PT - JOURNAL ARTICLE AU - Leng, Shuguang AU - Bernauer, Amanda AU - Stidley, Christine AU - Picchi, Maria AU - Burki, Elizabeth AU - Gilliland, Frank AU - Crowell, Richard AU - Byers, Timothy AU - Belinsky, Steven TI - Abstract #104: Functional SNPs in microRNAs and genes involved in epithelial to mesenchymal transition and risk for lung cancer and cancer survival DP - 2009 May 01 TA - Cancer Research PG - 104--104 VI - 69 IP - 9 Supplement 4099 - http://cancerres.aacrjournals.org/content/69/9_Supplement/104.short 4100 - http://cancerres.aacrjournals.org/content/69/9_Supplement/104.full SO - Cancer Res2009 May 01; 69 AB - AACR Annual Meeting-- Apr 18-22, 2009; Denver, COCurrently, over 700 microRNAs have been identified and are predicted to regulate 20-30% of all human genes with an average of 200 predicted targets per microRNA. Because each microRNA can regulate hundreds of genes simultaneously, dysfunction of a microRNA could have a major impact in cancer etiology. Polymorphisms in pre-microRNAs (before processing) and microRNA targets can alter processing, expression, and binding to target mRNA to impact carcinogenesis. Recent studies have shown that reduced expression of specific microRNAs may induce the epithelial to mesenchymal transition (EMT), a key developmental program that is activated during cancer invasion and metastasis. A study was initiated to determine whether sequence variations are present in promoter and coding regions of micro-RNAs and the 3'UTR of genes causal for EMT. The genomic region encompassing the promoter region and coding sequence of six microRNAs (has-mir-141, 429, and 200a, b, and c and has-mir-205) was amplified from DNA isolated from lymphocytes from 20 cases of lung cancer matched to 20 controls by age, gender, and smoking status. The 3'UTR of ZEB1 and ZEB2, and the promoter of E-cadherin were also amplified. Direct sequencing of PCR products identified a total of 12 SNPs, four deletions, and one repeat with frequencies > 0.05, six of which are newly discovered and five are reported, but not characterized. We are currently assessing whether identified sequence changes in the promoter regions and 3'UTRs affect transcription of the microRNA and expression of the gene, respectively. The association of the identified \#8220;functional\#8221; SNPs to lung cancer will be determined in the New Mexico and Colorado lung cancer cohorts by using the Illumina Veracode assay. (Supported by U01 CA097356 and the State of New Mexico as a direct appropriation from the Tobacco Settlement Fund)Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 104.