Abstract
Abstract Significant disparities exist in breast cancer among African Americans (AAs) women compared to Caucasians. Even though AAs are less likely to undergo regular mammograms due to access barriers, it is unlikely that differences in screen based detection accounts entirely for outcome disparities. While the current guidelines recommend women begin mammography at age 40 or 50, AA women may be at increased risk for delayed diagnosis since >10% of breast cancer cases in AAs are diagnosed in women younger <40 years compared with 5% of Caucasians. This highlights the importance of defining optimal ethnically appropriate age of screening especially given the disproportionate mortality among younger black women patients. Therefore, an alternative approach using biomarkers should be considered in order to develop ethnically appropriate measures for detecting the disease in the earliest stages. Genomic instability has long been recognized as a major driver of carcinogenesis occurring early on and increasing in complexity with disease progression. However, to date little is known about the underlying mechanisms associated with such instability among the different ethnic groups. In this study we hypothesized that alterations in telomere length and dysfunctional centrosome apparatus are underlying mechanisms associated with ethnic-based genomic instability. We investigated alterations in centrosome apparatus, misaligned chromosomes and spindle angle orientation in AA [HCC 70] and Caucasian [HCC1395] cell lines using confocal microscopy. Our results demonstrated significant differences in structural (30%) and numerical alterations (60%) in centrosome apparatus between AA and Caucasian cell lines (p<0.001). We also noticed a significant increase of misaligned chromosomes (35%) and (68 %) in the metaphase of Caucasians and AA’s respectively (p<0.002). In addition, a significant difference in spindle orientation was observed among AAs and Caucasians suggesting that mitotic phase abnormalities may be, in part, responsible for the underlying genetic instabilities associated with breast cancer. Using ingenuity pathway analysis, we compared gene expressions in both AAs and Caucasian cell lines and observed a significant change in telomerase signaling expression between the cell lines, suggesting a role for telomere lengths in the generation of genetic instability. Together, identifying the specific mechanisms that drive tumorigenesis may provide opportunities for future targeted prevention efforts among high risk cohorts. (This work is supported in part by CA189240) Citation Format: Jose Thaiparambil, Oula Mansour, Susan Haley, Randa EL-Zein. Chromosome instability mechanisms in breast cancer among African Americans and Caucasians [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 511. doi:10.1158/1538-7445.AM2017-511
Published Version
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