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Exposure to organochlorine compounds increases the risk of suffering colorectal cancer

September 29, 2017

The authors have identified two types of compounds, present in the blood of cancer patients, in double the quantity of the non-affected population undergoing the study. In addition, the researchers studied the mechanism that triggers the disease. They have been able to deduce that these compounds cause genetic alterations in genes such as the K-Ras and the p53, which are involved in other cancers such as breast cancer or cancer of the pancreas.

Colorectal cancer is the third most frequent type of cancer in humans and the second deadliest in industrialised countries. Its causes, however, are not fully understood, but diet is believed to play an important role. It is thought that vegetables, fruit and fibre-rich foods protect against it; fats, red meat, as well as excessive consumption of calories, and obesity increase the risk of developing it.

To better understand the causes, a team of researchers led by Victor Moreno, researcher at the Universitat Aut??noma de Barcelona and The Catalan Institute of Oncology, in collaboration with the CSIC's Environmental Chemistry Group, have published the first work that establishes an association between organochlorine compounds and colorectal cancer. The article has been published in the specialised journal, Environmental Health Perspectives.

The researchers measured the concentration of organochlorines in the blood serum of a group of patients at the Bellvitge Hospital. One hundred and thirty-two of the patients had been diagnosed with the disease and 76 others were admitted for other reasons. The analyses identified two specific organochlorines: PCB 28 and PCB 118, which were found at a concentration double that found in the remaining patients. These substances belong to the PCBs or polychlorinated biphenyls. They are toxic compounds coming from industrial processes, which are absorbed into the body through what we eat.

At the same time, the team studied patients affected by colon cancer and two genes implicated in the cancer's development: the K-Ras oncogene and the P53 tumour suppressing gene. The study of mutations indicated the relationship between exposure to PCBs and the presence of transversion type mutations in both genes. That result reinforces the role of PCBs 18 and 128 as probable causes of the carcinogenic processes in the population studied.

The authors believe that the two compounds' ability to produce mutations lies in their unique shape. They have a flat conformation similar to that of the dioxins, which allows them to initiate a chain of chemical processes that can end in a carcinogenic process. An example of this would be the bonding of the compounds to the aryl hydrocarbon receptor that due to their shape would set off the activation of cellular enzymes that produce reactive oxygen species. The latter are precisely what cause damage to the DNA thereby initiating the carcinogenic process.

In addition, the researchers studied other variables such as food intake to discover whether other factors were involved in increasing the risk. Nevertheless, the results were negative for all groups of foods and only alcohol was seen to be an important risk factor for the population under study.

According to the authors, further studies will need to be done in the future to confirm the results. Those studies would benefit from the inclusion of additional organochlorines, which were not analysed this time, as well as by the inclusion of other compounds associated with cancer such as dioxins and furans.

Organochlorines and colorectal cancer

The organochlorine compounds come from industrial and agricultural uses and are widespread in the environment. Their use has been limited and safety measures for them tightened in the last few years due to their toxic effects in the body. Some of them such as DDT, which was formerly used as an insecticide, have even been prohibited. In spite of that, the organochlorines are persistent contaminants that remain in the environment for long periods of time due to slow degradation. Diet constitutes the main route of entrance to the body. Once in the body, the organism has difficulty metabolising them and they usually become stored in the adipose tissue. That means that their half life within the body is on the order of years or even decades.

Organochlorines are excreted from the body by the intestinal route, either by recently ingested compounds or by others released from the adipose tissue. Faeces remain in the large intestine for 1 or 2 days. That amount of time makes possible an exchange of compounds with the epithelium of the large intestine, which does not occur in any other part of the intestinal tract. Those factors enhance the activity of the organochlorines and explains their possible implication in the appearance of colorectal cancer.

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