Cancer prevalence in primary mitochondrial disease patients and their families

作者：Shrey Dalwadi, Nicole Engelhardt, Colleen Muraresku, Kelsey Keith, Kathleen Valverde, Katherine L. Nathanson, Marni J. Falk · 发表于：Therapeutic Advances in Rare Disease · 年份：2026 · DOI：10.1177/26330040261471914 · 研究领域：Mitochondrial Function and Pathology、GDF15 and Related Biomarkers、ATP Synthase and ATPases Research

Background: 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. Objectives: To improve understanding of the potential modulating role for PMD gene disorders in cancer prevalence. Design: 727 individuals, including 100 with PMD, from 97 unrelated families were retrospectively surveyed to assess their history of individual cancer occurrence. Methods: 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. Results: 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...