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Replication of a Genetic Variant for Prostate Cancer-Specific Mortality
BACKGROUND: Few genetic variants have been confirmed as being associated with prostate cancer-specific mortality (PCSM). A recent study identified 22 candidate single-nucleotide polymorphisms (SNPs) associated with PCSM in a Seattle-based patient cohort. Five of these associations were replicated in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537383/ https://www.ncbi.nlm.nih.gov/pubmed/25939514 http://dx.doi.org/10.1038/pcan.2015.18 |
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author | Penney, Kathryn L. Shui, Irene M. Feng, Ziding Sesso, Howard D. Stampfer, Meir J. Stanford, Janet L. |
author_facet | Penney, Kathryn L. Shui, Irene M. Feng, Ziding Sesso, Howard D. Stampfer, Meir J. Stanford, Janet L. |
author_sort | Penney, Kathryn L. |
collection | PubMed |
description | BACKGROUND: Few genetic variants have been confirmed as being associated with prostate cancer-specific mortality (PCSM). A recent study identified 22 candidate single-nucleotide polymorphisms (SNPs) associated with PCSM in a Seattle-based patient cohort. Five of these associations were replicated in an independent Swedish cohort. METHODS: We genotyped these 22 SNPs in Physicians’ Health Study (PHS) participants diagnosed with prostate cancer (PCa). Utilizing the same model found to be most significant in the Seattle cohort, we examined the association of these SNPs with lethal disease with Cox proportional hazards models. RESULTS: One SNP, rs5993891 in the ARVCF gene on chromosome 22q11, which had also replicated in the Swedish cohort, was also significantly associated with PCSM in the PHS cohort (hazard ratio (HR)=0.32; P=0.01). When we tested this SNP in an additional cohort (Health Professionals Follow-up Study, HPFS), the association was null (HR=0.95, P=0.90); however, a meta-analysis across all studies showed a statistically significant association with a HR of 0.52 (0.29–0.93, P=0.03). CONCLUSIONS: The association of rs5993891 with PCSM was further replicated in PHS and remains significant in a meta-analysis, though there was no association in HPFS. This SNP may contribute to a genetic panel of SNPs to determine at diagnosis whether a patient is more likely to exhibit an indolent or aggressive form of PCa. This study also emphasizes the importance of multiple rounds of replication. |
format | Online Article Text |
id | pubmed-4537383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45373832016-03-01 Replication of a Genetic Variant for Prostate Cancer-Specific Mortality Penney, Kathryn L. Shui, Irene M. Feng, Ziding Sesso, Howard D. Stampfer, Meir J. Stanford, Janet L. Prostate Cancer Prostatic Dis Article BACKGROUND: Few genetic variants have been confirmed as being associated with prostate cancer-specific mortality (PCSM). A recent study identified 22 candidate single-nucleotide polymorphisms (SNPs) associated with PCSM in a Seattle-based patient cohort. Five of these associations were replicated in an independent Swedish cohort. METHODS: We genotyped these 22 SNPs in Physicians’ Health Study (PHS) participants diagnosed with prostate cancer (PCa). Utilizing the same model found to be most significant in the Seattle cohort, we examined the association of these SNPs with lethal disease with Cox proportional hazards models. RESULTS: One SNP, rs5993891 in the ARVCF gene on chromosome 22q11, which had also replicated in the Swedish cohort, was also significantly associated with PCSM in the PHS cohort (hazard ratio (HR)=0.32; P=0.01). When we tested this SNP in an additional cohort (Health Professionals Follow-up Study, HPFS), the association was null (HR=0.95, P=0.90); however, a meta-analysis across all studies showed a statistically significant association with a HR of 0.52 (0.29–0.93, P=0.03). CONCLUSIONS: The association of rs5993891 with PCSM was further replicated in PHS and remains significant in a meta-analysis, though there was no association in HPFS. This SNP may contribute to a genetic panel of SNPs to determine at diagnosis whether a patient is more likely to exhibit an indolent or aggressive form of PCa. This study also emphasizes the importance of multiple rounds of replication. 2015-05-05 2015-09 /pmc/articles/PMC4537383/ /pubmed/25939514 http://dx.doi.org/10.1038/pcan.2015.18 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Penney, Kathryn L. Shui, Irene M. Feng, Ziding Sesso, Howard D. Stampfer, Meir J. Stanford, Janet L. Replication of a Genetic Variant for Prostate Cancer-Specific Mortality |
title | Replication of a Genetic Variant for Prostate Cancer-Specific Mortality |
title_full | Replication of a Genetic Variant for Prostate Cancer-Specific Mortality |
title_fullStr | Replication of a Genetic Variant for Prostate Cancer-Specific Mortality |
title_full_unstemmed | Replication of a Genetic Variant for Prostate Cancer-Specific Mortality |
title_short | Replication of a Genetic Variant for Prostate Cancer-Specific Mortality |
title_sort | replication of a genetic variant for prostate cancer-specific mortality |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537383/ https://www.ncbi.nlm.nih.gov/pubmed/25939514 http://dx.doi.org/10.1038/pcan.2015.18 |
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