{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T07:58:32Z","timestamp":1785571112639,"version":"3.56.0"},"reference-count":34,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100006458","name":"children\u2019s hospital of philadelphia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009282","name":"United Mitochondrial Disease Foundation","doi-asserted-by":"publisher","award":["NAMDC Gateway to Mitochondrial Medicine Grant"],"award-info":[{"award-number":["NAMDC Gateway to Mitochondrial Medicine Grant"]}],"id":[{"id":"10.13039\/100009282","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>While somatic mitochondrial dysfunction occurs in diverse cancers, the association between oncogenesis and germline mitochondrial gene pathogenic variants remains unclear. Further, few clinical observations have been reported of cancer occurring in primary mitochondrial disease (PMD) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To improve understanding of the potential modulating role for PMD gene disorders in cancer prevalence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>727 individuals, including 100 with PMD, from 97 unrelated families were retrospectively surveyed to assess their history of individual cancer occurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We evaluated survey responses by characterizing the cancer prevalence among the study cohort and comparing to the general U.S. population via the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database. Odds ratio calculation was performed to determine the association of survey responses and cancer prevalence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Although overall cancer prevalence in PMD probands and their families was elevated compared to the NCI SEER rate (8800 vs 5600 cases per 100,000), odds ratio calculation determined that PMD did not significantly increase the likelihood of developing cancer, with a non-significant trend observed toward less cancer occuring in PMD that needs to be explored in further studies. Cancer prevalence was significantly correlated with advanced age. Significantly reduced prevalence of prostate cancer was seen across the entire cohort. Surprisingly, while low absolute prevalence (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2004=\u20043), a 9-fold increased odds ratio of cancer was seen in\n                      <jats:italic toggle=\"yes\">POLG<\/jats:italic>\n                      patients relative to those with other causes of PMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>No evidence of increased cancer odds was identified in a cohort of PMD patients and their close relatives. Interestingly, a possible inverse association, which did not reach statistical significance, was suggested between mitochondrial disease status and cancer odds. Future prospective investigations in larger PMD kindreds are warranted to validate and evaluate potential mechanistic relations between cancer prevalence and PMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/26330040261471914","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:05:11Z","timestamp":1785326711000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer prevalence in primary mitochondrial disease patients and their families"],"prefix":"10.1177","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1035-6704","authenticated-orcid":false,"given":"Shrey","family":"Dalwadi","sequence":"first","affiliation":[{"name":"Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Division of Genetic and Genomic Medicine, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-1664","authenticated-orcid":false,"given":"Colleen C.","family":"Muraresku","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7451-5117","authenticated-orcid":false,"given":"Kelsey","family":"Keith","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen D.","family":"Valverde","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Nathanson","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marni J.","family":"Falk","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine Frontier Program, Division of Genetic and Genomic Medicine, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia, ARC 1002c, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.80"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3038"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3365"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146610"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40142-018-0138-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1482"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021220"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24362"},{"key":"e_1_3_4_10_2","volume-title":"GeneReviews (Internet) University of Washington","author":"Chinnery P.","year":"1993","unstructured":"Chinnery P. Mitochondrial disorders overview, 2000 (updated 2010). GeneReviews (Internet) University of Washington, Seattle WA, 1993."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209607"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-2220"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3275"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e3181ef42c1"},{"key":"e_1_3_4_15_2","first-page":"477","article-title":"Increased prevalence of malignancy in adult mitochondrial disorders","volume":"6","author":"Finsterer J","year":"2013","unstructured":"Finsterer J, Krexner E. Increased prevalence of malignancy in adult mitochondrial disorders. J Med Life 2013; 6: 477.","journal-title":"J Med Life"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.66"},{"key":"e_1_3_4_17_2","article-title":"Hepatectomy for liver metastasis from rectal cancer in a patient with mitochondrial disease","volume":"14","author":"Takei S","year":"2021","unstructured":"Takei S, Homma Y, Matsuyama R, et al. Hepatectomy for liver metastasis from rectal cancer in a patient with mitochondrial disease. BMJ Case Reports CP 2021; 14: e238653.","journal-title":"BMJ Case Reports CP"},{"key":"e_1_3_4_18_2","first-page":"1","article-title":"First cases of MPV17 related mitochondrial DNA depletion syndrome with compound heterozygous mutations in p. R50Q\/p. R50W: a case report","volume":"6","author":"Umetsu S","year":"2020","unstructured":"Umetsu S, Inui A, Kobayashi S, et al. First cases of MPV17 related mitochondrial DNA depletion syndrome with compound heterozygous mutations in p. R50Q\/p. R50W: a case report. Hepatoma Res 2020; 6: 1.","journal-title":"Hepatoma Res"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197513"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310408"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823a0c7f"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61602-X"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/opo.12131"},{"key":"e_1_3_4_25_2","unstructured":"Surveillance Research Program NCI. SEER*Explorer: an interactive website for SEER cancer statistics. 2024 Apr 17 ed.: SEER Incidence Data November 2023 Submission (1975-2021) SEER 22 registries 2024."},{"key":"e_1_3_4_26_2","first-page":"741","article-title":"Mitochondrial disorders","volume":"118","author":"Klopstock T","year":"2021","unstructured":"Klopstock T, Priglinger C, Yilmaz A, et al. Mitochondrial disorders. Deutsches \u00c4rzteblatt International 2021; 118: 741.","journal-title":"Deutsches \u00c4rzteblatt International"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12185"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-145"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06203-2"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0264-z"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24185"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10091838"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2009.71"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139846"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27665"}],"container-title":["Therapeutic Advances in Rare Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/26330040261471914","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/26330040261471914","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/26330040261471914","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T07:46:23Z","timestamp":1785570383000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/26330040261471914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":34,"alternative-id":["10.1177\/26330040261471914"],"URL":"https:\/\/doi.org\/10.1177\/26330040261471914","relation":{},"ISSN":["2633-0040","2633-0040"],"issn-type":[{"value":"2633-0040","type":"print"},{"value":"2633-0040","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"article-number":"26330040261471914"}}