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The Association Of XMRV With Chinese Prostate Cancer Patients

Posted on:2013-10-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:D WangFull Text:PDF
GTID:1224330395973720Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Prostate cancer is a multi-factorial complex disease and the mutation of R462Q genotype of the antiviral enzyme RNASEL has been identified to be involved in the development of prostate cancer. A novel virus named xenotropic murine leukemia virus-related virus (XMRV) was discovered by Urishman, et al. in2006in Caucasian prostate cancer patients. XMRV is the first y retrovirus which could infect human beings. However, some conflicting findings of the link between XMRV and prostate cancer have been reported by different laboratories or in different regions, some studies also indicated murine-originated contamination exited in XMRV detection. Considering the potential great medical and social relevance of this discovery, we therefore investigated the prevalence of XMRV in Chinese prostate cancer patients and healthy blood donors, and also inspected the association of R462Q with prostate cancer in Chinese Han nationality.Methods:1. R462Q genotype was determined by PCR and conventional Sanger sequencing method from125prostate cancer patients and240Han healthy blood donors.2.170prostate cancer patients and392healthy blood donors were tested for XMRV by PCR. The whole virus genome was also amplified with different primer sets. qPCR were taken to detect the virus copies. Western blot and plasma coculture with LNCaP were performed targeting XMRV env protein and infectious XMRV detection, respectively.3. mtDNA PCR was performed to screen for mouse DNA contamination. Results:1. According to our study, the frequency of RNase L R462Q variant was implicated in up to20.2%in healthy blood donors whereas with a frequency of17.2%of prostate cancer cases in Chinese Han nationality.2. Instead of XMRV, diverse mERVs’ sequences were detected in5blood donors and5prostate cancer cases by nested-PCR detection whereas no whole virus genome was detected; qPCR showed a low virus copies in positive samples; Taken together with failure to amplify the whole genome, no virus protein and infectious virus were detected by western blot and cocultured of plasma-LNCaP.3.2positive samples of healthy blood donors were proved to be mouse genome contamination by mtDNA PCR.Conclusion:Our study indicated that there is no significant association between R462Q genotype and prostate cancer in Chinese Han nationality and mouse contamination exited in XMRV detection.
Keywords/Search Tags:XMRV, R462Q, prostate cancer, blood donor, contamination
PDF Full Text Request
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