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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

BACKGROUND: 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. OBJECTIVE: To evaluate the genotypic distribution of SNPs in a wide set of Spanish pro...

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Autores principales: Henríquez-Hernández, Luis Alberto, Valenciano, Almudena, Foro-Arnalot, Palmira, Álvarez-Cubero, María Jesús, Cozar, José Manuel, Suárez-Novo, José Francisco, Castells-Esteve, Manel, Ayala-Gil, Adriana, Fernández-Gonzalo, Pablo, Ferrer, Montse, Guedea, Ferrán, Sancho-Pardo, Gemma, Craven-Bartle, Jordi, Ortiz-Gordillo, María José, Cabrera-Roldán, Patricia, Herrera-Ramos, Estefanía, Lara, Pedro C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720621/
https://www.ncbi.nlm.nih.gov/pubmed/23936089
http://dx.doi.org/10.1371/journal.pone.0069735
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author Henríquez-Hernández, Luis Alberto
Valenciano, Almudena
Foro-Arnalot, Palmira
Álvarez-Cubero, María Jesús
Cozar, José Manuel
Suárez-Novo, José Francisco
Castells-Esteve, Manel
Ayala-Gil, Adriana
Fernández-Gonzalo, Pablo
Ferrer, Montse
Guedea, Ferrán
Sancho-Pardo, Gemma
Craven-Bartle, Jordi
Ortiz-Gordillo, María José
Cabrera-Roldán, Patricia
Herrera-Ramos, Estefanía
Lara, Pedro C.
author_facet Henríquez-Hernández, Luis Alberto
Valenciano, Almudena
Foro-Arnalot, Palmira
Álvarez-Cubero, María Jesús
Cozar, José Manuel
Suárez-Novo, José Francisco
Castells-Esteve, Manel
Ayala-Gil, Adriana
Fernández-Gonzalo, Pablo
Ferrer, Montse
Guedea, Ferrán
Sancho-Pardo, Gemma
Craven-Bartle, Jordi
Ortiz-Gordillo, María José
Cabrera-Roldán, Patricia
Herrera-Ramos, Estefanía
Lara, Pedro C.
author_sort Henríquez-Hernández, Luis Alberto
collection PubMed
description BACKGROUND: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSION: 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.
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spelling pubmed-37206212013-08-09 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 Henríquez-Hernández, Luis Alberto Valenciano, Almudena Foro-Arnalot, Palmira Álvarez-Cubero, María Jesús Cozar, José Manuel Suárez-Novo, José Francisco Castells-Esteve, Manel Ayala-Gil, Adriana Fernández-Gonzalo, Pablo Ferrer, Montse Guedea, Ferrán Sancho-Pardo, Gemma Craven-Bartle, Jordi Ortiz-Gordillo, María José Cabrera-Roldán, Patricia Herrera-Ramos, Estefanía Lara, Pedro C. PLoS One Research Article BACKGROUND: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSION: 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. Public Library of Science 2013-07-23 /pmc/articles/PMC3720621/ /pubmed/23936089 http://dx.doi.org/10.1371/journal.pone.0069735 Text en © 2013 Henríquez-Hernández et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Henríquez-Hernández, Luis Alberto
Valenciano, Almudena
Foro-Arnalot, Palmira
Álvarez-Cubero, María Jesús
Cozar, José Manuel
Suárez-Novo, José Francisco
Castells-Esteve, Manel
Ayala-Gil, Adriana
Fernández-Gonzalo, Pablo
Ferrer, Montse
Guedea, Ferrán
Sancho-Pardo, Gemma
Craven-Bartle, Jordi
Ortiz-Gordillo, María José
Cabrera-Roldán, Patricia
Herrera-Ramos, Estefanía
Lara, Pedro C.
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 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_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_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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720621/
https://www.ncbi.nlm.nih.gov/pubmed/23936089
http://dx.doi.org/10.1371/journal.pone.0069735
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