Recent cancer studies, performed by a group of scientific researchers at the Wellcome Trust Sanger Institute, United Kingdom, suggest the genetic origins of cancer.
Cancer is caused by a disruption in the regular base sequence of the cell’s genetic makeup. Typically, many of these mutations need to occur before the cell begins to proliferate uncontrollably, ultimately, resulting in tumor formation. Normal cells have control mechanisms to reign in such division, but these processes become impaired during cancer.
There are three types of genes that are responsible for encouraging cancer, including tumor suppressor genes, oncogenes and DNA repair genes. Oncogenes, when mutated or expressed to a high degree, cause the cell to divide uncontrollably. Normally, tumor suppressor genes prohibit the development of tumors by regulating cell division; once again, however, if these regulatory genes are mutated, this can also lead to uncontrolled cellular proliferation.
Finally, DNA repair genes often instigate changes that fix damage to the cell’s genetic makeup. If these genes are disrupted, as with tumor suppressor genes, this can lead to an elevation in the total number of mutations present, again, leading to cancer development.
These mutations are caused by a number of factors. Oftentimes, the replication process is imperfect, and can lead to a few harmless genetic changes; this does not usually lead to cancer, as at least half a dozen mutations are necessitated to turn the cell into a cancerous state. Even when this does occur, the cell possesses mechanisms to deal with this eventuality, terminating itself during a biological process called apoptosis.
However, genetic predisposition, exposure to radiation and carcinogens, aging, obesity and even infection are all factors that have been linked to cancer.
Investigating over 7,000 individual genome samples, representing 30 different types of cancer (including brain, breast and lung cancers), the study was able to identify and map trademark signs of mutation. There were 21 characteristic alterations in the genetic sequence of the various DNA samples, which were present across 97% of the cancer-causing mutations.
The conclusions of the study were revealing. As we are already well aware, different cancers are the sum result of a host of different biological aberrations. The origins of breast cancer are very different to that of ovarian cancer, as an example. The team established that ovarian cancer was provoked by two mutational mechanisms, whereas liver cancer was the result of three times as many mutational mechanisms.
The scientists also established a commonality amongst different cancers, where a particular mutational process would be involved in different types of cancer. This was not always the case, however, as a number of mutations were condition-specific (e.g. some neuroblastoma and stomach mutations), and were only witnessed within this particular form of cancer.
In addition, out of all the 30 cancer types investigated, 20 of them encompassed at least one mutation related to aging.
The study also delved into the role of one of the body’s natural defense mechanisms, a category of enzymes called APOBEC. These protein-based structures, under normal conditions, repel viral infection by disrupting their genetic material. According to the group, APOBEC enzymes 1, 3A and 3B are likely involved in certain cancers, as they cause unintended changes to the host’s genetic sequences when directed against viral pathogens.
Ultimately, the study goes a long way to explaining some of the basic genetic changes that transpire during cancer formation. It is plausible that these data could pinpoint treatment and prevention strategies in the future, whilst additional research into cancer mapping could also help with understanding the true, genetic origins of cancer.
By: James Fenner