Epithelial cancers in the post-genomic era: should we reconsider our lifestyle?

• Published in: Cancer and metastasis reviews 2013-12, Vol.32 (3-4), p.673-705
• Main Authors: Holly, Jeff M. P., Zeng, Li, Perks, Claire M.
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Carcinogens; Comorbidity; Development and progression; Disease Progression; Environment; Epidemiology; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genetic aspects; Genomics; Humans; Life Style; Mutation; Neoplasm Metastasis; Neoplasms, Glandular and Epithelial - epidemiology; Neoplasms, Glandular and Epithelial - etiology; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - pathology; Non-Thematic Review; Oncology; Oncology, Experimental; Phosphatidylinositol 3-Kinases - metabolism; Physiological aspects; Signal Transduction
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-013-9445-5

The age-related epithelial cancers of the breast, colorectum and prostate are the most prevalent and are increasing in our aging populations. Epithelial cells turnover rapidly and mutations naturally accumulate throughout life. Most epithelial cancers arise from this normal mutation rate. All elderly individuals will harbour many cells with the requisite mutations and most will develop occult neoplastic lesions. Although essential for initiation, these mutations are not sufficient for the progression of cancer to a life-threatening disease. This progression appears to be dependent on context: the tissue ecosystem within individuals and lifestyle exposures across populations of individuals. Together, this implies that the seeds may be plentiful but they only germinate in the right soil. The incidence of these cancers is much lower in Eastern countries but is increasing with Westernisation and increases more acutely in migrants to the West. A Western lifestyle is strongly associated with perturbed metabolism, as evidenced by the epidemics of obesity and diabetes: this may also provide the setting enabling the progression of epithelial cancers. Epidemiology has indicated that metabolic biomarkers are prospectively associated with cancer incidence and prognosis. Furthermore, within cancer research, there has been a rediscovery that a switch in cell metabolism is critical for cancer progression but this is set within the metabolic status of the host. The seed may only germinate if the soil is fertile. This perspective brings together the different avenues of investigation implicating the role that metabolism may play within the context of post-genomic concepts of cancer.