title: 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 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 -392T>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.
authors.affiliation: Department of Internal Medicine, Division of Brain, Korea 21 Project for Biomedical Science, Seoul, Republic of Korea.
authors.forename: Jae Sook
authors.initials: JS
authors.lastname: Sung
authors.forename: Sle Gi Lo
authors.initials: SG
authors.lastname: Han
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Whang
authors.forename: Eun Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jeong-Seon
authors.initials: JS
authors.lastname: Ryu
authors.forename: In Keun
authors.initials: IK
authors.lastname: Choi
authors.forename: Kyong Hwa
authors.initials: KH
authors.lastname: Park
authors.forename: Jun Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Shin
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Chu
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
mesh_terms: D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins