Gene variant involved in cancer risk and viral resistance

16 April 2014

Genes that combat viral infections have also been shown to be involved in cancer risk.

Some environmental factors that increase cancer susceptibility (eg. smoking) are known to create distinctive ‘signatures’ in cancer cell genomes.
 
A family of enzymes encoded by the APOBEC genes has previously been linked with an apparently important form of cancer associated, genome-wide mutational signature that is present in around half of all cancers (see previous news). The APOBEC enzymes are thought to be involved in the body’s defensive immune responses including antibody production and combatting viral infections. Understanding their role in cancer could be crucial for developing better approaches to prevention and treatment.
 
A specific copy number polymorphism in the APOBEC3A-APOBEC3B gene region on chromosome 22 that effectively deletes the APOBEC3B gene has been associated with an increased risk of breast cancer. Now researchers at the Wellcome Trust Sanger Institute in Cambridge, UK have shown that breast cancer patients who carry one or two germline copies of the APOBEC3B deletion variant have more mutations in the APOBEC genome-wide mutational signatures than breast cancer patients without the deletion variant have.
 
They propose that the APOBEC3B deletion variant increases breast cancer susceptibility via increased APOBEC-dependent mutational processes, though the mechanism for this effect remains unknown.
 
Moreover, gene-environment interactions that influence disease susceptibility are rarely straightforward. In this instance, whilst the deletion variant is present in under 10% of the European population, it is present in around 37% of East Asians and over 90% of Oceanians. This may be because the increased susceptibility to cancer is mitigated by a survival advantage, perhaps via increased resistance to specific infectious agents. If cancer prevention strategies were eventually devised based on reducing the mutational effect of the APOBEC3B deletion variant, care would be needed in some populations to ensure that they did not simultaneously increase susceptibility to infection.