RNASEL is the most likely candidate prostate cancer susceptibility gene of the HPC1 locus at 1q23. It encodes a constitutively expressed latent 2'-5’-oligoadenylate-dependent ribonuclease that mediates the antiviral and pro-apoptotic activities of the interferon-inducible 2-5A system. In single high risk families rare inactivating mutations have been reported and association studies of sporadic prostate cancer with the common R462Q polymorphism resulted in variable findings in different populations. To our knowledge, this putative low-penetrance allele has not been previously analyzed in the Italian population. We collected DNA samples of 192 prostate cancer patients attending four participating Urologic Units and 218 controls, with the aim to evaluate the frequency of R462Q in our population and detect possible differences between sporadic and familial cases, useful to plan a larger prospective study on this and other SNPs. Genotyping was done by PCR-DHPLC. Genotype frequencies (%) in controls were: RR 43.6, RQ 42.2, QQ 14.2 vs 31.2, 51.6 and 17.2 in patients. Allele Q was significantly more frequent in patients (69%) vs. controls (56% p0.01), and RR have an average age of onset three years later than patients carrying Q in single or double dose. Early detection of prostate cancer is currently based on PSA testing, which as a screening strategy is debated. Identification of new predisposing genes might contribute both to a better understanding of the underlying molecular mechanisms, and also open new ways for defining the individual risks, a difficult challenge if prostate cancer susceptibility depends on several low-risk rather than few high-risk genes.

RNASEL R462Q is significantly associated with Prostate Cancer in the Italian population

VAN DUIST, Marjan Maria;GIACHINO, Daniela Francesca;ZITELLA, Andrea;CRACCO, CECILIA MARIA;SCARPA, Roberto Mario;FONTANA, Dario;TIZZANI, Alessandro;DE MARCHI, Mario
2005-01-01

Abstract

RNASEL is the most likely candidate prostate cancer susceptibility gene of the HPC1 locus at 1q23. It encodes a constitutively expressed latent 2'-5’-oligoadenylate-dependent ribonuclease that mediates the antiviral and pro-apoptotic activities of the interferon-inducible 2-5A system. In single high risk families rare inactivating mutations have been reported and association studies of sporadic prostate cancer with the common R462Q polymorphism resulted in variable findings in different populations. To our knowledge, this putative low-penetrance allele has not been previously analyzed in the Italian population. We collected DNA samples of 192 prostate cancer patients attending four participating Urologic Units and 218 controls, with the aim to evaluate the frequency of R462Q in our population and detect possible differences between sporadic and familial cases, useful to plan a larger prospective study on this and other SNPs. Genotyping was done by PCR-DHPLC. Genotype frequencies (%) in controls were: RR 43.6, RQ 42.2, QQ 14.2 vs 31.2, 51.6 and 17.2 in patients. Allele Q was significantly more frequent in patients (69%) vs. controls (56% p0.01), and RR have an average age of onset three years later than patients carrying Q in single or double dose. Early detection of prostate cancer is currently based on PSA testing, which as a screening strategy is debated. Identification of new predisposing genes might contribute both to a better understanding of the underlying molecular mechanisms, and also open new ways for defining the individual risks, a difficult challenge if prostate cancer susceptibility depends on several low-risk rather than few high-risk genes.
EUROPEAN HUMAN GENETICS CONFERENCE 2005
PRAGA
7-10 MAGGIO 2005
13
199
200
M. M. van Duist; D. Giachino; A. Zitella; P. De Stefanis; M. E. Graziano; C. Cracco; R. Scarpa; U. Ferrando; D. Fontana; A. Tizzani; M. De Marchi
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/72773
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact