RNase L Variants Do Not Appear to Impact on Clinical Features of Sporadic Prostate Cancer Patients
- 1 Institute of Molecular Medicine, Trinity College, Dublin, Ireland
- 2 Institute of Molecular Medicine, Trinity College, Dublin, Ireland
- 3 Department of Urology, St. James Hospital, Dublin, Ireland
Abstract
Introduction : Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally. Mutations of RNase L, an enzyme involved in inflammatory and immunological pathways, have been speculated to predispose to cancer. This study assesses three different mutations of the RNase L gene in Irish prostate cancer patients, including one linked with general cancer susceptibility never investigated before in prostate cancer (rs3738579), and reports on links with aggressive cancer. Methods : 134 patients had their RNase L mutation status determined by polymerase chain reaction (PCR) of serum DNA. Complementary clinical details for each patient are statistically analysed. Results : No link to age of diagnosis, high grade disease or prostate specific antigen (PSA) level at diagnosis was demonstrated with any of the studied single nucleotide polymorphisms (SNP). The SNP variation was consistent with that of published international series. Conclusion : SNP genotypic frequencies in Ireland are consistent with international findings. The studied RNase L mutations including rs3738579 do not appear to have a significant impact on our patient population.
- A. Rokman, T. Ikonen, E. H. Seppala, N. Nupponen, V. Autio, N. Mononen, J. Bailey-Wilson, J. Trent, J. Carpten, M. P. Matikainen, P. A. Koivisto, T. L. Tammela, O. P. Kallioniemi and J. Schleutker, “Germline Alterations of the RNASEL Gene, a Candidate HPC1 Gene at 1q25, in Patients and Families with Prostate Cancer,” The American Journal of Human Genetics, Vol. 70, No. 5, 2002, pp. 1299-1304. http://dx.doi.org/10.1086/340450
- J. Carpten, N. Nupponen, S. Isaacs, R. Sood, C. Robbins, J. Xu, M. Faruque, T. Moses, C. Ewing, E. Gillanders, P. Hu, P. Bujnovszky, I. Makalowska, A. Baffoe-Bonnie, D. Faith, J. Smith, D. Stephan, K. Wiley, M. Brownstein, D. Gildea, B. Kelly, R. Jenkins, G. Hostetter, M. Matikainen, J. Schleutker, K. Klinger, T. Connors, Y. Xiang, Z. Wang, A. De Marzo, N. Papadopoulos, O. P. Kallioniemi, R. Burk, D. Meyers, H. Gronberg, P. Meltzer, R. Silverman, J. Bailey-Wilson, P. Walsh, W. Isaacs and J. Trent, “Germline Mutations in the Ribonuclease L Gene in Families Showing Linkage with HPC1,” Nature Genetics, Vol. 30, No. 2, 2002, pp. 181-184. http://dx.doi.org/10.1038/ng823
- A. Orr-Urtreger, A. Bar-Shira, D. Bercovich, N. Matarasso, U. Rozovsky, S. Rosner, S. Soloviov, G. Rennert, L. Kadouri, A. Hubert, H. Rennert and H. Matzkin, “RNASEL Mutation Screening and Association Study in Ashkenazi and Non-Ashkenazi Prostate Cancer Patients,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 15, No. 3, 2006, pp. 474-479. http://dx.doi.org/10.1158/1055-9965.EPI-05-0606
- Y. Xiang, Z. Wang, J. Murakami, S. Plummer, E. A. Klein, J. D. Carpten, J. M. Trent, W. B. Isaacs, G. Casey and R. H. Silverman, “Effects of RNase L Mutations Associated with Prostate Cancer on Apoptosis Induced by 2’,5’-Oligoadenylates,” Cancer Research, Vol. 63, No. 20, 2003, pp. 6795-6801.
- L. Wang, S. K. McDonnell, D. A. Elkins, S. L. Slager, E. Christensen, A. F. Marks, J. M. Cunningham, B. J. Peterson, S. J. Jacobsen, J. R. Cerhan, M. L. Blute, D. J. Schaid and S. N. Thibodeau, “No Association of Germline Alteration of MSR1 with Prostate Cancer Risk,” Nature Genetics, Vol. 35, 2003, pp. 128-129. http://dx.doi.org/10.1038/ng1239
- G. Casey, P. J. Neville, S. J. Plummer, Y. Xiang, L. M. Krumroy, E. A. Klein, W. J. Catalona, N. Nupponen, J. D. Carpten, J. M. Trent, R. H. Silverman and J. S. Witte, “RNASEL Arg462Gln Variant Is Implicated in up to 13% of Prostate Cancer Cases,” Nature Genetics, Vol. 32, No. 4, 2002, pp. 581-583. http://dx.doi.org/10.1038/ng1021
- F. Wiklund, B. A. Jonsson, A. J. Brookes, L. Stromqvist, J. Adolfsson, M. Emanuelsson, H. O. Adami, K. Augustsson-Balter and H. Gronberg, “Genetic Analysis of the RNASEL Gene in Hereditary, Familial, and Sporadic Prostate Cancer,” Clinical Cancer Research, Vol. 10, No. 21, 2004, pp. 7150-7156. http://dx.doi.org/10.1158/1078-0432.CCR-04-0982