Metabolic Syndrome and Epigenetic Markers of Breast Cancer in Nigerian Women

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ABSTRACT Developing countries accounted for 45% of new breast cancer cases globally in 2009, and 57% in 2012, with these proportions projected to increase to 70% by 2030. Nigeria has experienced a three-fold increase in breast cancer incidence between 1973 and 2012, coinciding with an increase in the prevalence of so-called `diseases of affluence' including obesity, hypertension, and diabetes, a cluster of biochemical abnormalities that constitute Metabolic Syndrome (MetS). Recent studies in the US and Europe have shown a consistent positive association between MetS and breast cancer risk, suggesting that rising breast cancer rates in Nigeria may be a biological consequence of increasing rates of MetS. Once diagnosed with breast cancer, Nigerian women, similar to other women of African descent, are also more likely to present at younger ages, with highly aggressive, hormone-receptor negative tumors, associated with higher mortality. The reason for a higher prevalence of these tumor types in women of African descent is unclear. Epigenetic changes, through DNA methylation, histone modification and micro RNA changes are critical aspects of breast cancer tumorigenesis, and are influenced by both genetic background and environmental exposures. Multiple US studies have observed significant differences in DNA methylation levels of critical breast cancer genes between African- Americans and whites, including BRCA1 and BRCA2, CYP1A1, H-ras-1, and Cyclin D1. DNA methylation levels in critical breast cancer genes among Nigerian women have never been examined, and this may be the key to understanding racial differences in breast cancer phenotypes. Identification of race-specific epigenetic patterns could potentially be used as an intermediary marker of the association between exposures such as MetS and breast cancer incidence, or as prognostic markers for clinical management and therapeutic interventions. Using a sample of newly diagnosed breast cancer cases and age-matched healthy controls, this study aims to examine the association between MetS and breast cancer overall, and by sub-type in Nigeria. In addition, we plan to identify genome-wide DNA methylation differences between breast cancer tumor and adjacent normal tissue among women with and without MetS. These findings will provide critical information on the influence of MetS on breast cancer in Nigeria, and improve our understanding of the specific epigenetic changes that occur with breast cancer in Nigerian women; this is likely to be different from epigenetic changes observed among African American women with significantly different environmental exposures.