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

被引：9

作者：

Alberto Henriquez-Hernandez, Luis ^{[1
,2
,3
]}

Valenciano, Almudena ^{[2
]}

Foro-Arnalot, Palmira ^{[4
]}

Jesus Alvarez-Cubero, Maria ^{[5
,6
]}

Manuel Cozar, Jose ^{[7
]}

Francisco Suarez-Novo, Jose ^{[8
]}

Castells-Esteve, Manel ^{[8
]}

Ayala-Gil, Adriana ^{[9
]}

Fernandez-Gonzalo, Pablo ^{[10
]}

Ferrer, Montse

Guedea, Ferran ^{[11
]}

Sancho-Pardo, Gemma ^{[12
]}

Craven-Bartle, Jordi ^{[12
]}

Jose Ortiz-Gordillo, Maria ^{[13
]}

Cabrera-Roldan, Patricia ^{[13
]}

Herrera-Ramos, Estefania ^{[14
]}

Lara, Pedro C. ^{[1
,2
,3
]}

机构：

[1] Hosp Univ Gran Canaria Dr Negrin, Dept Radiat Oncol, Las Palmas Gran Canaria, Spain

[2] Inst Canario Invest Canc, Las Palmas Gran Canaria, Spain

[3] Univ Las Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain

[4] Hosp Esperanza, Inst Oncol Radioterap, Barcelona, Spain

[5] Univ Granada, Fac Med, Legal Med & Toxicol Dept, Lab Genet Identificat, Granada, Spain

[6] Pfizer Univ Granada Andalusian Govt Ctr Genom & O, GENYO, Granada, Spain

[7] Hosp Univ Virgen de las Nieves, Dept Urol, Granada, Spain

[8] Hosp Univ Bellvite, Dept Urol, Barcelona, Spain

[9] Onkologikoa, Dept Radiat Oncol, Guipuzcoa, Spain

[10] Hosp Mar IMIM, Inst Recerca, Hlth Serv Res Grp, Barcelona, Spain

[11] ICO, Dept Radiat Oncol, Barcelona, Spain

[12] Hosp Santa Creu & Sant Pau, Dept Radiat Oncol, Barcelona, Spain

[13] Hosp Univ Virgen del Rocio, Dept Radiat Oncol, Seville, Spain

[14] Hosp Univ Gran Canaria Dr Negrin, Immonol Dept, Las Palmas Gran Canaria, Spain

来源：

PLOS ONE | 2013年 / 8卷 / 07期

关键词：

NORMAL TISSUE TOXICITY; BREAST-CANCER; RADIOTHERAPY TOXICITY; RADIATION TOXICITY; STRATIFICATION; PREDICTION; METABOLISM; PATTERNS; GENOMICS; XRCC3;

D O I：

10.1371/journal.pone.0069735

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (R) 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.

引用

页数：9

共 37 条

[1] Prediction of normal tissue toxicity as part of the individualized treatment with radiotherapy in oncology patients [J].