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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URI: http://hdl.handle.net/10481/31152
ISSN: 1932-6203
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Autor
Henríquez-Hernández, Luis Alberto; Valenciano, Almudena; Foro-Arnalot, Palmira; Álvarez Cubero, María Jesús; Cózar Olmo, 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.
Editorial
Public Library of Science (PLOS)
Materia
Canaries
 
DNA repair
 
Ethnic epidemiology
 
Genotyping
 
Haplotypes
 
Prostate cancer
 
Toxicity
 
Variant genotypes
 
Fecha
2013
Referencia bibliográfica
Henríquez-Hernández, L.A.; et al. 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. Plos One, 8(7): e69735 (2013). [http://hdl.handle.net/10481/31152]
Patrocinador
This work was subsidized by a grant from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad from Spain), ID: PI12/01867. Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC).
Resumen
[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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