2022年11月9日 / 最終更新日 : 2022年11月22日 ad_y ニュース

2022年 新着論文 36　ゲノム制御学分野から論文が発表されました

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

Cancer Med. 2022 Nov 7. doi: 10.1002/cam4.5430. Online ahead of print.

Authors

Tomoharu Mori  1   2 , Yusuke Okamoto  1 , Anfeng Mu  1 , Yoshimi Ide  3   4 , Akiyo Yoshimura  5 , Noriko Senda  6 , Yukiko Inagaki-Kawata  6 , Masahiro Kawashima  6 , Hiroyuki Kitao  7 , Eriko Tokunaga  8 , Yasuo Miyoshi  9 , Shozo Ohsumi  10 , Koichiro Tsugawa  11 , Tomohiko Ohta  12 , Toyomasa Katagiri  13 , Shigeru Ohtsuru  2 , Kaoru Koike  2 , Seishi Ogawa  14   15   16 , Masakazu Toi  6 , Hiroji Iwata  5 , Seigo Nakamura  4 , Keitaro Matsuo  17   18 , Minoru Takata  1

Affiliations

  • 1 Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
  • 2 Department of Primary Care and Emergency Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 3 Division of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
  • 4 Department of Breast Surgery, Kikuna Memorial Hospital, Yokohama, Japan.
  • 5 Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
  • 6 Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 7 Department of Molecular Cancer Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • 8 Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
  • 9 Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan.
  • 10 Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
  • 11 Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
  • 12 Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan.
  • 13 Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • 14 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 15 Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Solna, Sweden.
  • 16 Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
  • 17 Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
  • 18 Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

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.

Keywords: ALDH2; BRCA1; BRCA2; Fanconi anemia; hereditary breast and ovarian cancer.

© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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