Abstract
Worldwide, breast cancer is the most commonly diagnosed cancer among women and is the leading cause of female cancer deaths. Zinc (Zn) functions as an antioxidant and plays a role in maintaining genomic stability. Zn deficiency results in oxidative DNA damage and increased cancer risk. Studies suggest an inverse association between dietary and plasma Zn levels and the risk for developing breast cancer. In contrast, breast tumor biopsies display significantly higher Zn levels compared with normal tissue. Zn accumulation in tumor tissue also correlates with increased levels of Zn importing proteins. Further, aberrant expression of Zn transporters in tumors correlates with malignancy, suggesting that altered metal homeostasis in the breast could contribute to malignant transformation and the severity of cancer. However, studies have yet to link dysregulated Zn transport and abnormal Zn-dependent functions in breast cancer development. Herein, we summarize studies that address the multi-modal role of Zn dyshomeostasis in breast cancer with respect to the role of Zn in modulating oxidative stress, DNA damage response/repair pathways and cell proliferation/apoptosis, and the relationship to aberrant regulation of Zn transporters. We also compare Zn dysregulation in breast tissue to that of prostate, pancreatic and ovarian cancer where possible.
Highlights
Worldwide, breast cancer is the most commonly diagnosed cancer among women and is the leading cause of female cancer deaths [1]
In 2008, women diagnosed with breast cancer accounted for 23%, of total cancer cases, and 14% of total cancer deaths resulted from this cancer [1]
Numerous studies document both molecular and genetic factors as initiators and promoters of breast tissue oncogenesis [2]. Among these categories, deregulated mechanisms contributing to increased oxidative stress and consequent genomic instability play an important role in the development of a variety of human diseases, including breast cancer [3,4]
Summary
Breast cancer is the most commonly diagnosed cancer among women and is the leading cause of female cancer deaths [1]. In 2008, women diagnosed with breast cancer accounted for 23%, of total cancer cases, and 14% of total cancer deaths resulted from this cancer [1] Numerous studies document both molecular and genetic factors as initiators and promoters of breast tissue oncogenesis [2]. Inadequate nutrition translates to dietary deficiencies of key micronutrients that could manifest as increased cellular stress and associated DNA damage [5,6,7] In this regard, Zn is an essential trace element and its functions as an antioxidant and its role in the maintenance of genomic stability have been widely reported [8]. We explore each of these functional categories with regard to our current understanding of the consequences resulting from Zn dysregulation in breast tissues and the development of breast cancer (Figure 1)
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