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

Jae Sook Sung, Sle Gi Lo Han, Young Mi 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 journalArticlepeer-review

    10 Citations (Scopus)

    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 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

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