Everyday Chemicals Have Potential to Cause Cancer
Chemicals are everywhere, in our cosmetics, foods, clothing and furniture. They are known as aldehydes and can interfere with DNA repair, resulting in the development of cancer.
A new study suggests that aldehyde exposure impedes DNA repair, even in normal healthy cells, but people who have inherited a faulty copy of the BRCA2 are particularly sensitive to such damage. The study led by Ashok Venkitaraman, ph.D., director of the Medical Research Council Cancer Unit at the University of Cambridge, and colleagues used genetically engineered human cells and cell from patients bearing a faulty copy of the breast cancer gene BRCA2 to identify the mechanism by which exposure to aldehydes could promote cancer.
Damage to our DNA arises when our cells divide, and it can lead to the development of cancers. Although the body has its own defence mechanism that helps repair this damage, it is obstructed by chemicals of the aldehyde class.
The work appeared on 1 June in the Cell journal, in an article entitled, “A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability.” The article explains that exposure to naturally occurring concentrations of formaldehyde or acetaldehyde selectively unmasks genomic instability in cells heterozygous for multiple, clinically relevant, truncating BRCA2 mutations.
The authors commented, “Naturally occurring concentrations of formaldehyde, a product of cellular metabolism and a ubiquitous environmental toxin, provoke replication fork instability and structural chromosomal aberrations in cells heterozygous for multiple, pathogenic truncating mutations affecting the BRCA2 tumour suppressor. These anomalies arise from a previously unrecognized effect of formaldehyde to selectively deplete BRCA2 via proteasomal degradation. Similar effects occur with acetaldehyde, a product of ethanol catabolism.”
The findings could help explain why people who inherit a single faulty copy of the BRCA2 gene are susceptible to cancer. Cells should be able to repair DNA using the lower, but still adequate levels of BRCA2 protein made from the remaining intact copy of the gene. But unfortunately, this doesn’t always happen.
The study went on to divulge that aldehydes trigger the degradation of BRCA2 protein in cells. In people who inherit one faulty copy of the BRCA2 gene, this effect pushes down BRCA2 protein levels below the amount required for adequate DNA repair, breaking down the normal mechanisms that prevent mutations, which could promote cancer formation. The authors of the Cell article speculate that BRCA2 inactivation triggers spontaneous mutagenesis during DNA replication via aberrant RNA-DNA hybrids (R-loops).
“Our study shows how chemicals to which we are increasingly exposed in our day to day lives, may increase the risk of diseases like cancer,” added Venkitaraman. “It also helps to explain why ‘the fault in our stars’ – namely, the faulty genes we are born with – could make some people particularly sensitive to the cancer-causing effects of these chemicals.
“An important implication of our work is that it may be aldehyde exposure that triggers cancer susceptibility in people who inherit one faulty copy of the BRCA2 gene. This may help us in future to prevent or treat cancer in such people.”
This new research shows that aldehyde accumulation in those who inherit the faulty ALDH2 gene, that inactivates the enzyme known as acetaldehyde dehydrogenase, could trigger cancer susceptibility by degrading BRCA2, compromising DNA repair, whether or not they inherit a faulty copy of BRCA2. An estimated 30% to 60% of people from Japan, Korea, and China carry the faulty ALDH2 and may, therefore, be at risk from cancer through this new mechanism.
The authors concluded, “Epidemiological studies seem warranted to investigate the risk of cancer associated with BRCA2 mutations in such populations, particularly in light of the difficulty in testing these hypotheses in genetically engineered pre-clinical mouse models. Conversely, it is tempting to speculate that dietary supplementation with formaldehyde scavengers like Resveratrol may offer a future strategy to reduce cancer incidence in patients who carry pathogenic truncating mutations affecting BRCA2.“