Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer

Jae Sook Sung, S. G L Han, Young M. Whang, Eun Soon Shin, Jae Won Lee, Hyo Jung Lee, Jeong Seon Ryu, In Keun Choi, Kyong Hwa Park, Jun Suk Kim, Sang Won Shin, Elizabeth K. Chu, Yeul Hong Kim

Research output: Contribution to journalArticle

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Abstract

The RASSF1 gene, a putative tumor suppressor gene located on human chromosome 3p21, has attracted a great deal of attention because of frequent allelic loss and gene silencing via promoter hypermethylation in a variety of human malignancies. To evaluate the role of RASSF1A gene in lung cancer risk, genotypes of the RASSF1A promoter region (-710 C > T and -392 T > C) were determined in 410 lung cancer patients and 410 normal subjects. Furthermore, to examine potential effects of the common haplotypes (C-C, T-T and C-T haplotypes) on RASSF1A transcription, luciferase reporter assays were performed in H2009 and H358 non-small cell lung cancer (NSCLC) cell lines. We found that ht2 C-T haplotype was associated with susceptibility to the risk of lung cancer in dominant (odds ratio (OR): 0.69; 95% CI: 0.46-0.99) model. In particular, we found that C-T haplotype showed a decreased risk of lung cancer in males (codominant OR: 0.59; 95% CI: 0.38-0.93 and dominant OR: 0.58; 95% CI: 0.35-0.96) and in smokers (codominant OR: 0.58; 95% CI: 0.36-0.93 and dominant OR: 0.56; 95% CI: 0.33-0.96). Interestingly, C-T haplotype induced transcriptional activity by 50-60% compared with other haplotypes in NSCLC cell lines. These results suggest that RASSF1A promoter polymorphisms affect RASSF1A expression, further contributing to the genetic susceptibility to lung cancer.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalLung Cancer
Volume61
Issue number3
DOIs
Publication statusPublished - 2008 Sep 1

Fingerprint

Haplotypes
Single Nucleotide Polymorphism
Lung Neoplasms
Odds Ratio
Non-Small Cell Lung Carcinoma
Cell Line
Loss of Heterozygosity
Human Chromosomes
Gene Silencing
Genetic Predisposition to Disease
Tumor Suppressor Genes
Luciferases
Genetic Promoter Regions
Genes
Genotype
Neoplasms

Keywords

  • Haplotype
  • Lung cancer
  • RASSF1A
  • Single nucleotide polymorphism (SNP)
  • Transcriptional activity

ASJC Scopus subject areas

  • Oncology

Cite this

Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer. / Sung, Jae Sook; Han, S. G L; Whang, Young M.; Shin, Eun Soon; Lee, Jae Won; Lee, Hyo Jung; Ryu, Jeong Seon; Choi, In Keun; Park, Kyong Hwa; Kim, Jun Suk; Shin, Sang Won; Chu, Elizabeth K.; Kim, Yeul Hong.

In: Lung Cancer, Vol. 61, No. 3, 01.09.2008, p. 301-308.

Research output: Contribution to journalArticle

Sung, JS, Han, SGL, Whang, YM, Shin, ES, Lee, JW, Lee, HJ, Ryu, JS, Choi, IK, Park, KH, Kim, JS, Shin, SW, Chu, EK & Kim, YH 2008, 'Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer', Lung Cancer, vol. 61, no. 3, pp. 301-308. https://doi.org/10.1016/j.lungcan.2008.01.012
Sung, Jae Sook ; Han, S. G L ; Whang, Young M. ; Shin, Eun Soon ; Lee, Jae Won ; Lee, Hyo Jung ; Ryu, Jeong Seon ; Choi, In Keun ; Park, Kyong Hwa ; Kim, Jun Suk ; Shin, Sang Won ; Chu, Elizabeth K. ; Kim, Yeul Hong. / Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer. In: Lung Cancer. 2008 ; Vol. 61, No. 3. pp. 301-308.
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abstract = "The RASSF1 gene, a putative tumor suppressor gene located on human chromosome 3p21, has attracted a great deal of attention because of frequent allelic loss and gene silencing via promoter hypermethylation in a variety of human malignancies. To evaluate the role of RASSF1A gene in lung cancer risk, genotypes of the RASSF1A promoter region (-710 C > T and -392 T > C) were determined in 410 lung cancer patients and 410 normal subjects. Furthermore, to examine potential effects of the common haplotypes (C-C, T-T and C-T haplotypes) on RASSF1A transcription, luciferase reporter assays were performed in H2009 and H358 non-small cell lung cancer (NSCLC) cell lines. We found that ht2 C-T haplotype was associated with susceptibility to the risk of lung cancer in dominant (odds ratio (OR): 0.69; 95{\%} CI: 0.46-0.99) model. In particular, we found that C-T haplotype showed a decreased risk of lung cancer in males (codominant OR: 0.59; 95{\%} CI: 0.38-0.93 and dominant OR: 0.58; 95{\%} CI: 0.35-0.96) and in smokers (codominant OR: 0.58; 95{\%} CI: 0.36-0.93 and dominant OR: 0.56; 95{\%} CI: 0.33-0.96). Interestingly, C-T haplotype induced transcriptional activity by 50-60{\%} compared with other haplotypes in NSCLC cell lines. These results suggest that RASSF1A promoter polymorphisms affect RASSF1A expression, further contributing to the genetic susceptibility to lung cancer.",
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AU - Lee, Jae Won

AU - Lee, Hyo Jung

AU - Ryu, Jeong Seon

AU - Choi, In Keun

AU - Park, Kyong Hwa

AU - Kim, Jun Suk

AU - Shin, Sang Won

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N2 - The RASSF1 gene, a putative tumor suppressor gene located on human chromosome 3p21, has attracted a great deal of attention because of frequent allelic loss and gene silencing via promoter hypermethylation in a variety of human malignancies. To evaluate the role of RASSF1A gene in lung cancer risk, genotypes of the RASSF1A promoter region (-710 C > T and -392 T > C) were determined in 410 lung cancer patients and 410 normal subjects. Furthermore, to examine potential effects of the common haplotypes (C-C, T-T and C-T haplotypes) on RASSF1A transcription, luciferase reporter assays were performed in H2009 and H358 non-small cell lung cancer (NSCLC) cell lines. We found that ht2 C-T haplotype was associated with susceptibility to the risk of lung cancer in dominant (odds ratio (OR): 0.69; 95% CI: 0.46-0.99) model. In particular, we found that C-T haplotype showed a decreased risk of lung cancer in males (codominant OR: 0.59; 95% CI: 0.38-0.93 and dominant OR: 0.58; 95% CI: 0.35-0.96) and in smokers (codominant OR: 0.58; 95% CI: 0.36-0.93 and dominant OR: 0.56; 95% CI: 0.33-0.96). Interestingly, C-T haplotype induced transcriptional activity by 50-60% compared with other haplotypes in NSCLC cell lines. These results suggest that RASSF1A promoter polymorphisms affect RASSF1A expression, further contributing to the genetic susceptibility to lung cancer.

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