{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:20:25Z","timestamp":1785777625696,"version":"3.56.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi230774-4\"><jats:title>Importance<\/jats:title><jats:p>Research suggests that increased mitochondrial DNA copy number (mtDNAcn) is associated with increased risk of non-Hodgkin lymphoma (NHL); however, no studies to date have evaluated whether the mitochondrial DNA fraction with breaks (mtDNAfb) is associated with risk of NHL.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230774-5\"><jats:title>Objective<\/jats:title><jats:p>To evaluate the association of mtDNAfb with NHL risk.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230774-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This nested case-control study, which used prospectively collected samples as part of baseline enrollment (from 1985 through 1988) of 29\u202f133 men who smoked for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study conducted in southwest Finland, included 107 incident NHL cases and 107 controls (matched on date of birth \u00b15 years). Analyses were conducted from January to September 2022.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230774-7\"><jats:title>Exposure<\/jats:title><jats:p>High-throughput real-time polymerase chain reaction assays quantifying mtDNAfb.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230774-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Incident NHL cases were identified in the ATBC Study through April 30, 2002, using the Finnish Cancer Registry and the Register of Causes of Death. The mtDNAfb was quantified and categorized based on the median, tertile, and quartile distributions among controls. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression models to assess the associations between categorized mtDNAfb and future risk of NHL, controlling for age, body mass index, number of cigarettes smoked per day, number of pack-years, and mtDNAcn.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230774-9\"><jats:title>Results<\/jats:title><jats:p>A total of 29\u202f133 men (median [IQR] age, 57.2 [52.6-62.5] years) participated in ATBC Study. Higher mtDNAfb was associated with an increased risk of NHL (median OR, 2.89; 95% CI, 1.40-5.93) in a dose-dependent manner (quartile 2 vs 1 OR, 1.24; 95% CI, 0.43-3.40; quartile 3 vs 1 OR, 3.58; 95% CI, 1.39-9.24; quartile 4 vs 1 OR, 3.42; 95% CI, 1.30- 8.99; <jats:italic>P<\/jats:italic>\u2009=\u2009.004 for trend).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230774-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This study\u2019s findings suggest that increased mtDNAfb is associated with an increased future risk of NHL. Additional studies are needed to confirm these findings, particularly among women and nonsmokers.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.26885","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T15:02:37Z","timestamp":1690988557000},"page":"e2326885","source":"Crossref","is-referenced-by-count":3,"title":["Mitochondrial DNA Fragmentation and Risk of Non-Hodgkin Lymphoma"],"prefix":"10.1001","volume":"6","author":[{"suffix":"III","given":"H. Dean","family":"Hosgood","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Davitt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Cawthon","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batel","family":"Blechter","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Y.Y.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad L.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satu","family":"M\u00e4nnist\u00f6","sequence":"additional","affiliation":[{"name":"Department of Public Health Promotion, National Institute for Health and Welfare, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrius","family":"Albanes","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Rothman","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lan","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"issue":"3","key":"zoi230774r1","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1158\/1055-9965.431.13.3","article-title":"Non-Hodgkin\u2019s lymphoma and type of tobacco smoke.","volume":"13","author":"Stagnaro","year":"2004","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"6","key":"zoi230774r2","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1093\/aje\/kwu290","article-title":"Associations of non-Hodgkin lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci.","volume":"181","author":"Wang","year":"2015","journal-title":"Am J Epidemiol"},{"issue":"13","key":"zoi230774r3","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1080\/15592294.2022.2115604","article-title":"Epigenome-wide association studies of occupational exposure to benzene and formaldehyde.","volume":"17","author":"Phillips","year":"2022","journal-title":"Epigenetics"},{"issue":"9","key":"zoi230774r4","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1002\/ajim.v63.9","article-title":"Benzene exposure-response and risk of lymphoid neoplasms in Chinese workers: a multicenter case-cohort study.","volume":"63","author":"Linet","year":"2020","journal-title":"Am J Ind Med"},{"issue":"9","key":"zoi230774r5","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1136\/oem.2005.022418","article-title":"Occupational trichloroethylene exposure and non-Hodgkin\u2019s lymphoma: a meta-analysis and review.","volume":"63","author":"Mandel","year":"2006","journal-title":"Occup Environ Med"},{"issue":"2","key":"zoi230774r6","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1289\/ehp.1002318","article-title":"Occupational benzene exposure and the risk of lymphoma subtypes: a meta-analysis of cohort studies incorporating three study quality dimensions.","volume":"119","author":"Vlaanderen","year":"2011","journal-title":"Environ Health Perspect"},{"issue":"10","key":"zoi230774r7","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.1182\/blood-2008-05-157974","article-title":"A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma.","volume":"112","author":"Lan","year":"2008","journal-title":"Blood"},{"issue":"19","key":"zoi230774r8","doi-asserted-by":"publisher","first-page":"8739","DOI":"10.1073\/pnas.91.19.8739","article-title":"Mitochondrial DNA sequence variation in human evolution and disease.","volume":"91","author":"Wallace","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"zoi230774r9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176795","article-title":"Selective mitochondrial DNA degradation following double-strand breaks.","volume":"12","author":"Moretton","year":"2017","journal-title":"PLoS One"},{"key":"zoi230774r10","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1196\/annals.1338.011","article-title":"Mitochondrial genome instability and mtDNA depletion in human cancers.","volume":"1042","author":"Lee","year":"2005","journal-title":"Ann N Y Acad Sci"},{"issue":"6","key":"zoi230774r11","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/CEJ.0b013e32832f9bd6","article-title":"Mitochondrial DNA depletion promotes impaired oxidative status and adaptive resistance to apoptosis in T47D breast cancer cells.","volume":"18","author":"Yu","year":"2009","journal-title":"Eur J Cancer Prev"},{"key":"zoi230774r12","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.chemosphere.2019.02.044","article-title":"Early mitochondrial fragmentation is a potential in vitro biomarker of environmental stress.","volume":"223","author":"Perdiz","year":"2019","journal-title":"Chemosphere"},{"issue":"1","key":"zoi230774r13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/1047-2797(94)90036-1","article-title":"The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance.","volume":"4","author":"The ATBC Cancer Prevention Study Group","year":"1994","journal-title":"Ann Epidemiol"},{"issue":"4","key":"zoi230774r14","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1080\/028418602760169442","article-title":"The Finnish Cancer Registry as follow-up source of a large trial cohort\u2013accuracy and delay.","volume":"41","author":"Korhonen","year":"2002","journal-title":"Acta Oncol"},{"issue":"6","key":"zoi230774r15","first-page":"687","article-title":"Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash.","volume":"10","author":"Garc\u00eda-Closas","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"12","key":"zoi230774r16","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1080\/10715760310001621342","article-title":"Oxidative stress-related alteration of the copy number of mitochondrial DNA in human leukocytes.","volume":"37","author":"Liu","year":"2003","journal-title":"Free Radic Res"},{"key":"zoi230774r17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/978-1-59745-521-3","article-title":"Measuring mtDNA damage using a supercoiling-sensitive qPCR approach.","volume":"554","author":"Chan","year":"2009","journal-title":"Methods Mol Biol"},{"issue":"9","key":"zoi230774r18","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1101\/gad.217778.113","article-title":"The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.","volume":"27","author":"Chan","year":"2013","journal-title":"Genes Dev"},{"issue":"2","key":"zoi230774r19","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.cdp.2003.11.008","article-title":"Large-scale mitochondrial DNA deletion mutations and nuclear genome instability in human breast cancer.","volume":"28","author":"Zhu","year":"2004","journal-title":"Cancer Detect Prev"},{"issue":"3","key":"zoi230774r20","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1023\/A:1027324410022","article-title":"Oxidative damage and fragmentation of mitochondrial DNA in cellular apoptosis.","volume":"17","author":"Ozawa","year":"1997","journal-title":"Biosci Rep"},{"issue":"10","key":"zoi230774r21","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1021\/acs.chemrestox.0c00083","article-title":"Mitochondrial DNA damage: prevalence, biological consequence, and emerging pathways.","volume":"33","author":"Zhao","year":"2020","journal-title":"Chem Res Toxicol"},{"key":"zoi230774r22","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1476-069X-10-63","article-title":"Spatial-temporal analysis of non-Hodgkin lymphoma in the NCI-SEER NHL case-control study.","volume":"10","author":"Wheeler","year":"2011","journal-title":"Environ Health"},{"issue":"4","key":"zoi230774r23","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1159\/000448389","article-title":"Lymph node fine-needle cytology of non-Hodgkin lymphoma: diagnosis and classification by flow cytometry.","volume":"60","author":"Cozzolino","year":"2016","journal-title":"Acta Cytol"},{"issue":"5","key":"zoi230774r24","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1080\/0284186X.2019.1711166","article-title":"Epidemiology of classic and nodular lymphocyte predominant Hodgkin lymphoma in Finland in 1996-2015.","volume":"59","author":"Juntikka","year":"2020","journal-title":"Acta Oncol"},{"issue":"7","key":"zoi230774r25","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1158\/1055-9965.EPI-05-0958","article-title":"Incidence of non-Hodgkin\u2019s lymphoma in Sweden, Denmark, and Finland from 1960 through 2003: an epidemic that was.","volume":"15","author":"Sandin","year":"2006","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"6","key":"zoi230774r26","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1111\/bjh.v189.6","article-title":"Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century\u2014a Swedish lymphoma register study.","volume":"189","author":"Ekberg","year":"2020","journal-title":"Br J Haematol"},{"issue":"11","key":"zoi230774r27","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.3390\/cancers14112710","article-title":"Associations between smoking and alcohol and follicular lymphoma incidence and survival: a family-based case-control study in Australia.","volume":"14","author":"Odutola","year":"2022","journal-title":"Cancers (Basel)"},{"key":"zoi230774r28","doi-asserted-by":"publisher","DOI":"10.1177\/14034948221104351","article-title":"Contribution of smoking change to 45-year trend in prevalence of chronic bronchitis in Finland.","author":"Vartiainen","year":"2022","journal-title":"Scand J Public Health"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2807926\/hosgood_2023_oi_230774_1690380888.0712.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T15:02:40Z","timestamp":1690988560000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2807926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":28,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.26885","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}