No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes

Jerry Jaboin, Misun Hwang, Carmen A. Perez, Calvin Cooper, Heidi Chen, Chuanzhong Ye, Qiuyin Cai, Marcia L. Wills, Bo Lu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: Mouse double-minute 2 (MDM2) SNP309 polymorphism (T>G) has been correlated with an increased risk of cancer in multiple tumor types. MDM2 overexpression has shown to be weakly associated with distant tumor metastases, and down-regulation of MDM2 via antisense oligonucleotides in vitro has resulted in the radiosensitization of prostate cancer cell lines. Based on these results, we decided to evaluate the role of MDM2 SNP309 in the context of histopathologic parameters and clinical outcomes in prostate cancer tumors. Materials and methods: The population consisted of 212 consecutive prostate cancer patients who underwent radical prostatectomy between 1997 and 1999 at Vanderbilt University Medical Center. Two hundred eight of the samples were successfully genotyped for the MDM2 SNP309 polymorphism. Correlations between the polymorphism, recurrence, and survival data were analyzed using univariate and multivariate genetic models. Results: The only prognostic factor predictive of overall survival in our study was Gleason score (P < 0.005). Using Χ2 analysis, we determined that the MDM2 SNP309 polymorphism had no significant association with race (P = 0.7512), patient's age at diagnosis (P = 0.6820), pre-prostatectomy PSA level (P = 0.8606), Gleason's score (P = 0.4839), surgical margin status (P = 1.0000), extracapsular extension (P = 0.6175), and disease stage (P = 0.4945). In addition, there was no significant difference in 3-year recurrence-free survival (P = 0.218), or 8-year overall survival (P = 0.376). Conclusions: Our study finds no evidence for association of the MDM2 SNP309 polymorphism with clinicopathologic variables, recurrence risk, and overall survival outcome in prostate cancer.

Original languageEnglish (US)
Pages (from-to)319-323
Number of pages5
JournalUrologic Oncology: Seminars and Original Investigations
Volume29
Issue number3
DOIs
StatePublished - May 2011
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Survival
Neoplasm Grading
Prostatectomy
Recurrence
Neoplasms
Antisense Oligonucleotides
Genetic Models
Down-Regulation
Neoplasm Metastasis
Cell Line
Population

Keywords

  • MDM2
  • Polymorphism
  • Prognosis
  • Promoter
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes. / Jaboin, Jerry; Hwang, Misun; Perez, Carmen A.; Cooper, Calvin; Chen, Heidi; Ye, Chuanzhong; Cai, Qiuyin; Wills, Marcia L.; Lu, Bo.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 29, No. 3, 05.2011, p. 319-323.

Research output: Contribution to journalArticle

Jaboin, Jerry ; Hwang, Misun ; Perez, Carmen A. ; Cooper, Calvin ; Chen, Heidi ; Ye, Chuanzhong ; Cai, Qiuyin ; Wills, Marcia L. ; Lu, Bo. / No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes. In: Urologic Oncology: Seminars and Original Investigations. 2011 ; Vol. 29, No. 3. pp. 319-323.
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abstract = "Objectives: Mouse double-minute 2 (MDM2) SNP309 polymorphism (T>G) has been correlated with an increased risk of cancer in multiple tumor types. MDM2 overexpression has shown to be weakly associated with distant tumor metastases, and down-regulation of MDM2 via antisense oligonucleotides in vitro has resulted in the radiosensitization of prostate cancer cell lines. Based on these results, we decided to evaluate the role of MDM2 SNP309 in the context of histopathologic parameters and clinical outcomes in prostate cancer tumors. Materials and methods: The population consisted of 212 consecutive prostate cancer patients who underwent radical prostatectomy between 1997 and 1999 at Vanderbilt University Medical Center. Two hundred eight of the samples were successfully genotyped for the MDM2 SNP309 polymorphism. Correlations between the polymorphism, recurrence, and survival data were analyzed using univariate and multivariate genetic models. Results: The only prognostic factor predictive of overall survival in our study was Gleason score (P < 0.005). Using Χ2 analysis, we determined that the MDM2 SNP309 polymorphism had no significant association with race (P = 0.7512), patient's age at diagnosis (P = 0.6820), pre-prostatectomy PSA level (P = 0.8606), Gleason's score (P = 0.4839), surgical margin status (P = 1.0000), extracapsular extension (P = 0.6175), and disease stage (P = 0.4945). In addition, there was no significant difference in 3-year recurrence-free survival (P = 0.218), or 8-year overall survival (P = 0.376). Conclusions: Our study finds no evidence for association of the MDM2 SNP309 polymorphism with clinicopathologic variables, recurrence risk, and overall survival outcome in prostate cancer.",
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T1 - No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes

AU - Jaboin, Jerry

AU - Hwang, Misun

AU - Perez, Carmen A.

AU - Cooper, Calvin

AU - Chen, Heidi

AU - Ye, Chuanzhong

AU - Cai, Qiuyin

AU - Wills, Marcia L.

AU - Lu, Bo

PY - 2011/5

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N2 - Objectives: Mouse double-minute 2 (MDM2) SNP309 polymorphism (T>G) has been correlated with an increased risk of cancer in multiple tumor types. MDM2 overexpression has shown to be weakly associated with distant tumor metastases, and down-regulation of MDM2 via antisense oligonucleotides in vitro has resulted in the radiosensitization of prostate cancer cell lines. Based on these results, we decided to evaluate the role of MDM2 SNP309 in the context of histopathologic parameters and clinical outcomes in prostate cancer tumors. Materials and methods: The population consisted of 212 consecutive prostate cancer patients who underwent radical prostatectomy between 1997 and 1999 at Vanderbilt University Medical Center. Two hundred eight of the samples were successfully genotyped for the MDM2 SNP309 polymorphism. Correlations between the polymorphism, recurrence, and survival data were analyzed using univariate and multivariate genetic models. Results: The only prognostic factor predictive of overall survival in our study was Gleason score (P < 0.005). Using Χ2 analysis, we determined that the MDM2 SNP309 polymorphism had no significant association with race (P = 0.7512), patient's age at diagnosis (P = 0.6820), pre-prostatectomy PSA level (P = 0.8606), Gleason's score (P = 0.4839), surgical margin status (P = 1.0000), extracapsular extension (P = 0.6175), and disease stage (P = 0.4945). In addition, there was no significant difference in 3-year recurrence-free survival (P = 0.218), or 8-year overall survival (P = 0.376). Conclusions: Our study finds no evidence for association of the MDM2 SNP309 polymorphism with clinicopathologic variables, recurrence risk, and overall survival outcome in prostate cancer.

AB - Objectives: Mouse double-minute 2 (MDM2) SNP309 polymorphism (T>G) has been correlated with an increased risk of cancer in multiple tumor types. MDM2 overexpression has shown to be weakly associated with distant tumor metastases, and down-regulation of MDM2 via antisense oligonucleotides in vitro has resulted in the radiosensitization of prostate cancer cell lines. Based on these results, we decided to evaluate the role of MDM2 SNP309 in the context of histopathologic parameters and clinical outcomes in prostate cancer tumors. Materials and methods: The population consisted of 212 consecutive prostate cancer patients who underwent radical prostatectomy between 1997 and 1999 at Vanderbilt University Medical Center. Two hundred eight of the samples were successfully genotyped for the MDM2 SNP309 polymorphism. Correlations between the polymorphism, recurrence, and survival data were analyzed using univariate and multivariate genetic models. Results: The only prognostic factor predictive of overall survival in our study was Gleason score (P < 0.005). Using Χ2 analysis, we determined that the MDM2 SNP309 polymorphism had no significant association with race (P = 0.7512), patient's age at diagnosis (P = 0.6820), pre-prostatectomy PSA level (P = 0.8606), Gleason's score (P = 0.4839), surgical margin status (P = 1.0000), extracapsular extension (P = 0.6175), and disease stage (P = 0.4945). In addition, there was no significant difference in 3-year recurrence-free survival (P = 0.218), or 8-year overall survival (P = 0.376). Conclusions: Our study finds no evidence for association of the MDM2 SNP309 polymorphism with clinicopathologic variables, recurrence risk, and overall survival outcome in prostate cancer.

KW - MDM2

KW - Polymorphism

KW - Prognosis

KW - Promoter

KW - Prostate cancer

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