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

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 toss 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 RASSF1 A transcription, luciferase reporter assays were performed in H2009 and H358 non-small. cell lung cancer (NSCLC) cell tines. 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 mates (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. (c) 2008 Elsevier Ireland Ltd. All rights reserved.