Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2 ‐mutation carriers

The common ALDH2 variant rs671 severely aggravates DNA repair-deficient disorder Fanconi anemia, and it is expected that breast cancer developed in BRCA1/2 mutation carriers are similarly affected. Now we elucidated this is not the case in the actual patient cohort, highlighting cell type-specific differences in the protection/detoxification mediated by ALDH2. AbstractThe aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that theALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22FANC genes including hereditary breast and ovarian cancer (HBOC) genesBRCA1 andBRCA2. We have previously reported that the progression of FA phenotypes is accelerated with theALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in eitherBRCA1 orBRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-typeBRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that theALDH2 genotypes may impact breast cancer development inBRCA1/2 muta...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: RESEARCH ARTICLE Source Type: research