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 language | English |
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Pages (from-to) | 301-308 |
Number of pages | 8 |
Journal | Lung Cancer |
Volume | 61 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2008 Sept |
Bibliographical note
Funding Information:We thank Young Lim, Dong-Hoon Shin, Choon-Sik Park and Yangsoo Jang for sample collection and provision. This study was supported by grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A010250), Jae Won Lee and Hyo Jung Lee was supported by Korea Science and Engineering Foundation Grant (R14-2003-002-01002-0).
Keywords
- Haplotype
- Lung cancer
- RASSF1A
- Single nucleotide polymorphism (SNP)
- Transcriptional activity
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
- Cancer Research