Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer

Jin Sung Jang, Su Jeong Lee, Jin Eun Choi, Sung Ick Cha, Eung Bae Lee, Tae In Park, Chang Ho Kim, Won Kee Lee, Sin Kam, Je Yong Choi, Young Mo Kang, Rang Woon Park, In-San Kim, Young Lae Cho, Tae Hoon Jung, Sung Beom Han, Jae Yong Park

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The methyl-CpG binding domain 1 (MBD1) protein plays an important role for transcriptional regulation of gene expression. Polymorphisms and haplotypes of the MBD1 gene may have an influence on MBD1 activity on gene expression profiles, thereby modulating an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of MBD1 -634G>A, -501delT (-501 T/T, T/-, -/-), and Pro 401 Ala genotypes and their haplotypes with the risk of lung cancer in a Korean population. The MBD1 genotype was determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency matched for age and gender. The -634GG genotype was associated with a significantly increased risk of overall lung cancer compared with the -634AA genotype [adjusted odds ratio (OR), 3.10; 95% confidence interval (95% CI), 1.24-7.75; P = 0.016]. When analyses were stratified according to the tumor histology, the -634GG genotype was associated with a significantly increased risk of adenocarcinoma compared with the -634AA genotype (adjusted OR, 4.72; 95% CI, 1.61-13.82; P = 0.005). For the MBD1 -501delT and Pro 401 Ala polymorphisms, the -501 T/T genotype was associated with a marginal significantly increased risk of adenocarcinoma compared with the -501 -/- genotype (adjusted OR, 2.07; 95% CI, 1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype (adjusted OR, 3.41; 95% CI, 1.21-9.60; P = 0.02). Consistent with the genotyping analyses, the -634G/-501T/ 401 Pro haplotype was associated with a significantly increased risk of overall lung cancer and adenocarcinoma compared with the -634A/ -501 - / 401 Ala haplotype (adjusted OR, 1.44; 95% CI, 1.08-1.91; P = 0.012 and P c = 0.048; adjusted OR, 1.75; 95% CI, 1.20-2.56; P = 0.004 and P c = 0.016, respectively). On a promoter assay, the -634A allele had significantly higher promoter activity compared with the -634G allele in the Chinese hamster ovary cells and A549 cells (P < 0.05 and P < 0.001, respectively), but the -501delT polymorphism did not have an effect on the promoter activity. When comparing the promoter activity of the MBD1 haplotypes, the -634A/-501 - haplotype had a significantly higher promoter activity than the -634G/-501T haplotype (P < 0.001). These results suggest that the MBD1 -634G>A, -501delT, and Pro 401 Ala polymorphisms and their haplotypes contribute to the genetic susceptibility for lung cancer and particularly for adenocarcinoma.

Original languageEnglish
Pages (from-to)2474-2480
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number11 I
DOIs
Publication statusPublished - 2005 Jan 1
Externally publishedYes

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Lung Neoplasms
Haplotypes
Genotype
Genes
Odds Ratio
Confidence Intervals
Adenocarcinoma
Alleles
Methyl CpG Binding Domain
Gene Expression Regulation
Genetic Predisposition to Disease
Cricetulus
Transcriptome
Ovary
Histology
Healthy Volunteers
Population

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Jang, J. S., Lee, S. J., Choi, J. E., Cha, S. I., Lee, E. B., Park, T. I., ... Park, J. Y. (2005). Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer. Cancer Epidemiology Biomarkers and Prevention, 14(11 I), 2474-2480. https://doi.org/10.1158/1055-9965.EPI-05-0423

Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer. / Jang, Jin Sung; Lee, Su Jeong; Choi, Jin Eun; Cha, Sung Ick; Lee, Eung Bae; Park, Tae In; Kim, Chang Ho; Lee, Won Kee; Kam, Sin; Choi, Je Yong; Kang, Young Mo; Park, Rang Woon; Kim, In-San; Cho, Young Lae; Jung, Tae Hoon; Han, Sung Beom; Park, Jae Yong.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 14, No. 11 I, 01.01.2005, p. 2474-2480.

Research output: Contribution to journalArticle

Jang, JS, Lee, SJ, Choi, JE, Cha, SI, Lee, EB, Park, TI, Kim, CH, Lee, WK, Kam, S, Choi, JY, Kang, YM, Park, RW, Kim, I-S, Cho, YL, Jung, TH, Han, SB & Park, JY 2005, 'Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 11 I, pp. 2474-2480. https://doi.org/10.1158/1055-9965.EPI-05-0423
Jang, Jin Sung ; Lee, Su Jeong ; Choi, Jin Eun ; Cha, Sung Ick ; Lee, Eung Bae ; Park, Tae In ; Kim, Chang Ho ; Lee, Won Kee ; Kam, Sin ; Choi, Je Yong ; Kang, Young Mo ; Park, Rang Woon ; Kim, In-San ; Cho, Young Lae ; Jung, Tae Hoon ; Han, Sung Beom ; Park, Jae Yong. / Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2005 ; Vol. 14, No. 11 I. pp. 2474-2480.
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abstract = "The methyl-CpG binding domain 1 (MBD1) protein plays an important role for transcriptional regulation of gene expression. Polymorphisms and haplotypes of the MBD1 gene may have an influence on MBD1 activity on gene expression profiles, thereby modulating an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of MBD1 -634G>A, -501delT (-501 T/T, T/-, -/-), and Pro 401 Ala genotypes and their haplotypes with the risk of lung cancer in a Korean population. The MBD1 genotype was determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency matched for age and gender. The -634GG genotype was associated with a significantly increased risk of overall lung cancer compared with the -634AA genotype [adjusted odds ratio (OR), 3.10; 95{\%} confidence interval (95{\%} CI), 1.24-7.75; P = 0.016]. When analyses were stratified according to the tumor histology, the -634GG genotype was associated with a significantly increased risk of adenocarcinoma compared with the -634AA genotype (adjusted OR, 4.72; 95{\%} CI, 1.61-13.82; P = 0.005). For the MBD1 -501delT and Pro 401 Ala polymorphisms, the -501 T/T genotype was associated with a marginal significantly increased risk of adenocarcinoma compared with the -501 -/- genotype (adjusted OR, 2.07; 95{\%} CI, 1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype (adjusted OR, 3.41; 95{\%} CI, 1.21-9.60; P = 0.02). Consistent with the genotyping analyses, the -634G/-501T/ 401 Pro haplotype was associated with a significantly increased risk of overall lung cancer and adenocarcinoma compared with the -634A/ -501 - / 401 Ala haplotype (adjusted OR, 1.44; 95{\%} CI, 1.08-1.91; P = 0.012 and P c = 0.048; adjusted OR, 1.75; 95{\%} CI, 1.20-2.56; P = 0.004 and P c = 0.016, respectively). On a promoter assay, the -634A allele had significantly higher promoter activity compared with the -634G allele in the Chinese hamster ovary cells and A549 cells (P < 0.05 and P < 0.001, respectively), but the -501delT polymorphism did not have an effect on the promoter activity. When comparing the promoter activity of the MBD1 haplotypes, the -634A/-501 - haplotype had a significantly higher promoter activity than the -634G/-501T haplotype (P < 0.001). These results suggest that the MBD1 -634G>A, -501delT, and Pro 401 Ala polymorphisms and their haplotypes contribute to the genetic susceptibility for lung cancer and particularly for adenocarcinoma.",
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T1 - Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer

AU - Jang, Jin Sung

AU - Lee, Su Jeong

AU - Choi, Jin Eun

AU - Cha, Sung Ick

AU - Lee, Eung Bae

AU - Park, Tae In

AU - Kim, Chang Ho

AU - Lee, Won Kee

AU - Kam, Sin

AU - Choi, Je Yong

AU - Kang, Young Mo

AU - Park, Rang Woon

AU - Kim, In-San

AU - Cho, Young Lae

AU - Jung, Tae Hoon

AU - Han, Sung Beom

AU - Park, Jae Yong

PY - 2005/1/1

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N2 - The methyl-CpG binding domain 1 (MBD1) protein plays an important role for transcriptional regulation of gene expression. Polymorphisms and haplotypes of the MBD1 gene may have an influence on MBD1 activity on gene expression profiles, thereby modulating an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of MBD1 -634G>A, -501delT (-501 T/T, T/-, -/-), and Pro 401 Ala genotypes and their haplotypes with the risk of lung cancer in a Korean population. The MBD1 genotype was determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency matched for age and gender. The -634GG genotype was associated with a significantly increased risk of overall lung cancer compared with the -634AA genotype [adjusted odds ratio (OR), 3.10; 95% confidence interval (95% CI), 1.24-7.75; P = 0.016]. When analyses were stratified according to the tumor histology, the -634GG genotype was associated with a significantly increased risk of adenocarcinoma compared with the -634AA genotype (adjusted OR, 4.72; 95% CI, 1.61-13.82; P = 0.005). For the MBD1 -501delT and Pro 401 Ala polymorphisms, the -501 T/T genotype was associated with a marginal significantly increased risk of adenocarcinoma compared with the -501 -/- genotype (adjusted OR, 2.07; 95% CI, 1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype (adjusted OR, 3.41; 95% CI, 1.21-9.60; P = 0.02). Consistent with the genotyping analyses, the -634G/-501T/ 401 Pro haplotype was associated with a significantly increased risk of overall lung cancer and adenocarcinoma compared with the -634A/ -501 - / 401 Ala haplotype (adjusted OR, 1.44; 95% CI, 1.08-1.91; P = 0.012 and P c = 0.048; adjusted OR, 1.75; 95% CI, 1.20-2.56; P = 0.004 and P c = 0.016, respectively). On a promoter assay, the -634A allele had significantly higher promoter activity compared with the -634G allele in the Chinese hamster ovary cells and A549 cells (P < 0.05 and P < 0.001, respectively), but the -501delT polymorphism did not have an effect on the promoter activity. When comparing the promoter activity of the MBD1 haplotypes, the -634A/-501 - haplotype had a significantly higher promoter activity than the -634G/-501T haplotype (P < 0.001). These results suggest that the MBD1 -634G>A, -501delT, and Pro 401 Ala polymorphisms and their haplotypes contribute to the genetic susceptibility for lung cancer and particularly for adenocarcinoma.

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