title: Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients.
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.
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. monicac@fmed.edu.uy.
authors.forename: Mónica
authors.initials: M
authors.lastname: Cappetta
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de LLobregat, Barcelona, Catalonia, Spain. mberdasco@idibell.cat.
authors.forename: María
authors.initials: M
authors.lastname: Berdasco
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. jimehoc@hotmail.com.
authors.forename: Jimena
authors.initials: J
authors.lastname: Hochmann
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK. C.bonilla@bristol.ac.uk.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bonilla
authors.affiliation: Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay. mbsans@gmail.com.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sans
authors.affiliation: Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay. drpedro.hidalgo@gmail.com.|Centro Universitario de Tacuarembó, Universidad de la República, Tacuarembó, Uruguay. drpedro.hidalgo@gmail.com.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Hidalgo
authors.affiliation: Departamento Básico de Medicina, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. nartagave@fmed.edu.uy.
authors.forename: Nora
authors.initials: N
authors.lastname: Artagaveytia
authors.affiliation: Department of Surgery and Public Health, University of Arizona, Tucson, USA. rkittles@surgery.arizona.edu.
authors.forename: Rick
authors.initials: R
authors.lastname: Kittles
authors.affiliation: Cátedra de Dermatología, Hospital de Clínicas "Manuel Quintela", Universidad de la República, Montevideo, Uruguay. mmartinezasuaga@gmail.com.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de LLobregat, Barcelona, Catalonia, Spain. mesteller@idibell.cat.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain. mesteller@idibell.cat.|Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. bbertoni@fmed.edu.uy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bertoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005828:Genetics, Population; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma