Role of HPC2/ELAC2 in hereditary prostate cancer

L. Wang, S. K. McDonnell, D. A. Elkins, Susan L Slager, E. Christensen, A. F. Marks, Julie M Cunningham, B. J. Peterson, S. J. Jacobsen, James R Cerhan, M. L. Blute, Daniel J Schaid, Stephen N Thibodeau

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Abstract

The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sensitive gel electrophoresis, followed by direct sequence analysis. The minimum criteria for our families with HPC was the presence of 3 affected men with prostate cancer. A total of 23 variants were identified, including 13 intronic and 10 exonic changes. Of the 10 exonic changes, 1 truncating mutation was identified, a Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected men in a single family. The remaining nine alterations included five missense, three silent, and one variant in the 3′ untranslated region. To additionally test for potential associations of polymorphic variants and increased risk for disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446 prostate cancer patients from 164 families with HPC and 502 population-based controls. The frequency of the Leu217 variant was similar for patients (32.3%) and controls (31.8%), as was the frequency of the Thr541 variant (5.4% among patients versus 5.2% among controls). In contrast to previous reports, we found no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95% confidence interval, 0.57-1.89). Overall, our results did not reveal any association between these two common polymorphisms and the risk for HPC. The finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role in genetic susceptibility to prostate cancer. However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC.

Original languageEnglish (US)
Pages (from-to)6494-6499
Number of pages6
JournalCancer Research
Volume61
Issue number17
StatePublished - Aug 1 2001

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Prostatic Neoplasms
Germ-Line Mutation
Nonsense Codon
Genetic Predisposition to Disease
Genes
Population Control
Familial Prostate cancer
3' Untranslated Regions
Sequence Analysis
Electrophoresis
Chromosomes
Gels
Odds Ratio
Confidence Intervals
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wang, L., McDonnell, S. K., Elkins, D. A., Slager, S. L., Christensen, E., Marks, A. F., ... Thibodeau, S. N. (2001). Role of HPC2/ELAC2 in hereditary prostate cancer. Cancer Research, 61(17), 6494-6499.

Role of HPC2/ELAC2 in hereditary prostate cancer. / Wang, L.; McDonnell, S. K.; Elkins, D. A.; Slager, Susan L; Christensen, E.; Marks, A. F.; Cunningham, Julie M; Peterson, B. J.; Jacobsen, S. J.; Cerhan, James R; Blute, M. L.; Schaid, Daniel J; Thibodeau, Stephen N.

In: Cancer Research, Vol. 61, No. 17, 01.08.2001, p. 6494-6499.

Research output: Contribution to journalArticle

Wang, L, McDonnell, SK, Elkins, DA, Slager, SL, Christensen, E, Marks, AF, Cunningham, JM, Peterson, BJ, Jacobsen, SJ, Cerhan, JR, Blute, ML, Schaid, DJ & Thibodeau, SN 2001, 'Role of HPC2/ELAC2 in hereditary prostate cancer', Cancer Research, vol. 61, no. 17, pp. 6494-6499.
Wang L, McDonnell SK, Elkins DA, Slager SL, Christensen E, Marks AF et al. Role of HPC2/ELAC2 in hereditary prostate cancer. Cancer Research. 2001 Aug 1;61(17):6494-6499.
Wang, L. ; McDonnell, S. K. ; Elkins, D. A. ; Slager, Susan L ; Christensen, E. ; Marks, A. F. ; Cunningham, Julie M ; Peterson, B. J. ; Jacobsen, S. J. ; Cerhan, James R ; Blute, M. L. ; Schaid, Daniel J ; Thibodeau, Stephen N. / Role of HPC2/ELAC2 in hereditary prostate cancer. In: Cancer Research. 2001 ; Vol. 61, No. 17. pp. 6494-6499.
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abstract = "The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sensitive gel electrophoresis, followed by direct sequence analysis. The minimum criteria for our families with HPC was the presence of 3 affected men with prostate cancer. A total of 23 variants were identified, including 13 intronic and 10 exonic changes. Of the 10 exonic changes, 1 truncating mutation was identified, a Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected men in a single family. The remaining nine alterations included five missense, three silent, and one variant in the 3′ untranslated region. To additionally test for potential associations of polymorphic variants and increased risk for disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446 prostate cancer patients from 164 families with HPC and 502 population-based controls. The frequency of the Leu217 variant was similar for patients (32.3{\%}) and controls (31.8{\%}), as was the frequency of the Thr541 variant (5.4{\%} among patients versus 5.2{\%} among controls). In contrast to previous reports, we found no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95{\%} confidence interval, 0.57-1.89). Overall, our results did not reveal any association between these two common polymorphisms and the risk for HPC. The finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role in genetic susceptibility to prostate cancer. However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC.",
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AU - Marks, A. F.

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