Abstract 1848: Evaluation of the frequency of RNASE L in 462 and 541 variants in Iranian prostate cancer patients

Abstract

Abstract Introduction: Several genetic loci are suspected to be involved in prostate cancer, including the hereditary prostate cancer. RNASEL regulates cell proliferation and apoptosis through the IFN-regulated 2-5A pathway that mediates anti proliferative activities and has been suggested to be a candidate tumor suppressor gene. There are numerous nucleotide variants identified in the RNASEL gene. The two most commonly found variants in the U.S. non-Hispanic Caucasian population are the non-synonymous variants: 1385 G>A; Arg462Gln; and 1623T>G; Asp 541 Glu has been reported. The Arg 462 Gln variant reduces the ability of the cell to cause apoptosis in response to activation by 2-5 (A) and also has three times less enzymatic activity than normal, whereas the Asp 541 Glu variant has no known effect on RNASEL protein function. There continues to be much debate over whether these common variants increase the risk of prostate cancer. It has been also reported that the Arg 462 Gln AA genotype associated with both increased prostate cancer in U.S. Caucasian sample groups and decreased prostate cancer risk in Caucasian and Japanese sample groups Moreover, the Asp 541 Glu variant within RNASEL has been reported that the GG and TT genotypes were associated with an increased risk for prostate cancer in Japanese and European-American samples, respectively. On the other hand, a significant negative association of the TT genotype with prostate cancer in Swedish Caucasian samples has been reported .However; the role of these common mutations is debatable. The aim of this study was to investigate the role of common variants of RNASE L gene; Arg 462 Gln and Asp 541 Glu in Iranian men with prostate cancer. Patients and Methods:Blocks of paraffin-embedded tissue from 46 patients with adenoma carcinoma prostate cancer and 50 patients with hyperplasia prostate tissue and also fifty healthy blood controls with PSA<4 was enrolled in this current research study. ARMS-PCR amplification was performed with specific primers. Results and Conclusions: This is the first study that investigates the association of prostate cancer risk with RNASEL variants in Iranian prostate cancer patients. Our result indicated that the frequency of the AA, GG and AG genotypes in the RNASEL 462 SNP in Tumors were 30%, 13.3% and 56.66% respectively, in hyperplasia was 30.3% ,15.15% and 54.54% respectively and in controls was 26%, 14% and 60% respectively .The frequency of the TT, GG and TG genotypes in the RNASEL 541 SNP in Tumors were 3%, 0 % and 93.47% respectively, in hyperplasia were 10 %,0% and 90% and in blood controls were 8%, 0% and 92% respectively. Our finding indicated that these variations were not a significant association with prostate cancer risk in Iranian patients and the other variations of this gene maybe involve in Iranian prostate cancer patients. Note: This abstract was not presented at the meeting. Citation Format: Sirweh Molla, Massoud Ghaffarpour, Somayeh Saeeda, Seyed Werya Hossieni, Sina Mirzaahmadi, Mohammad Reza Rahmany. Evaluation of the frequency of RNASE L in 462 and 541 variants in Iranian prostate cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1848. doi:10.1158/1538-7445.AM2014-1848