Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population

Ilir Agalliu, Suzanne M. Leanza, Lorie Smith, Jeffrey M. Trent, John D. Carpten, Joan E. Bailey-Wilson, Robert D. Burk

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain. METHODS Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P<0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors. CONCLUSIONS Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity. Prostate 70: 1716-1727, 2010.

Original languageEnglish (US)
Pages (from-to)1716-1727
Number of pages12
JournalProstate
Volume70
Issue number15
DOIs
StatePublished - Nov 1 2010

Fingerprint

Prostatic Neoplasms
Odds Ratio
Population
Alleles
Logistic Models
Genotype
Neoplasms
Mutation
Proteins
Neoplasm Grading
Microsatellite Repeats
Genes
Single Nucleotide Polymorphism
Prostate
Confidence Intervals
Familial Prostate cancer

Keywords

  • Founder population
  • Genetic susceptibility
  • HPCX
  • Prostate cancer
  • RNASEL

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Agalliu, I., Leanza, S. M., Smith, L., Trent, J. M., Carpten, J. D., Bailey-Wilson, J. E., & Burk, R. D. (2010). Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population. Prostate, 70(15), 1716-1727. https://doi.org/10.1002/pros.21207

Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population. / Agalliu, Ilir; Leanza, Suzanne M.; Smith, Lorie; Trent, Jeffrey M.; Carpten, John D.; Bailey-Wilson, Joan E.; Burk, Robert D.

In: Prostate, Vol. 70, No. 15, 01.11.2010, p. 1716-1727.

Research output: Contribution to journalArticle

Agalliu, I, Leanza, SM, Smith, L, Trent, JM, Carpten, JD, Bailey-Wilson, JE & Burk, RD 2010, 'Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population', Prostate, vol. 70, no. 15, pp. 1716-1727. https://doi.org/10.1002/pros.21207
Agalliu I, Leanza SM, Smith L, Trent JM, Carpten JD, Bailey-Wilson JE et al. Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population. Prostate. 2010 Nov 1;70(15):1716-1727. https://doi.org/10.1002/pros.21207
Agalliu, Ilir ; Leanza, Suzanne M. ; Smith, Lorie ; Trent, Jeffrey M. ; Carpten, John D. ; Bailey-Wilson, Joan E. ; Burk, Robert D. / Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population. In: Prostate. 2010 ; Vol. 70, No. 15. pp. 1716-1727.
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abstract = "BACKGROUND Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain. METHODS Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95{\%} confidence intervals (CIs) were estimated using logistic regression models. RESULTS There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P<0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors. CONCLUSIONS Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity. Prostate 70: 1716-1727, 2010.",
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T1 - Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population

AU - Agalliu, Ilir

AU - Leanza, Suzanne M.

AU - Smith, Lorie

AU - Trent, Jeffrey M.

AU - Carpten, John D.

AU - Bailey-Wilson, Joan E.

AU - Burk, Robert D.

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N2 - BACKGROUND Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain. METHODS Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P<0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors. CONCLUSIONS Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity. Prostate 70: 1716-1727, 2010.

AB - BACKGROUND Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain. METHODS Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P<0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors. CONCLUSIONS Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity. Prostate 70: 1716-1727, 2010.

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KW - Prostate cancer

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