Genes, cancer and the environment
Genes, the environment, and the interaction between them produce the state of health or disease in which patients find themselves. Genetic predisposition to a disease means that the individual is not born with a disease, but has a high risk of acquiring it if pathological activity of the relevant gene network is provoked. Most often, it is the environmental influences on gene activity that trigger a person’s health status from being ‘at risk’ to diseased.
In many cancers for example, individuals are born with genes that may function normally for most of their lives. When triggered by certain lifestyle habits, infection or environmental cues, the activity of these genes can turn pathological and contribute significantly to carcinogenesis. Two things underlie this process: genome instability and inflammation. Genome instability accelerates the dysfunction of genetic activity while inflammation fosters the microenvironment necessary for cancer hallmarks to thrive.
The hallmarks of cancer are well described. They include sustaining growth signalling, evading apoptosis and tumour suppressors, and potentiating pluripotency, angiogeneis, invasion and metastasis. These hallmarks result from the mutation of some genes and consequent deregulation of others. In the new era of molecular medicine, it is possible to detect very early deregulation of gene networks that are responsible for malignant growth. Using latest molecular techniques, the early detection of cancer can now happen at unprecedented early stages of malignancy.
Molecular technology is now at the forefront of enabling personalised medicine. In cancer, molecular testing can be performed on tumour tissue or on Circulating Tumour Cells (CTCs), the metastasising population of tumour cells in the blood stream. Early detection of cancer through CTC sampling and genetic analysis allows clinicians to detect pathological change in gene activity at the molecular level. For example, we can now detect when inflammatory-regulators NFB or TGF- have transitioned from functioning in their healthy physiological capacity, to being deregulated. Deregulated NFB and TGF- networks foster the cancer stem cell niche and potentiate progression to malignancy. Monitoring the expression patterns of these and other oncogenes in individuals who are at risk is revolutionising personalised cancer management. Through such monitoring, clinicians can evaluate treatment success in real-time and design individualised cancer treatment plans.
Networks of gene interactions are highly complex. There are multitudes of feedback loops, co- and self-regulatory mechanisms that work together in controlling gene expression. The environment plays just as crucial a role as genes themselves in determining the outcome of gene activity. The clinician’s task is to make sense of the complex array of information that is now available to us. The future of molecular genetic testing that has been alluded to in the past decade is now the present. Monitoring disease-risk genes that are continuously affected by the external and internal environment is integral to the future of preventative medicine.