Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality

Daniel W. Lin, Liesel M. FitzGerald, Rong Fu, Erika M. Kwon, Siqun Lilly Zheng, Suzanne Kolb, Fredrik Wiklund, Pär Stattin, William B Isaacs, Jianfeng Xu, Elaine A. Ostrander, Ziding Feng, Henrik Grönberg, Janet L. Stanford

Research output: Contribution to journalArticle

Abstract

Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 topranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P trend = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated.

Original languageEnglish (US)
Pages (from-to)1928-1936
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number9
DOIs
StatePublished - Sep 2011

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Interleukin-4
Prostatic Neoplasms
Mortality
Genes
Single Nucleotide Polymorphism
Genotype
Population
Validation Studies
Genetic Markers
Survival

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality. / Lin, Daniel W.; FitzGerald, Liesel M.; Fu, Rong; Kwon, Erika M.; Zheng, Siqun Lilly; Kolb, Suzanne; Wiklund, Fredrik; Stattin, Pär; Isaacs, William B; Xu, Jianfeng; Ostrander, Elaine A.; Feng, Ziding; Grönberg, Henrik; Stanford, Janet L.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 9, 09.2011, p. 1928-1936.

Research output: Contribution to journalArticle

Lin, DW, FitzGerald, LM, Fu, R, Kwon, EM, Zheng, SL, Kolb, S, Wiklund, F, Stattin, P, Isaacs, WB, Xu, J, Ostrander, EA, Feng, Z, Grönberg, H & Stanford, JL 2011, 'Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 9, pp. 1928-1936. https://doi.org/10.1158/1055-9965.EPI-11-0236
Lin, Daniel W. ; FitzGerald, Liesel M. ; Fu, Rong ; Kwon, Erika M. ; Zheng, Siqun Lilly ; Kolb, Suzanne ; Wiklund, Fredrik ; Stattin, Pär ; Isaacs, William B ; Xu, Jianfeng ; Ostrander, Elaine A. ; Feng, Ziding ; Grönberg, Henrik ; Stanford, Janet L. / Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 9. pp. 1928-1936.
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title = "Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality",
abstract = "Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 topranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50{\%} (95{\%} CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P trend = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated.",
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T1 - Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality

AU - Lin, Daniel W.

AU - FitzGerald, Liesel M.

AU - Fu, Rong

AU - Kwon, Erika M.

AU - Zheng, Siqun Lilly

AU - Kolb, Suzanne

AU - Wiklund, Fredrik

AU - Stattin, Pär

AU - Isaacs, William B

AU - Xu, Jianfeng

AU - Ostrander, Elaine A.

AU - Feng, Ziding

AU - Grönberg, Henrik

AU - Stanford, Janet L.

PY - 2011/9

Y1 - 2011/9

N2 - Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 topranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P trend = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated.

AB - Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 topranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P trend = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated.

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SP - 1928

EP - 1936

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

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