Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.

Few biomarkers are available to predict prostate cancer risk. Single nucleotide polymorphisms (SNPs) tend to have weak individual effects but, in combination, they have stronger predictive value. Adipokine pathways have been implicated in the pathogenesis. We used a candidate pathway approach to inv...

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Autores principales:	Ricardo J T Ribeiro, Cátia P D Monteiro, Andreia S M Azevedo, Virgínia F M Cunha, Agnihotram V Ramanakumar, Avelino M Fraga, Francisco M Pina, Carlos M S Lopes, Rui M Medeiros, Eduardo L Franco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6328e273a3604ed0b6499cdddb261525
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spelling	oai:doaj.org-article:6328e273a3604ed0b6499cdddb2615252021-11-18T07:13:36ZPerformance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.1932-620310.1371/journal.pone.0039236https://doaj.org/article/6328e273a3604ed0b6499cdddb2615252012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792137/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Few biomarkers are available to predict prostate cancer risk. Single nucleotide polymorphisms (SNPs) tend to have weak individual effects but, in combination, they have stronger predictive value. Adipokine pathways have been implicated in the pathogenesis. We used a candidate pathway approach to investigate 29 functional SNPs in key genes from relevant adipokine pathways in a sample of 1006 men eligible for prostate biopsy. We used stepwise multivariate logistic regression and bootstrapping to develop a multilocus genetic risk score by weighting each risk SNP empirically based on its association with disease. Seven common functional polymorphisms were associated with overall and high-grade prostate cancer (Gleason≥7), whereas three variants were associated with high metastatic-risk prostate cancer (PSA≥20 ng/mL and/or Gleason≥8). The addition of genetic variants to age and PSA improved the predictive accuracy for overall and high-grade prostate cancer, using either the area under the receiver-operating characteristics curves (P<0.02), the net reclassification improvement (P<0.001) and integrated discrimination improvement (P<0.001) measures. These results suggest that functional polymorphisms in adipokine pathways may act individually and cumulatively to affect risk and severity of prostate cancer, supporting the influence of adipokine pathways in the pathogenesis of prostate cancer. Use of such adipokine multilocus genetic risk score can enhance the predictive value of PSA and age in estimating absolute risk, which supports further evaluation of its clinical significance.Ricardo J T RibeiroCátia P D MonteiroAndreia S M AzevedoVirgínia F M CunhaAgnihotram V RamanakumarAvelino M FragaFrancisco M PinaCarlos M S LopesRui M MedeirosEduardo L FrancoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39236 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ricardo J T Ribeiro Cátia P D Monteiro Andreia S M Azevedo Virgínia F M Cunha Agnihotram V Ramanakumar Avelino M Fraga Francisco M Pina Carlos M S Lopes Rui M Medeiros Eduardo L Franco Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
description	Few biomarkers are available to predict prostate cancer risk. Single nucleotide polymorphisms (SNPs) tend to have weak individual effects but, in combination, they have stronger predictive value. Adipokine pathways have been implicated in the pathogenesis. We used a candidate pathway approach to investigate 29 functional SNPs in key genes from relevant adipokine pathways in a sample of 1006 men eligible for prostate biopsy. We used stepwise multivariate logistic regression and bootstrapping to develop a multilocus genetic risk score by weighting each risk SNP empirically based on its association with disease. Seven common functional polymorphisms were associated with overall and high-grade prostate cancer (Gleason≥7), whereas three variants were associated with high metastatic-risk prostate cancer (PSA≥20 ng/mL and/or Gleason≥8). The addition of genetic variants to age and PSA improved the predictive accuracy for overall and high-grade prostate cancer, using either the area under the receiver-operating characteristics curves (P<0.02), the net reclassification improvement (P<0.001) and integrated discrimination improvement (P<0.001) measures. These results suggest that functional polymorphisms in adipokine pathways may act individually and cumulatively to affect risk and severity of prostate cancer, supporting the influence of adipokine pathways in the pathogenesis of prostate cancer. Use of such adipokine multilocus genetic risk score can enhance the predictive value of PSA and age in estimating absolute risk, which supports further evaluation of its clinical significance.
format	article
author	Ricardo J T Ribeiro Cátia P D Monteiro Andreia S M Azevedo Virgínia F M Cunha Agnihotram V Ramanakumar Avelino M Fraga Francisco M Pina Carlos M S Lopes Rui M Medeiros Eduardo L Franco
author_facet	Ricardo J T Ribeiro Cátia P D Monteiro Andreia S M Azevedo Virgínia F M Cunha Agnihotram V Ramanakumar Avelino M Fraga Francisco M Pina Carlos M S Lopes Rui M Medeiros Eduardo L Franco
author_sort	Ricardo J T Ribeiro
title	Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
title_short	Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
title_full	Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
title_fullStr	Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
title_full_unstemmed	Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
title_sort	performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6328e273a3604ed0b6499cdddb261525
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Performance of an adipokine pathway-based multilocus genetic risk score for prostate cancer risk prediction.

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