Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer

Bao Li Chang, S. Lilly Zheng, Sarah D. Isaacs, Aubrey R. Turner, Eugene R. Bleecker, Patrick Walsh, Deborah A. Meyers, William B Isaacs, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

BACKGROUND. The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS. Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS. Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS. Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalProstate
Volume56
Issue number1
DOIs
StatePublished - Jun 15 2003

Fingerprint

Single Nucleotide Polymorphism
Prostatic Neoplasms
Dihydrotestosterone
Cholestenone 5 alpha-Reductase
Alleles
Microsatellite Repeats
Androgens
Genes
Testosterone
Familial Prostate cancer
Case-Control Studies
Prostate
Enzymes
Population

Keywords

  • Association
  • Hereditary
  • Linkage
  • Prostate cancer
  • SRD5A2

ASJC Scopus subject areas

  • Urology

Cite this

Chang, B. L., Zheng, S. L., Isaacs, S. D., Turner, A. R., Bleecker, E. R., Walsh, P., ... Xu, J. (2003). Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer. Prostate, 56(1), 37-44. https://doi.org/10.1002/pros.10225

Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer. / Chang, Bao Li; Zheng, S. Lilly; Isaacs, Sarah D.; Turner, Aubrey R.; Bleecker, Eugene R.; Walsh, Patrick; Meyers, Deborah A.; Isaacs, William B; Xu, Jianfeng.

In: Prostate, Vol. 56, No. 1, 15.06.2003, p. 37-44.

Research output: Contribution to journalArticle

Chang, BL, Zheng, SL, Isaacs, SD, Turner, AR, Bleecker, ER, Walsh, P, Meyers, DA, Isaacs, WB & Xu, J 2003, 'Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer', Prostate, vol. 56, no. 1, pp. 37-44. https://doi.org/10.1002/pros.10225
Chang, Bao Li ; Zheng, S. Lilly ; Isaacs, Sarah D. ; Turner, Aubrey R. ; Bleecker, Eugene R. ; Walsh, Patrick ; Meyers, Deborah A. ; Isaacs, William B ; Xu, Jianfeng. / Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer. In: Prostate. 2003 ; Vol. 56, No. 1. pp. 37-44.
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abstract = "BACKGROUND. The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS. Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS. Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the {"}T{"} allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS. Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.",
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AU - Chang, Bao Li

AU - Zheng, S. Lilly

AU - Isaacs, Sarah D.

AU - Turner, Aubrey R.

AU - Bleecker, Eugene R.

AU - Walsh, Patrick

AU - Meyers, Deborah A.

AU - Isaacs, William B

AU - Xu, Jianfeng

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N2 - BACKGROUND. The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS. Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS. Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS. Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.

AB - BACKGROUND. The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS. Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS. Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS. Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.

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