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.

► Cancer gene mutations increase susceptibility to specific environmental carcinogens.
► Formaldehyde is a common environmental carcinogen that causes DNA cross-links.
► Hereditary BRCA1/2 pathway mutations can prevent proper repair of DNA cross-links.
► Mutations cause undue risks for formaldehyde linked cancers such as myeloid leukemia.
► Avoiding specific known carcinogens can reduce cancer risks in mutation carriers.