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Environmental impact on carcinogenesis under BRCA1 haploinsufficiency
Cancer is the primary cause of human mortality in Japan since 1981. Although numerous novel therapies have been developed and applied in clinics, the number of deaths from cancer is still increasing worldwide. It is time to consider the strategy of cancer prevention more seriously. Here we propose a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837898/ https://www.ncbi.nlm.nih.gov/pubmed/36639692 http://dx.doi.org/10.1186/s41021-023-00258-5 |
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author | Toyokuni, Shinya Kong, Yingyi Motooka, Yashiro Akatsuka, Shinya |
author_facet | Toyokuni, Shinya Kong, Yingyi Motooka, Yashiro Akatsuka, Shinya |
author_sort | Toyokuni, Shinya |
collection | PubMed |
description | Cancer is the primary cause of human mortality in Japan since 1981. Although numerous novel therapies have been developed and applied in clinics, the number of deaths from cancer is still increasing worldwide. It is time to consider the strategy of cancer prevention more seriously. Here we propose a hypothesis that cancer can be side effects of long time-use of iron and oxygen and that carcinogenesis is an evolution-like cellular events to obtain “iron addiction with ferroptosis-resistance” where genes and environment interact each other. Among the recognized genetic risk factors for carcinogenesis, we here focus on BRCA1 tumor suppressor gene and how environmental factors, including daily life exposure and diets, may impact toward carcinogenesis under BRCA1 haploinsufficiency. Although mice models of BRCA1 mutants have not been successful for decades in generating phenotype mimicking the human counterparts, a rat model of BRCA1 mutant was recently established that reasonably mimics the human phenotype. Two distinct categories of oxidative stress, one by radiation and one by iron-catalyzed Fenton reaction, promoted carcinogenesis in Brca1 rat mutants. Furthermore, mitochondrial damage followed by alteration of iron metabolism finally resulted in ferroptosis-resistance of target cells in carcinogenesis. These suggest a possibility that cancer prevention by active pharmacological intervention may be possible for BRCA1 mutants to increase the quality of their life rather than preventive mastectomy and/or oophorectomy. |
format | Online Article Text |
id | pubmed-9837898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98378982023-01-14 Environmental impact on carcinogenesis under BRCA1 haploinsufficiency Toyokuni, Shinya Kong, Yingyi Motooka, Yashiro Akatsuka, Shinya Genes Environ Review Cancer is the primary cause of human mortality in Japan since 1981. Although numerous novel therapies have been developed and applied in clinics, the number of deaths from cancer is still increasing worldwide. It is time to consider the strategy of cancer prevention more seriously. Here we propose a hypothesis that cancer can be side effects of long time-use of iron and oxygen and that carcinogenesis is an evolution-like cellular events to obtain “iron addiction with ferroptosis-resistance” where genes and environment interact each other. Among the recognized genetic risk factors for carcinogenesis, we here focus on BRCA1 tumor suppressor gene and how environmental factors, including daily life exposure and diets, may impact toward carcinogenesis under BRCA1 haploinsufficiency. Although mice models of BRCA1 mutants have not been successful for decades in generating phenotype mimicking the human counterparts, a rat model of BRCA1 mutant was recently established that reasonably mimics the human phenotype. Two distinct categories of oxidative stress, one by radiation and one by iron-catalyzed Fenton reaction, promoted carcinogenesis in Brca1 rat mutants. Furthermore, mitochondrial damage followed by alteration of iron metabolism finally resulted in ferroptosis-resistance of target cells in carcinogenesis. These suggest a possibility that cancer prevention by active pharmacological intervention may be possible for BRCA1 mutants to increase the quality of their life rather than preventive mastectomy and/or oophorectomy. BioMed Central 2023-01-13 /pmc/articles/PMC9837898/ /pubmed/36639692 http://dx.doi.org/10.1186/s41021-023-00258-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Toyokuni, Shinya Kong, Yingyi Motooka, Yashiro Akatsuka, Shinya Environmental impact on carcinogenesis under BRCA1 haploinsufficiency |
title | Environmental impact on carcinogenesis under BRCA1 haploinsufficiency |
title_full | Environmental impact on carcinogenesis under BRCA1 haploinsufficiency |
title_fullStr | Environmental impact on carcinogenesis under BRCA1 haploinsufficiency |
title_full_unstemmed | Environmental impact on carcinogenesis under BRCA1 haploinsufficiency |
title_short | Environmental impact on carcinogenesis under BRCA1 haploinsufficiency |
title_sort | environmental impact on carcinogenesis under brca1 haploinsufficiency |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837898/ https://www.ncbi.nlm.nih.gov/pubmed/36639692 http://dx.doi.org/10.1186/s41021-023-00258-5 |
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