Single nucleotide polymorphisms of the TGFB1 gene and lung cancer risk in a Korean population

Kyong Hwa Park, Sle G. Lo Han, Young M. Whang, Hyo Jung Lee, Young Do Yoo, Jae Won Lee, Sang Won Shin, Yeul Hong Kim

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)39-44
Number of pages6
JournalCancer Genetics and Cytogenetics
Volume169
Issue number1
DOIs
Publication statusPublished - 2006 Aug 1
Externally publishedYes

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Transforming Growth Factor beta
Single Nucleotide Polymorphism
Lung Neoplasms
Population
Genes
Genotype
Genetic Promoter Regions
Odds Ratio
Luciferases
Gene Frequency
Non-Small Cell Lung Carcinoma
Codon
Smoking
History
Alleles
Confidence Intervals
Cell Line
DNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Single nucleotide polymorphisms of the TGFB1 gene and lung cancer risk in a Korean population. / Park, Kyong Hwa; Lo Han, Sle G.; Whang, Young M.; Lee, Hyo Jung; Yoo, Young Do; Lee, Jae Won; Shin, Sang Won; Kim, Yeul Hong.

In: Cancer Genetics and Cytogenetics, Vol. 169, No. 1, 01.08.2006, p. 39-44.

Research output: Contribution to journalArticle

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abstract = "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.",
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