A common environmental carcinogen unduly affects carriers of cancer mutations: Carriers of genetic mutations in a specific protective response are more susceptible to an environmental carcinogen

One way an inherited cancer gene mutation may target specific tissues for cancer is by increasing susceptibility when a tissue is exposed to environmental carcinogens. An example of this may be the increased susceptibility of BRCA1 or BRCA2 mutation carriers to the carcinogen formaldehyde. Formaldehyde is now a proven cause of human myeloid leukemias. Yet millions of tons of formaldehyde are produced every year and it is everywhere. High formaldehyde levels can overwhelm normal enzyme detoxification systems and cause DNA damage. It is known that some types of formaldehyde-associated DNA damage require error-free DNA repairs mediated by pathways containing BRCA1 and BRCA2 proteins. Otherwise some formaldehyde-related DNA damage cannot be properly repaired so mutations may occur. Therefore, carriers of BRCA1 and BRCA2 gene defects should be unduly susceptible to myeloid leukemia. Studies show that inherited biallelic BRCA2 gene defects dramatically increase risks for myeloid leukemia. Heterozygous BRCA1 or BRCA2 mutations also increase risks for myeloid leukemias in 11 of 12 relevant studies. BRCA1/2 mutation carriers may reduce risks for myeloid leukemias by using available precautions to lower their exposure to formaldehyde

Mutations in components of antiviral or microbial defense as a basis for breast cancer

In-depth functional analyses of thousands of breast cancer gene mutations reveals vastly different sets of mutated genes in each of 21 different breast cancer genomes. Despite differences in which genes are mutated, innate immunity pathways and metabolic reactions supporting them are always damaged. These functions depend on many different genes. Mutations may be rare individually but each set of mutations affects some aspect of pathogen recognition and defense, especially those involving viruses. Some mutations cause a dysregulated immune response, which can also increase cancer risks. The frequency of an individual mutation may be less important than its effect on function. This work demonstrates that acquired immune deficiencies and dysregulation in cancer can occur because of mutations. Abnormal immune responses represent a hidden variable in breast cancer - viral association studies. Compensating for these abnormalities may open many new opportunities for cancer prevention and therapy