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

Persistent Link:
http://hdl.handle.net/10150/610271
Title:
Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients
Author:
Cappetta, Mónica; Berdasco, María; Hochmann, Jimena; Bonilla, Carolina; Sans, Mónica; Hidalgo, Pedro C.; Artagaveytia, Nora; Kittles, Rick; Martínez, Miguel; Esteller, Manel; Bertoni, Bernardo
Affiliation:
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)
Issue Date:
2015
Publisher:
BioMed Central Ltd
Citation:
Cappetta et al. BMC Cancer (2015) 15:434 DOI 10.1186/s12885-015-1461-0
Journal:
BMC Cancer
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)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
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.
EISSN:
1471-2407
DOI:
10.1186/s12885-015-1461-0
Keywords:
Genetic ancestry; DNA methylation; Admixture; Cancer
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2407/15/434

Full metadata record

DC FieldValue Language
dc.contributor.authorCappetta, Mónicaen
dc.contributor.authorBerdasco, Maríaen
dc.contributor.authorHochmann, Jimenaen
dc.contributor.authorBonilla, Carolinaen
dc.contributor.authorSans, Mónicaen
dc.contributor.authorHidalgo, Pedro C.en
dc.contributor.authorArtagaveytia, Noraen
dc.contributor.authorKittles, Ricken
dc.contributor.authorMartínez, Miguelen
dc.contributor.authorEsteller, Manelen
dc.contributor.authorBertoni, Bernardoen
dc.date.accessioned2016-05-20T09:02:47Z-
dc.date.available2016-05-20T09:02:47Z-
dc.date.issued2015en
dc.identifier.citationCappetta et al. BMC Cancer (2015) 15:434 DOI 10.1186/s12885-015-1461-0en
dc.identifier.doi10.1186/s12885-015-1461-0en
dc.identifier.urihttp://hdl.handle.net/10150/610271-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.publisherBioMed Central Ltden
dc.relation.urlhttp://www.biomedcentral.com/1471-2407/15/434en
dc.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)en
dc.subjectGenetic ancestryen
dc.subjectDNA methylationen
dc.subjectAdmixtureen
dc.subjectCanceren
dc.titleEffect of genetic ancestry on leukocyte global DNA methylation in cancer patientsen
dc.typeArticleen
dc.identifier.eissn1471-2407en
dc.contributor.departmentDepartamento de Genética, Facultad de Medicina, Universidad de la Repúblicaen
dc.contributor.departmentCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)en
dc.contributor.departmentSchool of Social and Community Medicine, University of Bristolen
dc.contributor.departmentDepartmamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la Repúblicaen
dc.contributor.departmentCentro Universitario de Tacuarembó, Universidad de la Repúblicaen
dc.contributor.departmentDepartamento Básico de Medicina, Facultad de Medicina, Universidad de la Repúblicaen
dc.contributor.departmentDepartment of Surgery and Public Health, University of Arizonaen
dc.contributor.departmentCátedra de Dermatología, Hospital de Clínicas “Manuel Quintela”, Universidad de la Repúblicaen
dc.contributor.departmentDepartment of Physiological Sciences II, School of Medicine, University of Barcelonaen
dc.contributor.departmentInstitucio Catalana de Recerca i Estudis Avançats (ICREA)en
dc.identifier.journalBMC Canceren
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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