Fight Aging!

Here, researchers find an unrelated mechanism by which an immune response to invading viruses might as a side-effect damage DNA in cells, and thus raise the risk of certain types of cancer. Both bacterial and viral infections of various types have been linked to increased cancer risk. There is no doubt a diverse set of mechanisms yet to be discovered that might explain these correlations. You might recall a recent paper suggesting that some bacteria force a more rapid pace of replication in stem cells, boosting the occurrence of mutational damage as a result, for example. That is very different from the mechanism uncovered in this research, and we might expect other mechanisms to be equally varied.

Infection with human papilloma virus (HPV) is the primary cause of cervical cancer and a subset of head and neck cancers worldwide. A new paper describes a fascinating mechanism that links these two conditions - viral infection and cancer. The link, basically, is a family of enzymes called APOBEC3. These APOBEC3 enzymes are an essential piece of the immune system's response to viral infection, attacking viral DNA to cause disabling mutations. Unfortunately, the action of family member APOBEC3A can spill over from its attack against viruses to induce DNA mutations and damage in the host genome as well. In other words, this facet of the immune system designed to scramble viral DNA can scramble human DNA as well, sometimes in ways that cause cancer.

"We know that the majority of cancers are caused by genetic mutations. And we know some of the mechanisms that cause these mutations, for example UV radiation can cause mutations that lead to skin cancer and smoking can cause mutations that lead to lung cancer. But there are many more cancers in which we don't know the source of the mutations. The APOBEC3 family can explain how some of these mutations are created. In fact, APOBEC3A can be activated in many ways - not just with HPV infection - and its action may drive a percentage of oncogenic mutations across many cancer types."

Data from the Cancer Genome Atlas showed signatures of APOBEC3-mediated mutations in the PIK3CA gene of about 40 percent of HPV-positive head and neck cancers, but only about 10 percent of HPV-negative head and neck cancers. Adding to this storyline of APOBEC3A-mediated oncogenesis was the fact that expression of APOBEC3A was much higher in HPV-positive cancers. Interestingly, this system that so heavily risks damaging host DNA doesn't work so well against its intended target - APOBEC3A does not successfully eliminate the HPV virus, which remains as a chronic infection. "We have another paper from 2015 showing that HPV has revised their genome against this APOBEC3 enzyme, altering and reducing the target sequences in their own DNA. If APOBEC3 fails to recognize its target sequence, it does not interrupt the DNA. In this, we can see the complex race of evolution - the host evolves the APOBEC3 system to target viruses, but then the viruses evolve their DNA to evade APOBEC3. We are not at any endpoint of evolution - what we may be seeing is the our body's attempt to use this APOBEC3 system to help it evolve more quickly in response to the virus."

Link: http://www.coloradocancerblogs.org/hand-immune-system-can-also-cause-cancer/