{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T01:28:20Z","timestamp":1771550900039,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["kakenhi"],"award-info":[{"award-number":["kakenhi"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JPJSCCA20200009"],"award-info":[{"award-number":["JPJSCCA20200009"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The 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 the <jats:italic>ALDH2<\/jats:italic> 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\u2010defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 <jats:italic>FANC<\/jats:italic> genes including hereditary breast and ovarian cancer (HBOC) genes <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic>. We have previously reported that the progression of FA phenotypes is accelerated with the <jats:italic>ALDH2<\/jats:italic> rs671 genotype. Individuals with HBOC are heterozygously mutated in either <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic>, and the cancer\u2010initiating cells in these patients usually undergo loss of the wild\u2010type <jats:italic>BRCA1\/2<\/jats:italic> allele, leading to homologous recombination defects. Therefore, we hypothesized that the <jats:italic>ALDH2<\/jats:italic> genotypes may impact breast cancer development in <jats:italic>BRCA1\/2<\/jats:italic> mutant carriers. We genotyped <jats:italic>ALDH2<\/jats:italic> in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the <jats:italic>ALDH2<\/jats:italic> genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of <jats:italic>ALDH2<\/jats:italic> function in cancer initiation and development in breast epithelium of HBOC patients.<\/jats:p>","DOI":"10.1002\/cam4.5430","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T05:39:21Z","timestamp":1667885961000},"page":"6594-6602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lack of impact of the <scp>ALDH2<\/scp> rs671 variant on breast cancer development in Japanese <scp>BRCA1<\/scp>\/2\u2010mutation carriers"],"prefix":"10.1002","volume":"12","author":[{"given":"Tomoharu","family":"Mori","sequence":"first","affiliation":[{"name":"Laboratory of DNA Damage Signaling, Department of Late Effects Studies Radiation Biology Center Graduate School of Biostudies, Kyoto University  Kyoto Japan"},{"name":"Department of Primary Care and 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