Genotype and Associated Cancer Risk in Individuals With Telomere Biology Disorders

作者：Marena R. Niewisch, Jung Kim, Neelam Giri, Judith C. Lunger, Lisa J. McReynolds, Sharon A. Savage · 发表于：JAMA Network Open · 年份：2024 · DOI：10.1001/jamanetworkopen.2024.50111 · 被引用次数：17 · 研究领域：Telomeres, Telomerase, and Senescence、Nuclear Structure and Function、Genetic factors in colorectal cancer

Importance: Telomere biology disorders (TBDs) are inherited cancer-prone bone marrow failure syndromes with differences in morbidity and mortality based on mode of inheritance. Objective: To quantify cancer risks in TBDs by genetic subgroups. Design, Setting, and Participants: This longitudinal cohort study of TBDs assessed cancer occurrences from 2002 through 2022. Participants were individuals with a TBD-associated pathogenic germline variant recruited across institutions by self-referral. Data were collected and analyzed through June 30, 2022. Exposures: The exposure was TBD genotypes, with subgroups defined by inheritance pattern (autosomal-dominant [AD-non-TINF2] vs autosomal-recessive/X-linked [AR/XLR] vs AD-TINF2). Main Outcomes and Measures: The main outcome was cancer; secondary outcomes included death, or organ transplant. Cumulative cancer incidence was determined considering death or transplant as competing events. Observed:expected (O:E) ratios of cancer before and after any organ transplant were calculated using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Results: Among 230 individuals with TBD (135 [58.7%] male; median [range] age at last follow-up, 34.6 [1.4-82.2] years) included, the risk of cancer was 3-fold higher than the general population (O:E, 3.35 [95% CI, 2.32-4.68]). The highest risk was observed in individuals with AR/XLR (O:E, 19.16 [95% CI, 9.19-35.24]) with a significantly younger cancer onset than in indi...