Lin, DW and Fitzgerald, LM and Fu, R and Kwon, EM and Zheng, SL and Kibb, S and Wiklund, F and Stattin, P and Isaacs, WB and Xu, J and Ostrander, EA and Feng, Z and Gronberg, H and Stanford, JL, Genetic Variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF Genes Are Prognostic Markers of Prostate Cancer-Specific Mortality, Cancer Epidemiology, Biomarkers and Prevention, 20, (9) pp. 1928-36. ISSN 1055-9965 (2011) [Refereed Article]
Copyright 2011 American Association for Cancer Research.
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 top-ranking 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.
|Item Type:||Refereed Article|
|Keywords:||Prostate Cancer Mortality|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Oncology and carcinogenesis|
|Research Field:||Cancer genetics|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Fitzgerald, LM (Dr Liesel Fitzgerald)|
|Web of Science® Times Cited:||57|
|Deposited By:||Menzies Institute for Medical Research|
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