Posted on September 11, 2014
From Richards’s Review this week, I highlight the resurrection of the BCG vaccine and the new gene on the block in the world of breast cancer.
In the BMJ’s article, “Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis” by Roy et al. we are told that the BCG vaccine DOES in fact protect children from developing M. tuberculosis AND slows the progression of the disease.
Tuberculosis (TB) is an infection caused by the bacteria Mycobacterium tuberculosis. TB is most known for attacking the lungs, where it causes individuals to develop a chronic bloody cough, weight loss and night sweats. This is called the active phase of the disease. Some people get infected with M. tuberculosis, but don’t develop any of the symptoms and are NOT infectious. This is called latent TB. About 10% of people who have latent TB that are not treated go on to develop the active disease.
Previously, it was not able to demonstrate whether the BCG vaccine prevents acquisition of the infection or rather only limits the progression of the infection to disease. (Important to remind everyone at this point that just because you can be colonised with an organism, does not mean you are infected!) The reason for this is because previous studies used the tuberculin skin test, which was unable to differentiate between individuals who had the disease or had merely taken the vaccine. However, in the past decade a new test has been developed called the T cell based Interferon-γ release assay (IGRA), this meta analysis only uses studies using IGRA. The study reports that the BCG vaccine reduced infection by 19-27% and reduced progression to active TB by 71%.
The BCG vaccine does work, not as effectively as other vaccines, but works none the less. BCG vaccination should have a part in immunisation programmes, but further work is needed to improve its efficacy.
PS. Check out the responses to the BMJ article for some very interesting debates on association vs causation.
In the NEJM’s article, “Breast-Cancer Risk in Families with Mutations in PALB2”, we are introduced to the new kid on the block in terms of cancer genes. Although less infamous than the BRCA2 mutations, PALB2 mutations carry a very similar risk in the development of breast cancer.
PALB2 gene is responsible for creating a protein that helps repair double stranded DNA. Normally in our cells, mistakes in writing our DNA happen all the time. However, we have failsafe mechanisms in place to fix these mistakes before they can cause any trouble, one of the proteins that assist in their repair is encoded by the PALB2 gene, thus making it a tumour suppressor gene. So when a mutation occurs in this gene, the DNA repairing gene never gets made (or is made incorrectly), which results in more and more errors in the DNA… Ultimately, this is what leads to the development of cancer.
Individuals who are PALB2 mutation carriers have approximated 8x higher risk of developing breast cancer. The cumulative risk of developing breast cancer was 35% by 70 years old.
PALB2 is an important gene in the development of breast cancer. Due to the high risk of developing cancer, screening for PALB2 should be considered alongside with BRCA1 and BRCA2.