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 (Universidad de Las Palmas de Gran Canaria)
Valenciano, Almudena (Instituto Canario de Investigación del Cáncer)
Foro-Arnalot, Palmira (Hospital de la Esperanza)
Álvarez-Cubero, María Jesús (Universidad de Granada)
Cozar, José Manuel (Hospital Universitario Virgen de las Nieves (Granada))
Suárez-Novo, José Francisco (Hospital Universitari de Bellvitge)
Castells-Esteve, Manel (Hospital Universitari de Bellvitge)
Ayala-Gil, Adriana (Onkologikoa (Guipúscoa, País Basc))
Fernández-Gonzalo, Pablo (Onkologikoa (Guipúscoa, País Basc))
Ferrer, Montse (Institut Hospital del Mar d'Investigacions Mèdiques)
Guedea, Ferran (Institut Català d'Oncologia)
Sancho-Pardo, Gemma (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Craven-Bartle, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Ortiz-Gordillo, María José (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Cabrera-Roldán, Patricia (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Herrera-Ramos, Estefanía (Hospital Universitario de Gran Canaria Dr. Negrín)
Lara, Pedro C. (Universidad de Las Palmas de Gran Canaria)
Universitat Autònoma de Barcelona

Data:	2013
Resum:	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. © 2013 Henríquez-Hernández et al.
Ajuts:	Ministerio de Economía y Competitividad PI12/01867
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 8 Núm. 7 (23 2013) , p. e69735, ISSN 1932-6203

DOI: 10.1371/journal.pone.0069735
PMID: 23936089

9 p, 625.9 KB

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