RESULTS
The distribution of the MBD4 Glu346Lys genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by tumor histology, the Lys346Lys genotype was associated with a significantly decreased risk of adenocarcinoma (AC) as compared with the Glu346Glu genotype [adjusted odds ratio (OR) = 0.50, 95% confidence interval (CI) = 0.26-0.97, P = 0.04]. On the stratification analysis, the protective effect of the Lys346Lys genotype against AC was statistically significant in older individuals and heavier smokers (adjusted OR = 0.08, 95% CI = 0.01-0.64, P = 0.02; and adjusted OR = 0.09, 95% CI = 0.01-0.72, P = 0.02, respectively).


CONCLUSIONS
Our findings suggest that the MBD4 Glu346Lys polymorphism could be used as a marker for genetic susceptibility to AC of the lung.
Shin
Moo Chul
MC
Department of Internal Medicine, Kyungpook National University, Daegu, Korea.
Lee
Su Jeong
SJ
Choi
Jin Eun
JE
Cha
Sung Ick
SI
Kim
Chang Ho
CH
Lee
Won Kee
WK
Kam
Sin
S
Kang
Young Mo
YM
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D044503:5-Methylcytosine / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
D014408:Biomarkers, Tumor; D044503:5-Methylcytosine; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human