RT Journal Article
T1 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.
A1 Henríquez-Hernández, Luis Alberto
A1 Valenciano, Almudena
A1 Foro-Arnalot, Palmira
A1 Alvarez-Cubero, María Jesús
A1 Cozar, José Manuel
A1 Suárez-Novo, José Francisco
A1 Castells-Esteve, Manel
A1 Ayala-Gil, Adriana
A1 Fernández-Gonzalo, Pablo
A1 Ferrer, Montse
A1 Guedea, Ferrán
A1 Sancho-Pardo, Gemma
A1 Craven-Bartle, Jordi
A1 Ortiz-Gordillo, María José
A1 Cabrera-Roldán, Patricia
A1 Herrera-Ramos, Estefanía
A1 Lara, Pedro C
K1 Neoplasias de la Próstata
K1 Genotipo
K1 España
K1 Radioterapia Ayuvante
K1 Humanos
K1 Polimorfismo Genético
K1 Reparación del ADN
K1 Estudios de Cohortes
K1 Polimorfismo de Nucleótido Simple
K1 Masculino
AB BACKGROUNDDifferences 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.OBJECTIVETo 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 PARTICIPANTSA 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 ANALYSISComparisons 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 LIMITATIONSWe 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.CONCLUSIONDifferences 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.
PB Public Library of Science
YR 2013
FD 2013-07-23
LK http://hdl.handle.net/10668/1372
UL http://hdl.handle.net/10668/1372
LA en
NO Henríquez-Hernández LA, Valenciano A, Foro-Arnalot P, Alvarez-Cubero MJ, Cozar JM, Suárez-Novo JF, 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. 2013; 8(7):e69735
NO Journal Article;
DS RISalud
RD Apr 5, 2025