Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility

Bao Li Chang, Siqun L. Zheng, Gregory A. Hawkins, Sarah D. Isaacs, Kathy E. Wiley, Aubrey Turner, John D. Carpten, Eugene R. Bleecker, Patrick Walsh, Jeffrey M. Trent, Deborah A. Meyers, William B Isaacs, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

3β-hydroxysteroid dehydrogenases (HSD3Bs), encoded by the HSD3B gene family at 1p13, have long been hypothesized to have a major role in prostate cancer susceptibility. The recent reports of a prostate cancer linkage at 1p13 provided additional evidence that HSD3B genes may be prostate cancer susceptibility genes. To evaluate the possible role of HSD3B genes in prostate cancer, we screened a panel of DNA samples collected from 96 men with or without prostate cancer for sequence variants in the putative promoter region, exons, exon-intron junctions, and 3′-untranslated region of HSD3B1 and HSD3B2 genes by direct sequencing. Eleven single nucleotide polymorphisms (SNPs) were identified, four of which, including a missense change (B1-N367T), were informative. These four SNPs were further genotyped in a total of 159 hereditary prostate cancer probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Although a weak association between prostate cancer risk and a missense SNP (B1-N367T) was found, stronger evidence for association was found when the joint effect of the two genes was considered. Men with the variant genotypes at either B1-N367T or B2-c7519g had a significantly higher risk to develop prostate cancer, especially the hereditary type of prostate cancer. Most importantly, the subset of hereditary prostate cancer probands, whose families provided evidence for linkage at 1p13, predominantly contributed to the observed association. Additional studies are warranted to confirm these findings.

Original languageEnglish (US)
Pages (from-to)1784-1789
Number of pages6
JournalCancer Research
Volume62
Issue number6
StatePublished - Mar 15 2002

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Prostatic Neoplasms
Genes
Single Nucleotide Polymorphism
Exons
3-Hydroxysteroid Dehydrogenases
Familial Prostate cancer
3 beta-hydroxysteroid dehydrogenase type II
Neoplasm Genes
3' Untranslated Regions
Genetic Promoter Regions
Introns
Genotype
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chang, B. L., Zheng, S. L., Hawkins, G. A., Isaacs, S. D., Wiley, K. E., Turner, A., ... Xu, J. (2002). Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility. Cancer Research, 62(6), 1784-1789.

Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility. / Chang, Bao Li; Zheng, Siqun L.; Hawkins, Gregory A.; Isaacs, Sarah D.; Wiley, Kathy E.; Turner, Aubrey; Carpten, John D.; Bleecker, Eugene R.; Walsh, Patrick; Trent, Jeffrey M.; Meyers, Deborah A.; Isaacs, William B; Xu, Jianfeng.

In: Cancer Research, Vol. 62, No. 6, 15.03.2002, p. 1784-1789.

Research output: Contribution to journalArticle

Chang, BL, Zheng, SL, Hawkins, GA, Isaacs, SD, Wiley, KE, Turner, A, Carpten, JD, Bleecker, ER, Walsh, P, Trent, JM, Meyers, DA, Isaacs, WB & Xu, J 2002, 'Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility', Cancer Research, vol. 62, no. 6, pp. 1784-1789.
Chang BL, Zheng SL, Hawkins GA, Isaacs SD, Wiley KE, Turner A et al. Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility. Cancer Research. 2002 Mar 15;62(6):1784-1789.
Chang, Bao Li ; Zheng, Siqun L. ; Hawkins, Gregory A. ; Isaacs, Sarah D. ; Wiley, Kathy E. ; Turner, Aubrey ; Carpten, John D. ; Bleecker, Eugene R. ; Walsh, Patrick ; Trent, Jeffrey M. ; Meyers, Deborah A. ; Isaacs, William B ; Xu, Jianfeng. / Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility. In: Cancer Research. 2002 ; Vol. 62, No. 6. pp. 1784-1789.
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abstract = "3β-hydroxysteroid dehydrogenases (HSD3Bs), encoded by the HSD3B gene family at 1p13, have long been hypothesized to have a major role in prostate cancer susceptibility. The recent reports of a prostate cancer linkage at 1p13 provided additional evidence that HSD3B genes may be prostate cancer susceptibility genes. To evaluate the possible role of HSD3B genes in prostate cancer, we screened a panel of DNA samples collected from 96 men with or without prostate cancer for sequence variants in the putative promoter region, exons, exon-intron junctions, and 3′-untranslated region of HSD3B1 and HSD3B2 genes by direct sequencing. Eleven single nucleotide polymorphisms (SNPs) were identified, four of which, including a missense change (B1-N367T), were informative. These four SNPs were further genotyped in a total of 159 hereditary prostate cancer probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Although a weak association between prostate cancer risk and a missense SNP (B1-N367T) was found, stronger evidence for association was found when the joint effect of the two genes was considered. Men with the variant genotypes at either B1-N367T or B2-c7519g had a significantly higher risk to develop prostate cancer, especially the hereditary type of prostate cancer. Most importantly, the subset of hereditary prostate cancer probands, whose families provided evidence for linkage at 1p13, predominantly contributed to the observed association. Additional studies are warranted to confirm these findings.",
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AU - Turner, Aubrey

AU - Carpten, John D.

AU - Bleecker, Eugene R.

AU - Walsh, Patrick

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