BACKGROUND: The 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: These 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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/610271 |
| Date | January 2015 |
| Creators | Cappetta, Mónica, Berdasco, María, Hochmann, Jimena, Bonilla, Carolina, Sans, Mónica, Hidalgo, Pedro C., Artagaveytia, Nora, Kittles, Rick, Martínez, Miguel, Esteller, Manel, Bertoni, Bernardo |
| Contributors | Departamento de Genética, Facultad de Medicina, Universidad de la República, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), School of Social and Community Medicine, University of Bristol, Departmamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Centro Universitario de Tacuarembó, Universidad de la República, Departamento Básico de Medicina, Facultad de Medicina, Universidad de la República, Department of Surgery and Public Health, University of Arizona, Cátedra de Dermatología, Hospital de Clínicas “Manuel Quintela”, Universidad de la República, Department of Physiological Sciences II, School of Medicine, University of Barcelona, Institucio Catalana de Recerca i Estudis Avançats (ICREA) |
| Publisher | BioMed Central Ltd |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2015 Cappetta et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) |
| Relation | http://www.biomedcentral.com/1471-2407/15/434 |
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