31 July 2015
Scientists from the IMPPC, the ICO and the CSIC-UAM show how the natural brakes on the inflammatory process are removed in colorectal tumours
It is now common knowledge that inflammation is involved in many chronic diseases that develop with age, including cancer. We also know that increased inflammation is associated with risk factors such as a high fat diet, smoking and chronic infection, but we don't know exactly how one thing leads to the other. This study fills in the next small part of the whole puzzle.
Colorectal cancer is one of the most common cancers when considering women and men together. It is also one of those that responds best to treatment and is relatively easy to diagnose, despite this, cases are increasing according to Cancer Research UK. Cells in the colon undergo a series of changes as they become cancerous; some of these are errors in the genetic code and others are mediated by other substances attaching to the DNA, altering its behaviour and affecting which genes are active. Inflammation is definitely involved in this process and can also be an indicator that metastasis will occur or of which patients will fare worse, so it is important to better understand the relationship between inflammation and cancer.
In cells a group of molecules called prostanoids control inflammation through a complex chain of reactions; they can both increase and decrease it, acting as both accelerator and brake and maintaining a delicate balancing act. This study shows that in tumour tissues, and most probably in pre-cancerous tissues, the genes that control the braking mechanism are switched off, which leads to a dramatic increase in the levels of inflammation.
In this study samples were taken from tumours and from apparently healthy tissue from the bowel in the same patient. These were also compared with samples from bowel tissue of healthy individuals. For the first time several elements from the prostanoid pathway were studied in relation to each other and whether they were affected by a very typical mechanism for switching genes off called methylation, which effectively "blocks" genes. Results showed pro- and anti-inflammatory signals in the cancer patient’s bowel, indicating that cells were responding to stress. In the cancer tissues, methylation was indeed inactivating the part of the mechanism that reduces inflammation allowing it to increase in an uncontrolled manner, which means it could be used as a way to predict that a tumour might develop in the future. There is also evidence that this pathway is implicated in resistance to chemotherapy, meaning that a study of each patient could provide information as to which treatments would be suitable in each case.
Aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to reduce inflammation and also to reduce the risk of colorectal cancer and improve the outcome for patients who have developed the disease. These drugs have unpleasant side effects such as haemorrhagic strokes or gastrointestinal complications, but drugs that act on specific elements of the prostanoid pathway could prove to be safer and provide more efficient and specific treatments in the future.
It is not yet clear whether the inflammation is a cause or effect of cells turning cancerous. Neither do we know exactly how factors such as smoking, diet or chronic infection, which are associated with higher risks of colorectal cancer, interact with these mechanisms within cells. The scientists who carried out this study recommend more integrated studies that include not only the genetic information and the mechanisms that affect it, but also information about diet and lifestyle. This is just the type of study that the IMPPC is promoting in the GCAT Project, which promises to provide information about how genes and environment interact.