Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients

BMC Cancer

Research Article

María Berdasco¹  Manel Esteller²  Miguel Martínez³  Nora Artagaveytia⁴  Mónica Sans⁵  Pedro C Hidalgo⁶  Mónica Cappetta⁷  Jimena Hochmann⁷  Bernardo Bertoni⁷  Rick Kittles⁸  Carolina Bonilla⁹ 

[1] Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de LLobregat, Barcelona, Catalonia, Spain;Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de LLobregat, Barcelona, Catalonia, Spain;Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain;Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain;Cátedra de Dermatología, Hospital de Clínicas “Manuel Quintela”, Universidad de la República, Montevideo, Uruguay;Departamento Básico de Medicina, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay;Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay;Centro Universitario de Tacuarembó, Universidad de la República, Tacuarembó, Uruguay;Departamento de Genética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Department of Surgery and Public Health, University of Arizona, Tucson, USA;School of Social and Community Medicine, University of Bristol, Bristol, UK;

关键词: Genetic ancestry;    DNA methylation;    Admixture;    Cancer;   

DOI  :  10.1186/s12885-015-1461-0

 received in 2014-10-14, accepted in 2015-05-21,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls.MethodsWe performed two case–control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants.ResultsWe detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005).ConclusionsThese results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.

【 授权许可】

Unknown   
© Cappetta et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.