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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2013 |
| Country: | España |
| Institution: | Universitat Pompeu Fabra |
| Repository: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/53712 |
| Online Access: | http://hdl.handle.net/10230/53712 http://dx.doi.org/10.1371/journal.pone.0069735 |
| Access Level: | Open access |
| Keyword: | Single nucleotide polymorphisms Canaries Variant genotypes Toxicity DNA repair Haplotypes Prostate cancer Genotyping |
| _version_ | 1878740576278413312 |
|---|---|
| author | Henríquez Hernández, Luis Alberto |
| author2 | 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 Forés, Maria Montserrat Guedea, Ferrán Sancho-Pardo, Gemma Craven-Bartle, Jordi Ortiz Gordillo, María José Cabrera Roldán, Patricia Herrera Ramos, Estefanía Lara, Pedro C. |
| author2_role | author author author author author author author author author author author author author author author author |
| author_browse | Ayala-Gil, Adriana Cabrera Roldán, Patricia Castells Esteve, Manel Cozar, José Manuel Craven-Bartle, Jordi Fernández Gonzalo, Pablo Ferrer Forés, Maria Montserrat Foro Arnalot, Palmira Guedea, Ferrán Henríquez Hernández, Luis Alberto Herrera Ramos, Estefanía Lara, Pedro C. Ortiz Gordillo, María José Sancho-Pardo, Gemma Suárez Novo, José Francisco Valenciano, Almudena Álvarez Cubero, María Jesús |
| 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 Forés, Maria Montserrat Guedea, Ferrán Sancho-Pardo, Gemma Craven-Bartle, Jordi Ortiz Gordillo, María José Cabrera Roldán, Patricia Herrera Ramos, Estefanía Lara, Pedro C. |
| author_role | author |
| collection | Repositorio Digital de la UPF |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_d58cffa0b553bcd2fda105b2f69a7a5a |
| institution | Universitat Pompeu Fabra |
| instname_str | Universitat Pompeu Fabra |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repositori.upf.edu:10230/53712 |
| publishDate | 2013 |
| publishDateSort | 2013 |
| publisher | Public Library of Science (PLoS) |
| publisherStr | Public Library of Science (PLoS) |
| reponame_str | Repositorio Digital de la UPF |
| spelling | 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 Forés, Maria Montserrat Guedea, Ferrán Sancho-Pardo, Gemma Craven-Bartle, Jordi Ortiz Gordillo, María José Cabrera Roldán, Patricia Herrera Ramos, Estefanía Lara, Pedro C. Single nucleotide polymorphisms Canaries Variant genotypes Toxicity DNA repair Haplotypes Prostate cancer Genotyping 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 (PLoS) http://hdl.handle.net/10230/53712 http://dx.doi.org/10.1371/journal.pone.0069735 |
| spellingShingle | 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 Single nucleotide polymorphisms Canaries Variant genotypes Toxicity DNA repair Haplotypes Prostate cancer Genotyping |
| status_str | publishedVersion |
| 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 | Single nucleotide polymorphisms Canaries Variant genotypes Toxicity DNA repair Haplotypes Prostate cancer Genotyping |
| topic_facet | Single nucleotide polymorphisms Canaries Variant genotypes Toxicity DNA repair Haplotypes Prostate cancer Genotyping |
| url | http://hdl.handle.net/10230/53712 http://dx.doi.org/10.1371/journal.pone.0069735 |