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.
Highlights
Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally
This study aims to sequence RNase L single nucleotide polymorphisms (SNPs) in men with known cases of sporadic prostate cancer and correlate to the clinical aspects of the cancer
R462Q 9% of patients had the homozygous AA genotype (R462Q), which corresponds to the less efficient variant of the RNase L enzyme, while 52.2% were heterozygous for this SNP
Summary
Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally. The studied RNase L mutations including rs3738579 do not appear to have a significant impact on our patient population. RNase L is a gene found on the hereditary prostate cancer (HPC) locus of chromosome 1 that codes for a latent endoribonuclease. This enzyme participates in an interferon inducible RNA decay pathway that has a role in inflammation and cellular immunity against viral infection. The gene is 741 amino acids long with 8 exons and is roughly 13 kilobases It is converted from an inactive monomeric form to a potent dimeric structure by the action of a series of 2’ to 5’ linked oligodenylates, commonly known as 2 5 A. RNase L has been a candidate gene for prostate cancer researchers for a number of years and many variants including R462Q [1], E265X [1], M1I [2] and 471ΔAAAG [3] have been described
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