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2015-05-27

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cc-by (c) Cappetta, Mónica et al., 2015
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/108143

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

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https://doi.org/10.1186/s12885-015-1461-0

Resum

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.

Matèries

Genètica molecular, ADN, Metilació, Leucòcits, Malalts de càncer, Melanoma, Càncer de mama

Matèries (anglès)

Molecular genetics, DNA, Methylation, Leucocytes, Cancer patients, Melanoma, Breast cancer

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Articles publicats en revistes (Ciències Fisiològiques)

Citació

CAPPETTA, Mónica, et al. Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients. BMC Cancer. 2015. Vol. 15, num. 434. ISSN 1471-2407. [consulted: 16 of August of 2026]. Available at: https://hdl.handle.net/2445/108143

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