Association of polymorphisms in TGFB1 and prostate cancer prognosis

Timothy C. Brand, Carlos Bermejo, Edith Canby-Hagino, Dean A. Troyer, Jacques Baillargeon, Ian M. Thompson, Robin J. Leach, Susan L. Naylor

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. Materials and Methods: This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. Results: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). Conclusions: We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

Original languageEnglish (US)
Pages (from-to)754-758
Number of pages5
JournalJournal of Urology
Volume179
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Prostatic Neoplasms
Genotype
Ethnic Groups
Single Nucleotide Polymorphism
Logistic Models
Digital Rectal Examination
Chi-Square Distribution
Prostate-Specific Antigen
Case-Control Studies
Volunteers
Neoplasms
Biopsy
Recurrence

Keywords

  • Polymorphism, single nucleotide
  • Prostate
  • Prostatic neoplasms
  • Risk factors
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Urology
  • Medicine(all)

Cite this

Brand, T. C., Bermejo, C., Canby-Hagino, E., Troyer, D. A., Baillargeon, J., Thompson, I. M., ... Naylor, S. L. (2008). Association of polymorphisms in TGFB1 and prostate cancer prognosis. Journal of Urology, 179(2), 754-758. https://doi.org/10.1016/j.juro.2007.09.020

Association of polymorphisms in TGFB1 and prostate cancer prognosis. / Brand, Timothy C.; Bermejo, Carlos; Canby-Hagino, Edith; Troyer, Dean A.; Baillargeon, Jacques; Thompson, Ian M.; Leach, Robin J.; Naylor, Susan L.

In: Journal of Urology, Vol. 179, No. 2, 02.2008, p. 754-758.

Research output: Contribution to journalArticle

Brand, TC, Bermejo, C, Canby-Hagino, E, Troyer, DA, Baillargeon, J, Thompson, IM, Leach, RJ & Naylor, SL 2008, 'Association of polymorphisms in TGFB1 and prostate cancer prognosis', Journal of Urology, vol. 179, no. 2, pp. 754-758. https://doi.org/10.1016/j.juro.2007.09.020
Brand TC, Bermejo C, Canby-Hagino E, Troyer DA, Baillargeon J, Thompson IM et al. Association of polymorphisms in TGFB1 and prostate cancer prognosis. Journal of Urology. 2008 Feb;179(2):754-758. https://doi.org/10.1016/j.juro.2007.09.020
Brand, Timothy C. ; Bermejo, Carlos ; Canby-Hagino, Edith ; Troyer, Dean A. ; Baillargeon, Jacques ; Thompson, Ian M. ; Leach, Robin J. ; Naylor, Susan L. / Association of polymorphisms in TGFB1 and prostate cancer prognosis. In: Journal of Urology. 2008 ; Vol. 179, No. 2. pp. 754-758.
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abstract = "Purpose: Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. Materials and Methods: This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95{\%} CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. Results: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95{\%} CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95{\%} CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95{\%} CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). Conclusions: We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.",
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AU - Brand, Timothy C.

AU - Bermejo, Carlos

AU - Canby-Hagino, Edith

AU - Troyer, Dean A.

AU - Baillargeon, Jacques

AU - Thompson, Ian M.

AU - Leach, Robin J.

AU - Naylor, Susan L.

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N2 - Purpose: Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. Materials and Methods: This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. Results: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). Conclusions: We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

AB - Purpose: Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. Materials and Methods: This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. Results: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). Conclusions: We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

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KW - Prostatic neoplasms

KW - Risk factors

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