Polymorphisms in the vitamin D receptor gene and risk of lung cancer.
BACKGROUND
Differences between the individual variations in DNA may modulate lung cancer process. Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms may influence the cancer risk due to their antiproliferative, antiangiogenic, antimetastatic and apoptotic effects.


METHODS
The genotype and haplotype frequencies of three polymorphisms of VDR, i.e. TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), were studied using PCR-RFLP in 137 patients with lung cancer and 156 controls.


RESULTS
Differences were observed in genotype (P=0.024) and allele (P=0.011) frequencies of TaqI polymorphism due to the "T" allele. Furthermore, compared with the "tt" genotype, the odds ratio for the "TT" genotype increased 2.24 times (95%CI=1.05-4.77, P=0.037). Comparing cases and controls, smoking habit (P=0.012) and gender distribution (P=0.005) were found to increase the risk of lung cancer in patients with "TT" homozygotes, demonstrating the role of gene-environment interaction in lung cancer. In addition, when age and gender within the case group only were evaluated in relation to genotype, the adjusted odds ratios for the "TT" genotype increased 2.20 times (95%CI=1.01-4.78, P=0.047) for age and 2.24 times (95%CI=1.05-4.80, P=0.037) for gender. However, no differences were observed for the distribution of variant genotypes of the BsmI and ApaI polymorphisms (P>0.05). To evaluate the joint effects of these polymorphisms, haplotype analysis was performed which showed that the haplotype baT was associated with higher lung cancer risk compared with the most common haplotype BAt (P=0.026).


CONCLUSIONS
This is perhaps the first study suggesting that TaqI polymorphism of the VDR gene might be a risk factor for lung cancer and that age, gender, and smoking habit could have an impact on lung cancer risk.
Dogan
Irem
I
Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
Onen
Hacer Ilke
HI
Yurdakul
Ahmet Selim
AS
Konac
Ece
E
Ozturk
Can
C
Varol
Ayhan
A
Ekmekci
Abdullah
A
D000368:Aged; D016022:Case-Control Studies; D004262:DNA Restriction Enzymes / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012044:Regression Analysis; D012907:Smoking / Q000235:genetics
D018167:Receptors, Calcitriol; D004262:DNA Restriction Enzymes