Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain.
PLoS One. 2013 Jul 23;8(7):e69735. doi: 10.1371/journal.pone.0069735. Print 2013.
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.
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.
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.
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.
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.
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.
在放射基因组学中进行的典型关联研究中，个体之间基因型分布的差异是一个经常被低估的重要混杂因素。
评估广泛的西班牙前列腺癌患者中 10 个 SNP 的基因型分布，以确定人群的同质性并揭示潜在的偏差。
设计、地点和参与者：对来自安达卢西亚、巴斯克地区、加那利群岛和加泰罗尼亚的 601 名前列腺癌患者进行了 10 个位于 6 个不同与 DNA 修复相关基因（XRCC1(rs25487、rs25489、rs1799782)、ERCC2(rs13181)、ERCC1(rs11615)、LIG4(rs1805388、rs1805386)、ATM(rs17503908、rs1800057)和 P53(rs1042522)的 SNP 进行基因分型。SNP 基因分型在 Biotrove OpenArray®NT Cycler 上进行。
使用基于网络的 SNPator 环境确定了人群之间基因型和等位基因频率的比较，以及单倍型分析。使用 R 包中实现的 SnpMatrix 和 XSnpMatrix 类和方法进行主成分分析。使用 MultiExperiment Viewer 对 SNP 进行无监督层次聚类。
我们观察到 10 个 SNP 中的 4 个 SNP 的基因型分布在研究人群中存在统计学差异，安达卢西亚和加泰罗尼亚之间的差异最大。聚类分析、主成分分析和人群中单倍型的差异分布证实了这些观察结果。由于未考虑肿瘤特征，因此某些多态性可能会以影响肿瘤特征的相同方式影响辐射诱导毒性的相关 SNP，或者它可能成为其他疾病特征的风险因素。
同一族群不同族群之间基因型分布的差异可能是导致与辐射诱导毒性相关的 SNP 缺乏验证的一个重要混杂因素，尤其是当对来自不同国家的受试者进行广泛的荟萃分析时。
