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

doi:10.1016/j.juro.2007.09.020

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 journal › Article › peer-review

13 Scopus citations

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 language	English (US)
Pages (from-to)	754-758
Number of pages	5
Journal	Journal of Urology
Volume	179
Issue number	2
DOIs	https://doi.org/10.1016/j.juro.2007.09.020
State	Published - Feb 2008

Keywords

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

ASJC Scopus subject areas

Urology

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10.1016/j.juro.2007.09.020

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@article{929026e0ae9642efad82d66019ed9318,

title = "Association of polymorphisms in TGFB1 and prostate cancer prognosis",

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.",

keywords = "Polymorphism, single nucleotide, Prostate, Prostatic neoplasms, Risk factors, Transforming growth factor beta",

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

note = "Funding Information: Supported by San Antonio Center of Biomarkers of Risk for Prostate Cancer Grant U01 CA86402, San Antonio Cancer Center Institute Grant P30 CA54174, American Cancer Society Grant TURSG-03-152-01-CCE entitled The Role of Genetic Variation in Prostate Cancer Among Hispanics and Blacks, and Department of Defense Grant W81XWH-05-1-0203. ",

year = "2008",

month = feb,

doi = "10.1016/j.juro.2007.09.020",

language = "English (US)",

volume = "179",

pages = "754--758",

journal = "Journal of Urology",

issn = "0022-5347",

publisher = "Elsevier Inc.",

number = "2",

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TY - JOUR

T1 - Association of polymorphisms in TGFB1 and prostate cancer prognosis

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.

N1 - Funding Information: Supported by San Antonio Center of Biomarkers of Risk for Prostate Cancer Grant U01 CA86402, San Antonio Cancer Center Institute Grant P30 CA54174, American Cancer Society Grant TURSG-03-152-01-CCE entitled The Role of Genetic Variation in Prostate Cancer Among Hispanics and Blacks, and Department of Defense Grant W81XWH-05-1-0203.

PY - 2008/2

Y1 - 2008/2

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.

KW - Polymorphism, single nucleotide

KW - Prostate

KW - Prostatic neoplasms

KW - Risk factors

KW - Transforming growth factor beta

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Association of polymorphisms in TGFB1 and prostate cancer prognosis

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