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Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development
Kathryn Munn 
,
Rachel Lawrence,
Hasan Haboubi,
Hamsa Naser,
Kate Hurlow,
Ume-kulsoom Shah ,
Lisa Williams,
Sarah Gwynne,
Owen Bodger ,
Jiri Zavadil,
Francois Virard,
shareen Doak,
Laura Thomas ,
Gareth Jenkins
,
Rachel Lawrence,
Hasan Haboubi,
Hamsa Naser,
Kate Hurlow,
Ume-kulsoom Shah ,
Lisa Williams,
Sarah Gwynne,
Owen Bodger ,
Jiri Zavadil,
Francois Virard,
shareen Doak,
Laura Thomas ,
Gareth Jenkins
International Journal of Cancer
Swansea University Authors:
Kathryn Munn , Hamsa Naser, Kate Hurlow, Ume-kulsoom Shah , Owen Bodger , shareen Doak, Laura Thomas , Gareth Jenkins
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© 2026 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License.
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DOI (Published version): 10.1002/ijc.70494
Abstract
We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy v...
| Published in: | International Journal of Cancer |
|---|---|
| ISSN: | 0020-7136 1097-0215 |
| Published: |
Wiley
2026
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71742 |
| first_indexed |
2026-04-14T14:31:34Z |
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| last_indexed |
2026-05-01T07:23:37Z |
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cronfa71742 |
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<?xml version="1.0"?><rfc1807><datestamp>2026-04-30T14:35:57.0485365</datestamp><bib-version>v2</bib-version><id>71742</id><entry>2026-04-14</entry><title>Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development</title><swanseaauthors><author><sid>1c7f25073bd2fc065aa2d9bb54062879</sid><ORCID>0009-0009-0960-6328</ORCID><firstname>Kathryn</firstname><surname>Munn</surname><name>Kathryn Munn</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>29b4023fc506f38e5d235994a50d4471</sid><ORCID/><firstname>Hamsa</firstname><surname>Naser</surname><name>Hamsa Naser</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>2317c8816b5f4a9b9308cdb6de2290c8</sid><ORCID/><firstname>Kate</firstname><surname>Hurlow</surname><name>Kate Hurlow</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>bcef4e069220a4b85f8a2c0cc3059487</sid><ORCID>0000-0002-0594-580X</ORCID><firstname>Ume-kulsoom</firstname><surname>Shah</surname><name>Ume-kulsoom Shah</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>8096440ab42b60a86e6aba678fe2695a</sid><ORCID>0000-0002-4022-9964</ORCID><firstname>Owen</firstname><surname>Bodger</surname><name>Owen Bodger</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>8f70286908f67238a527a98cbf66d387</sid><ORCID/><firstname>shareen</firstname><surname>Doak</surname><name>shareen Doak</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>6f80a1638d852bd88d37afe3aeb2fb62</sid><ORCID>0000-0002-8621-5285</ORCID><firstname>Laura</firstname><surname>Thomas</surname><name>Laura Thomas</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>a44095d26187304e903da7ca778697b6</sid><ORCID>0000-0002-5437-8389</ORCID><firstname>Gareth</firstname><surname>Jenkins</surname><name>Gareth Jenkins</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2026-04-14</date><deptcode>MEDS</deptcode><abstract>We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy volunteers (HVs), GORD, BO and OAC patients, alongside plasma biomarkers of inflammation and oxidative stress. Ex vivo challenge assays assessed lymphocyte responses to hydrogen peroxide (H2O2), vinblastine and the bile acid deoxycholic acid (DCA). Tissue-based NF-κB expression was also correlated with MN levels. OAC patients exhibited significantly elevated MN% compared with HVs (p < 0.001), GORD (p < 0.001) and BO (p = 0.016). OAC lymphocytes showed increased sensitivity to vinblastine relative to HVs (p = 0.025) and GORD patients (p = 0.033). Higher baseline MN% correlated with reduced inducible MN formation following H2O2 or DCA, suggesting altered oxidative stress responses. MN% also associated with plasma 8-OHdG, IL-8 and 2′3′-cGAMP, and with reduced oesophageal tissue IκB, indicating activation of oxidative and cGAS-STING/NF-κB signalling. These findings highlight systemic aneugenic and oxidative stress processes that contribute to lymphocyte MN formation in OAC and suggest that MN% may serve as a minimally invasive indicator of inflammation-linked genomic instability. Further investigation is needed to determine its relevance to OAC progression.</abstract><type>Journal Article</type><journal>International Journal of Cancer</journal><volume>0</volume><journalNumber/><paginationStart/><paginationEnd/><publisher>Wiley</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0020-7136</issnPrint><issnElectronic>1097-0215</issnElectronic><keywords>circulating biomarkers; DNA damage; micronucleus; oesophageal adenocarcinoma; oxidative stress</keywords><publishedDay>25</publishedDay><publishedMonth>4</publishedMonth><publishedYear>2026</publishedYear><publishedDate>2026-04-25</publishedDate><doi>10.1002/ijc.70494</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders>Cancer Research Wales</funders><projectreference/><lastEdited>2026-04-30T14:35:57.0485365</lastEdited><Created>2026-04-14T15:29:51.4103811</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Kathryn</firstname><surname>Munn</surname><orcid>0009-0009-0960-6328</orcid><order>1</order></author><author><firstname>Rachel</firstname><surname>Lawrence</surname><order>2</order></author><author><firstname>Hasan</firstname><surname>Haboubi</surname><order>3</order></author><author><firstname>Hamsa</firstname><surname>Naser</surname><orcid/><order>4</order></author><author><firstname>Kate</firstname><surname>Hurlow</surname><orcid/><order>5</order></author><author><firstname>Ume-kulsoom</firstname><surname>Shah</surname><orcid>0000-0002-0594-580X</orcid><order>6</order></author><author><firstname>Lisa</firstname><surname>Williams</surname><order>7</order></author><author><firstname>Sarah</firstname><surname>Gwynne</surname><order>8</order></author><author><firstname>Owen</firstname><surname>Bodger</surname><orcid>0000-0002-4022-9964</orcid><order>9</order></author><author><firstname>Jiri</firstname><surname>Zavadil</surname><order>10</order></author><author><firstname>Francois</firstname><surname>Virard</surname><order>11</order></author><author><firstname>shareen</firstname><surname>Doak</surname><orcid/><order>12</order></author><author><firstname>Laura</firstname><surname>Thomas</surname><orcid>0000-0002-8621-5285</orcid><order>13</order></author><author><firstname>Gareth</firstname><surname>Jenkins</surname><orcid>0000-0002-5437-8389</orcid><order>14</order></author></authors><documents><document><filename>71742__36649__449feeea75854cb78fd5cbac072cd8b5.pdf</filename><originalFilename>71742.VoR.pdf</originalFilename><uploaded>2026-04-30T14:34:08.6258053</uploaded><type>Output</type><contentLength>1865491</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© 2026 The Author(s). 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2026-04-30T14:35:57.0485365 v2 71742 2026-04-14 Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development 1c7f25073bd2fc065aa2d9bb54062879 0009-0009-0960-6328 Kathryn Munn Kathryn Munn true false 29b4023fc506f38e5d235994a50d4471 Hamsa Naser Hamsa Naser true false 2317c8816b5f4a9b9308cdb6de2290c8 Kate Hurlow Kate Hurlow true false bcef4e069220a4b85f8a2c0cc3059487 0000-0002-0594-580X Ume-kulsoom Shah Ume-kulsoom Shah true false 8096440ab42b60a86e6aba678fe2695a 0000-0002-4022-9964 Owen Bodger Owen Bodger true false 8f70286908f67238a527a98cbf66d387 shareen Doak shareen Doak true false 6f80a1638d852bd88d37afe3aeb2fb62 0000-0002-8621-5285 Laura Thomas Laura Thomas true false a44095d26187304e903da7ca778697b6 0000-0002-5437-8389 Gareth Jenkins Gareth Jenkins true false 2026-04-14 MEDS We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy volunteers (HVs), GORD, BO and OAC patients, alongside plasma biomarkers of inflammation and oxidative stress. Ex vivo challenge assays assessed lymphocyte responses to hydrogen peroxide (H2O2), vinblastine and the bile acid deoxycholic acid (DCA). Tissue-based NF-κB expression was also correlated with MN levels. OAC patients exhibited significantly elevated MN% compared with HVs (p < 0.001), GORD (p < 0.001) and BO (p = 0.016). OAC lymphocytes showed increased sensitivity to vinblastine relative to HVs (p = 0.025) and GORD patients (p = 0.033). Higher baseline MN% correlated with reduced inducible MN formation following H2O2 or DCA, suggesting altered oxidative stress responses. MN% also associated with plasma 8-OHdG, IL-8 and 2′3′-cGAMP, and with reduced oesophageal tissue IκB, indicating activation of oxidative and cGAS-STING/NF-κB signalling. These findings highlight systemic aneugenic and oxidative stress processes that contribute to lymphocyte MN formation in OAC and suggest that MN% may serve as a minimally invasive indicator of inflammation-linked genomic instability. Further investigation is needed to determine its relevance to OAC progression. Journal Article International Journal of Cancer 0 Wiley 0020-7136 1097-0215 circulating biomarkers; DNA damage; micronucleus; oesophageal adenocarcinoma; oxidative stress 25 4 2026 2026-04-25 10.1002/ijc.70494 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) Cancer Research Wales 2026-04-30T14:35:57.0485365 2026-04-14T15:29:51.4103811 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Kathryn Munn 0009-0009-0960-6328 1 Rachel Lawrence 2 Hasan Haboubi 3 Hamsa Naser 4 Kate Hurlow 5 Ume-kulsoom Shah 0000-0002-0594-580X 6 Lisa Williams 7 Sarah Gwynne 8 Owen Bodger 0000-0002-4022-9964 9 Jiri Zavadil 10 Francois Virard 11 shareen Doak 12 Laura Thomas 0000-0002-8621-5285 13 Gareth Jenkins 0000-0002-5437-8389 14 71742__36649__449feeea75854cb78fd5cbac072cd8b5.pdf 71742.VoR.pdf 2026-04-30T14:34:08.6258053 Output 1865491 application/pdf Version of Record true © 2026 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License. true eng http://creativecommons.org/licenses/by/4.0/ |
| title |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development |
| spellingShingle |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development Kathryn Munn Hamsa Naser Kate Hurlow Ume-kulsoom Shah Owen Bodger shareen Doak Laura Thomas Gareth Jenkins |
| title_short |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development |
| title_full |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development |
| title_fullStr |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development |
| title_full_unstemmed |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development |
| title_sort |
Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development |
| author_id_str_mv |
1c7f25073bd2fc065aa2d9bb54062879 29b4023fc506f38e5d235994a50d4471 2317c8816b5f4a9b9308cdb6de2290c8 bcef4e069220a4b85f8a2c0cc3059487 8096440ab42b60a86e6aba678fe2695a 8f70286908f67238a527a98cbf66d387 6f80a1638d852bd88d37afe3aeb2fb62 a44095d26187304e903da7ca778697b6 |
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1c7f25073bd2fc065aa2d9bb54062879_***_Kathryn Munn 29b4023fc506f38e5d235994a50d4471_***_Hamsa Naser 2317c8816b5f4a9b9308cdb6de2290c8_***_Kate Hurlow bcef4e069220a4b85f8a2c0cc3059487_***_Ume-kulsoom Shah 8096440ab42b60a86e6aba678fe2695a_***_Owen Bodger 8f70286908f67238a527a98cbf66d387_***_shareen Doak 6f80a1638d852bd88d37afe3aeb2fb62_***_Laura Thomas a44095d26187304e903da7ca778697b6_***_Gareth Jenkins |
| author |
Kathryn Munn Hamsa Naser Kate Hurlow Ume-kulsoom Shah Owen Bodger shareen Doak Laura Thomas Gareth Jenkins |
| author2 |
Kathryn Munn Rachel Lawrence Hasan Haboubi Hamsa Naser Kate Hurlow Ume-kulsoom Shah Lisa Williams Sarah Gwynne Owen Bodger Jiri Zavadil Francois Virard shareen Doak Laura Thomas Gareth Jenkins |
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International Journal of Cancer |
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2026 |
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0020-7136 1097-0215 |
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10.1002/ijc.70494 |
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Wiley |
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Faculty of Medicine, Health and Life Sciences |
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We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy volunteers (HVs), GORD, BO and OAC patients, alongside plasma biomarkers of inflammation and oxidative stress. Ex vivo challenge assays assessed lymphocyte responses to hydrogen peroxide (H2O2), vinblastine and the bile acid deoxycholic acid (DCA). Tissue-based NF-κB expression was also correlated with MN levels. OAC patients exhibited significantly elevated MN% compared with HVs (p < 0.001), GORD (p < 0.001) and BO (p = 0.016). OAC lymphocytes showed increased sensitivity to vinblastine relative to HVs (p = 0.025) and GORD patients (p = 0.033). Higher baseline MN% correlated with reduced inducible MN formation following H2O2 or DCA, suggesting altered oxidative stress responses. MN% also associated with plasma 8-OHdG, IL-8 and 2′3′-cGAMP, and with reduced oesophageal tissue IκB, indicating activation of oxidative and cGAS-STING/NF-κB signalling. These findings highlight systemic aneugenic and oxidative stress processes that contribute to lymphocyte MN formation in OAC and suggest that MN% may serve as a minimally invasive indicator of inflammation-linked genomic instability. Further investigation is needed to determine its relevance to OAC progression. |
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2026-04-25T07:56:56Z |
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11.10461 |