Analysis of the RNASEL gene in familial and sporadic prostate cancer

Liang Wang, Shannon K. McDonnell, David A. Elkins, Susan L Slager, Eric Christensen, Angela F. Marks, Julie M Cunningham, Brett J. Peterson, Steven J. Jacobsen, James R Cerhan, Michael L. Blute, Daniel J Schaid, Stephen N Thibodeau

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Abstract

The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (X2 trend test = 1.42; P = .23) or the Asp541 variant (X2 = 1.52; P = .22). However, significant differences were detected for the Arg462Gln genotypes (X2 = 5.20; P = .02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32-0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis ≤64 years) (P = .0008; OR = 0.29; 95% CI = 0.13-0.66), in node-negative patients (P = .01; OR = 0.48; 95% CI 0.27-0.84), patients with stage T1/T2 disease (P = .008; OR = 0.39; 95% CI 0.2-0.75), and patients with low-grade disease (P = .01; OR = 0.40; 95% CI 0.20-0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (X2 = 4.82; P = .03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalAmerican Journal of Human Genetics
Volume71
Issue number1
DOIs
StatePublished - 2002

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Genes
Odds Ratio
Confidence Intervals
Prostatic Neoplasms
Pyridinolcarbamate
Genotype
Familial Prostate cancer
Population Control
Germ-Line Mutation
Sequence Analysis
Electrophoresis
Age Groups
Chromosomes
Gels

ASJC Scopus subject areas

  • Genetics

Cite this

Analysis of the RNASEL gene in familial and sporadic prostate cancer. / Wang, Liang; McDonnell, Shannon K.; Elkins, David A.; Slager, Susan L; Christensen, Eric; Marks, Angela F.; Cunningham, Julie M; Peterson, Brett J.; Jacobsen, Steven J.; Cerhan, James R; Blute, Michael L.; Schaid, Daniel J; Thibodeau, Stephen N.

In: American Journal of Human Genetics, Vol. 71, No. 1, 2002, p. 116-123.

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 2002, 'Analysis of the RNASEL gene in familial and sporadic prostate cancer', American Journal of Human Genetics, vol. 71, no. 1, pp. 116-123. https://doi.org/10.1086/341281
Wang, Liang ; McDonnell, Shannon K. ; Elkins, David A. ; Slager, Susan L ; Christensen, Eric ; Marks, Angela F. ; Cunningham, Julie M ; Peterson, Brett J. ; Jacobsen, Steven J. ; Cerhan, James R ; Blute, Michael L. ; Schaid, Daniel J ; Thibodeau, Stephen N. / Analysis of the RNASEL gene in familial and sporadic prostate cancer. In: American Journal of Human Genetics. 2002 ; Vol. 71, No. 1. pp. 116-123.
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abstract = "The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (X2 trend test = 1.42; P = .23) or the Asp541 variant (X2 = 1.52; P = .22). However, significant differences were detected for the Arg462Gln genotypes (X2 = 5.20; P = .02; odds ratio [OR] = 0.54; 95{\%} confidence interval [CI] 0.32-0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis ≤64 years) (P = .0008; OR = 0.29; 95{\%} CI = 0.13-0.66), in node-negative patients (P = .01; OR = 0.48; 95{\%} CI 0.27-0.84), patients with stage T1/T2 disease (P = .008; OR = 0.39; 95{\%} CI 0.2-0.75), and patients with low-grade disease (P = .01; OR = 0.40; 95{\%} CI 0.20-0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (X2 = 4.82; P = .03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.",
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AU - Marks, Angela F.

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AU - Peterson, Brett J.

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N2 - The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (X2 trend test = 1.42; P = .23) or the Asp541 variant (X2 = 1.52; P = .22). However, significant differences were detected for the Arg462Gln genotypes (X2 = 5.20; P = .02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32-0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis ≤64 years) (P = .0008; OR = 0.29; 95% CI = 0.13-0.66), in node-negative patients (P = .01; OR = 0.48; 95% CI 0.27-0.84), patients with stage T1/T2 disease (P = .008; OR = 0.39; 95% CI 0.2-0.75), and patients with low-grade disease (P = .01; OR = 0.40; 95% CI 0.20-0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (X2 = 4.82; P = .03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.

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