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

Mónica Cappetta, María Berdasco, Jimena Hochmann, Carolina Bonilla, Mónica Sans, Pedro C. Hidalgo, Nora Artagaveytia, Rick A Kittles, Miguel Martínez, Manel Esteller, Bernardo Bertoni

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Article number434
JournalBMC Cancer
Volume15
Issue number1
DOIs
StatePublished - Dec 12 2015

Fingerprint

DNA Methylation
Leukocytes
Melanoma
Neoplasms
Breast Neoplasms
Epigenomics
Population
Uruguay
North American Indians
Population Genetics
Skin Neoplasms
Tumor Biomarkers
Hispanic Americans
African Americans
Methylation
Case-Control Studies
High Pressure Liquid Chromatography
Genome
Skin
DNA

Keywords

  • Admixture
  • Cancer
  • DNA methylation
  • Genetic ancestry

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Cappetta, M., Berdasco, M., Hochmann, J., Bonilla, C., Sans, M., Hidalgo, P. C., ... Bertoni, B. (2015). Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients. BMC Cancer, 15(1), [434]. https://doi.org/10.1186/s12885-015-1461-0

Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients. / Cappetta, Mónica; Berdasco, María; Hochmann, Jimena; Bonilla, Carolina; Sans, Mónica; Hidalgo, Pedro C.; Artagaveytia, Nora; Kittles, Rick A; Martínez, Miguel; Esteller, Manel; Bertoni, Bernardo.

In: BMC Cancer, Vol. 15, No. 1, 434, 12.12.2015.

Research output: Contribution to journalArticle

Cappetta, M, Berdasco, M, Hochmann, J, Bonilla, C, Sans, M, Hidalgo, PC, Artagaveytia, N, Kittles, RA, Martínez, M, Esteller, M & Bertoni, B 2015, 'Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients', BMC Cancer, vol. 15, no. 1, 434. https://doi.org/10.1186/s12885-015-1461-0
Cappetta M, Berdasco M, Hochmann J, Bonilla C, Sans M, Hidalgo PC et al. Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients. BMC Cancer. 2015 Dec 12;15(1). 434. https://doi.org/10.1186/s12885-015-1461-0
Cappetta, Mónica ; Berdasco, María ; Hochmann, Jimena ; Bonilla, Carolina ; Sans, Mónica ; Hidalgo, Pedro C. ; Artagaveytia, Nora ; Kittles, Rick A ; Martínez, Miguel ; Esteller, Manel ; Bertoni, Bernardo. / Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients. In: BMC Cancer. 2015 ; Vol. 15, No. 1.
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AU - Bonilla, Carolina

AU - Sans, Mónica

AU - Hidalgo, Pedro C.

AU - Artagaveytia, Nora

AU - Kittles, Rick A

AU - Martínez, Miguel

AU - Esteller, Manel

AU - Bertoni, Bernardo

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N2 - 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.

AB - 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.

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