TY - JOUR
T1 - Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2-mutation carriers
AU - Mori, Tomoharu
AU - Okamoto, Yusuke
AU - Mu, Anfeng
AU - Ide, Yoshimi
AU - Yoshimura, Akiyo
AU - Senda, Noriko
AU - Inagaki-Kawata, Yukiko
AU - Kawashima, Masahiro
AU - Kitao, Hiroyuki
AU - Tokunaga, Eriko
AU - Miyoshi, Yasuo
AU - Ohsumi, Shozo
AU - Tsugawa, Koichiro
AU - Ohta, Tomohiko
AU - Katagiri, Toyomasa
AU - Ohtsuru, Shigeru
AU - Koike, Kaoru
AU - Ogawa, Seishi
AU - Toi, Masakazu
AU - Iwata, Hiroji
AU - Nakamura, Seigo
AU - Matsuo, Keitaro
AU - Takata, Minoru
N1 - Funding Information:
We thank the patients and family members who have agreed to participate in this study. The authors thank Professor Ashok Venkitaraman for sharing unpublished results and discussion; Ms. Masami Tanaka and Kumi Johchi for technical and secretarial assistance; and Ms. Erin Norah Corrigan Alvi for English editing. This work is also supported by the JSPS Core‐to‐Core Program (Grant #JPJSCCA20200009).
Publisher Copyright:
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
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U2 - 10.1002/cam4.5430
DO - 10.1002/cam4.5430
M3 - Article
AN - SCOPUS:85141464914
JO - Cancer Medicine
JF - Cancer Medicine
SN - 2045-7634
ER -
