Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer.
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.
Sung
Jae Sook
JS
Department of Internal Medicine, Division of Brain, Korea 21 Project for Biomedical Science, Seoul, Republic of Korea.
Han
Sle Gi Lo
SG
Whang
Young Mi
YM
Shin
Eun Soon
ES
Lee
Jae Won
JW
Lee
Hyo Jung
HJ
Ryu
Jeong-Seon
JS
Choi
In Keun
IK
Park
Kyong Hwa
KH
Kim
Jun Suk
JS
Shin
Sang Won
SW
Chu
Elizabeth K
EK
Kim
Yeul Hong
YH
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
D025521:Tumor Suppressor Proteins