Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence

Jiyoung Ahn, Adam S. Kibel, Jong Y. Park, Timothy R. Rebbeck, Hanna Rennert, Janet L. Stanford, Elaine A. Ostrander, Stephen Chanock, Ming Hsi Wang, Rama D. Mittal, William B Isaacs, Elizabeth A Platz, Richard B. Hayes

Research output: Contribution to journalArticle

Abstract

Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. Results: MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants.

Original languageEnglish (US)
Pages (from-to)1075-1081
Number of pages7
JournalClinical Cancer Research
Volume17
Issue number5
DOIs
StatePublished - Mar 1 2011

Fingerprint

Prostatic Neoplasms
Recurrence
Single Nucleotide Polymorphism
Genome-Wide Association Study
Logistic Models
Phenotype
Genetic Predisposition to Disease
Genetic Markers
Meta-Analysis
Case-Control Studies
Research Design
Alleles
Genotype
Genome
Weights and Measures

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ahn, J., Kibel, A. S., Park, J. Y., Rebbeck, T. R., Rennert, H., Stanford, J. L., ... Hayes, R. B. (2011). Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence. Clinical Cancer Research, 17(5), 1075-1081. https://doi.org/10.1158/1078-0432.CCR-10-0881

Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence. / Ahn, Jiyoung; Kibel, Adam S.; Park, Jong Y.; Rebbeck, Timothy R.; Rennert, Hanna; Stanford, Janet L.; Ostrander, Elaine A.; Chanock, Stephen; Wang, Ming Hsi; Mittal, Rama D.; Isaacs, William B; Platz, Elizabeth A; Hayes, Richard B.

In: Clinical Cancer Research, Vol. 17, No. 5, 01.03.2011, p. 1075-1081.

Research output: Contribution to journalArticle

Ahn, J, Kibel, AS, Park, JY, Rebbeck, TR, Rennert, H, Stanford, JL, Ostrander, EA, Chanock, S, Wang, MH, Mittal, RD, Isaacs, WB, Platz, EA & Hayes, RB 2011, 'Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence', Clinical Cancer Research, vol. 17, no. 5, pp. 1075-1081. https://doi.org/10.1158/1078-0432.CCR-10-0881
Ahn, Jiyoung ; Kibel, Adam S. ; Park, Jong Y. ; Rebbeck, Timothy R. ; Rennert, Hanna ; Stanford, Janet L. ; Ostrander, Elaine A. ; Chanock, Stephen ; Wang, Ming Hsi ; Mittal, Rama D. ; Isaacs, William B ; Platz, Elizabeth A ; Hayes, Richard B. / Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 5. pp. 1075-1081.
@article{0e067b9f8b98484c9d644c2ddc64949b,
title = "Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence",
abstract = "Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. Results: MSMB rs10993994 (per variant allele summary RR = 1.24, 95{\%} CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95{\%} CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95{\%} CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants.",
author = "Jiyoung Ahn and Kibel, {Adam S.} and Park, {Jong Y.} and Rebbeck, {Timothy R.} and Hanna Rennert and Stanford, {Janet L.} and Ostrander, {Elaine A.} and Stephen Chanock and Wang, {Ming Hsi} and Mittal, {Rama D.} and Isaacs, {William B} and Platz, {Elizabeth A} and Hayes, {Richard B.}",
year = "2011",
month = "3",
day = "1",
doi = "10.1158/1078-0432.CCR-10-0881",
language = "English (US)",
volume = "17",
pages = "1075--1081",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence

AU - Ahn, Jiyoung

AU - Kibel, Adam S.

AU - Park, Jong Y.

AU - Rebbeck, Timothy R.

AU - Rennert, Hanna

AU - Stanford, Janet L.

AU - Ostrander, Elaine A.

AU - Chanock, Stephen

AU - Wang, Ming Hsi

AU - Mittal, Rama D.

AU - Isaacs, William B

AU - Platz, Elizabeth A

AU - Hayes, Richard B.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. Results: MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants.

AB - Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. Results: MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants.

UR - http://www.scopus.com/inward/record.url?scp=79952269693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952269693&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-10-0881

DO - 10.1158/1078-0432.CCR-10-0881

M3 - Article

VL - 17

SP - 1075

EP - 1081

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 5

ER -