Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.

<h4>Background</h4>Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics.<h4>Objective</h4>To evaluate the genotypic distribution...

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Autores principales:	Luis Alberto Henríquez-Hernández, Almudena Valenciano, Palmira Foro-Arnalot, María Jesús Alvarez-Cubero, José Manuel Cozar, José Francisco Suárez-Novo, Manel Castells-Esteve, Adriana Ayala-Gil, Pablo Fernández-Gonzalo, Montse Ferrer, Ferrán Guedea, Gemma Sancho-Pardo, Jordi Craven-Bartle, María José Ortiz-Gordillo, Patricia Cabrera-Roldán, Estefanía Herrera-Ramos, Pedro C Lara
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c42e267343b64c47a5784cc438038160
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spelling	oai:doaj.org-article:c42e267343b64c47a5784cc4380381602021-11-18T09:03:14ZPolymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.1932-620310.1371/journal.pone.0069735https://doaj.org/article/c42e267343b64c47a5784cc4380381602013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936089/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics.<h4>Objective</h4>To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias.<h4>Design setting and participants</h4>A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler.<h4>Outcome measurements and statistical analysis</h4>Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer.<h4>Results and limitations</h4>We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics.<h4>Conclusion</h4>Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.Luis Alberto Henríquez-HernándezAlmudena ValencianoPalmira Foro-ArnalotMaría Jesús Alvarez-CuberoJosé Manuel CozarJosé Francisco Suárez-NovoManel Castells-EsteveAdriana Ayala-GilPablo Fernández-GonzaloMontse FerrerFerrán GuedeaGemma Sancho-PardoJordi Craven-BartleMaría José Ortiz-GordilloPatricia Cabrera-RoldánEstefanía Herrera-RamosPedro C LaraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69735 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luis Alberto Henríquez-Hernández Almudena Valenciano Palmira Foro-Arnalot María Jesús Alvarez-Cubero José Manuel Cozar José Francisco Suárez-Novo Manel Castells-Esteve Adriana Ayala-Gil Pablo Fernández-Gonzalo Montse Ferrer Ferrán Guedea Gemma Sancho-Pardo Jordi Craven-Bartle María José Ortiz-Gordillo Patricia Cabrera-Roldán Estefanía Herrera-Ramos Pedro C Lara Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.
description	<h4>Background</h4>Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics.<h4>Objective</h4>To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias.<h4>Design setting and participants</h4>A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler.<h4>Outcome measurements and statistical analysis</h4>Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer.<h4>Results and limitations</h4>We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics.<h4>Conclusion</h4>Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.
format	article
author	Luis Alberto Henríquez-Hernández Almudena Valenciano Palmira Foro-Arnalot María Jesús Alvarez-Cubero José Manuel Cozar José Francisco Suárez-Novo Manel Castells-Esteve Adriana Ayala-Gil Pablo Fernández-Gonzalo Montse Ferrer Ferrán Guedea Gemma Sancho-Pardo Jordi Craven-Bartle María José Ortiz-Gordillo Patricia Cabrera-Roldán Estefanía Herrera-Ramos Pedro C Lara
author_facet	Luis Alberto Henríquez-Hernández Almudena Valenciano Palmira Foro-Arnalot María Jesús Alvarez-Cubero José Manuel Cozar José Francisco Suárez-Novo Manel Castells-Esteve Adriana Ayala-Gil Pablo Fernández-Gonzalo Montse Ferrer Ferrán Guedea Gemma Sancho-Pardo Jordi Craven-Bartle María José Ortiz-Gordillo Patricia Cabrera-Roldán Estefanía Herrera-Ramos Pedro C Lara
author_sort	Luis Alberto Henríquez-Hernández
title	Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.
title_short	Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.
title_full	Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.
title_fullStr	Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.
title_full_unstemmed	Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.
title_sort	polymorphisms in dna-repair genes in a cohort of prostate cancer patients from different areas in spain: heterogeneity between populations as a confounding factor in association studies.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c42e267343b64c47a5784cc438038160
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Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.

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