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

Tomoharu Mori, Yusuke Okamoto, Anfeng Mu, Yoshimi Ide, Akiyo Yoshimura, Noriko Senda, Yukiko Inagaki-Kawata, Masahiro Kawashima, Hiroyuki Kitao, Eriko Tokunaga, Yasuo Miyoshi, Shozo Ohsumi, Koichiro Tsugawa, Tomohiko Ohta, Toyomasa Katagiri, Shigeru Ohtsuru, Kaoru Koike, Seishi Ogawa, Masakazu Toi, Hiroji IwataSeigo Nakamura, Keitaro Matsuo, Minoru Takata

Research output: Contribution to journalArticlepeer-review

Abstract

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 ALDH2 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 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 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 ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients.

Original languageEnglish
JournalCancer Medicine
DOIs
Publication statusAccepted/In press - 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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