Single nucleotide polymorphisms of the TGFB1 gene and lung cancer risk in a Korean population.
The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the transforming growth factor-beta 1 (TGFB1) gene and susceptibility to lung cancer and the clinical effect of the SNPs on lung cancer progression in a Korean population. Two polymorphisms in the promoter region of the TGFB1 (T-1572C, C-509T), and one SNP in codon 10 (T+869C) were determined using a SNaPshot primer extension assay in 194 Korean lung cancer patients and 283 normal controls. The polymorphic allele frequencies of A-1572G, C-509T, and T+869C were similar among lung cancer patients (0.52, 0.47, and 0.47, respectively) and controls (0.54, 0.46, and 0.44, respectively). When the data was stratified for smoking history, patients who smoked heavily and had heterozygous C-509T and T+869C genotypes showed an increased lung cancer risk (odds ratio OR = 3.77, confidence interval 95% CI = 1.25-11.30, P = 0.017; OR = 3.61, 95% CI = 1.21-10.74, P = 0.021 for each), after adjustment for age and sex. When heterozygous and homozygous variants for each SNPs were analyzed together, patients who were smokers and had variant genotypes also showed increased risk compared to the reference group. Further analyses to test the effect of the SNPs on the clinical parameters did not reveal an association of each polymorphic allele to the tumor stage or response to treatment. In addition, DNA fragments containing polymorphic genotype of the promoter region (-509T) showed increased transcriptional activity in luciferase assays using non-small cell lung cancer cell lines. In conclusion, this study suggests that heavy smokers in this Korean population who have specific polymorphic variants, which have been associated with increased transcriptional activity of TGFB1, might be more vulnerable to lung cancer.
Park
Kyong Hwa
KH
Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
Lo Han
Sle Gi
SG
Whang
Young Mi
YM
Lee
Hyo Jung
HJ
Yoo
Young Do
YD
Lee
Jae Won
JW
Shin
Sang Won
SW
Kim
Yeul Hong
YH
D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D007723:Korea; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*
D017931:DNA Primers; D016212:Transforming Growth Factor beta