Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients

Mingzhu Sun; Jayne Moquet; Michele Ellender; Simon Bouffler; Christophe Badie; Rachel Baldwin-Cleland; Kevin Monahan; Andrew Latchford; David Lloyd; Susan Clark; Nicola A. Anyamene; Elizabeth Ainsbury; David Burling

doi:10.1007/s10689-022-00299-9

Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients

Mingzhu Sun^*, Jayne Moquet, Michele Ellender, Simon Bouffler, Christophe Badie, Rachel Baldwin-Cleland, Kevin Monahan, Andrew Latchford, David Lloyd, Susan Clark, Nicola A. Anyamene, Elizabeth Ainsbury, David Burling

^*Corresponding author for this work

UK Health Security Agency

Research output: Contribution to journal › Review article › peer-review

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Abstract

The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.

Original language	English
Pages (from-to)	61-70
Number of pages	10
Journal	Familial Cancer
Volume	22
Issue number	1
Early online date	20 Jun 2022
DOIs	https://doi.org/10.1007/s10689-022-00299-9
Publication status	Published - Jan 2023

Bibliographical note

Funding Information: This work was partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Chemical and Radiation Threats and Hazards, a partnership between UKHSA and Imperial College London. The views expressed are those of the authors and not necessarily those of the NIHR, UKHSA or the Department of Health and Social Care.

Open Access: This 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/.

Publisher Copyright: © Crown 2022.

Citation: Sun, M., Moquet, J., Ellender, M. et al. Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients. Familial Cancer 22, 61–70 (2023). https://doi.org/10.1007/s10689-022-00299-9

DOI: https://doi.org/10.1007/s10689-022-00299-9

Keywords

DNA mismatch repair deficiency
Familial colorectal cancer
Ionizing radiation
Lynch syndrome
Radio-sensitivity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Sun, M., Moquet, J., Ellender, M., Bouffler, S., Badie, C., Baldwin-Cleland, R., Monahan, K., Latchford, A., Lloyd, D., Clark, S., Anyamene, N. A., Ainsbury, E., & Burling, D. (2023). Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients. Familial Cancer, 22(1), 61-70. https://doi.org/10.1007/s10689-022-00299-9

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title = "Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients",

abstract = "The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.",

keywords = "DNA mismatch repair deficiency, Familial colorectal cancer, Ionizing radiation, Lynch syndrome, Radio-sensitivity",

author = "Mingzhu Sun and Jayne Moquet and Michele Ellender and Simon Bouffler and Christophe Badie and Rachel Baldwin-Cleland and Kevin Monahan and Andrew Latchford and David Lloyd and Susan Clark and Anyamene, {Nicola A.} and Elizabeth Ainsbury and David Burling",

note = "Funding Information: This work was partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Chemical and Radiation Threats and Hazards, a partnership between UKHSA and Imperial College London. The views expressed are those of the authors and not necessarily those of the NIHR, UKHSA or the Department of Health and Social Care. Open Access: This 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/. Publisher Copyright: {\textcopyright} Crown 2022. Citation: Sun, M., Moquet, J., Ellender, M. et al. Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients. Familial Cancer 22, 61–70 (2023). https://doi.org/10.1007/s10689-022-00299-9 DOI: https://doi.org/10.1007/s10689-022-00299-9",

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Sun, M, Moquet, J , Ellender, M , Bouffler, S , Badie, C, Baldwin-Cleland, R, Monahan, K, Latchford, A, Lloyd, D, Clark, S, Anyamene, NA, Ainsbury, E & Burling, D 2023, 'Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients', Familial Cancer, vol. 22, no. 1, pp. 61-70. https://doi.org/10.1007/s10689-022-00299-9

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AU - Bouffler, Simon

AU - Badie, Christophe

AU - Baldwin-Cleland, Rachel

AU - Monahan, Kevin

AU - Latchford, Andrew

AU - Lloyd, David

AU - Clark, Susan

AU - Anyamene, Nicola A.

AU - Ainsbury, Elizabeth

AU - Burling, David

N1 - Funding Information: This work was partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Chemical and Radiation Threats and Hazards, a partnership between UKHSA and Imperial College London. The views expressed are those of the authors and not necessarily those of the NIHR, UKHSA or the Department of Health and Social Care. Open Access: This 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/. Publisher Copyright: © Crown 2022. Citation: Sun, M., Moquet, J., Ellender, M. et al. Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients. Familial Cancer 22, 61–70 (2023). https://doi.org/10.1007/s10689-022-00299-9 DOI: https://doi.org/10.1007/s10689-022-00299-9

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N2 - The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.

AB - The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.

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Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients

Abstract

Bibliographical note

Keywords

UN SDGs

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