Biomarkers of Zn status associated to colorectal cancer pathogenesis

Cancer is a leading cause of death in both more and less economically developed countries, particularly in less ones, in which about 82% of the world’s population resides [1]. Colorectal cancer (CRC) is the third most frequent malignant disease [2]. Over the last decade, a whole range of new technologies have been introduced in clinical practice to diagnose and treat the disease, with therapeutic modalities extending to advanced stages of the disease. Nevertheless, prevention undoubtedly remains the key to reducing morbidity and mortality [3]. Variation in international incidence rates [2] suggests that CRC aetiology is influenced by modifiable lifestyle factors, such as diet [4–7]. Beyond their general effects on health, micronutrients in patients with cancer have unique implications because of their potential direct effects on existing cancers, and effects on factors that may influence carcinogenesis, such as immunity and interactions with treatment [8]. Zinc is an essential trace element that participates as cofactor in a large number of intermediary metabolism proteins, in hormone secretion pathways and in different mechanisms of immune defence [9]. Zinc is known to be an essential component in DNA-binding zinc fingers proteins, as well as in copper/zinc superoxide dismutase and in several proteins involved in DNA repair mechanisms. Thus, zinc plays an important role in transcription factors function and, antioxidant defence. Dietary deficiencies in zinc can contribute to single- and double-strand DNA breaks and DNA oxidative modifications that increase the risk for cancer development [10]. It is well known that carcinogenesis is a multistep process in which genetic sequence alterations helped by environmental factors, such as oxidative stress and antioxidant status [11], stimulating the selection and proliferation of malignant clones, eventually leading to the development of a detectable tumor. Furthermore, significant alterations in Zn(II) levels in tissues have previously been reported in patients with various forms of cancer. Moreover, low plasma Zn(II) levels have been observed in patients with cancer of the colon, bronchus or digestive system [12]. Because CRC treatment plan needs to consider nutritional responses towards anti-cancer drugs based on their biological and genetic characteristics, a possible association with zinc in cancer treatment also requires attention. Therefore, in this paper, we analyse the physiological and biological implication of Zn on CRC to provide screening, treatment, and prevention strategies. The analysis of Zn biomarkers levels could provide new biological insights that could be applied in prevention, molecular diagnosis, prognosis and treatment of CRC.

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