Germline landscape of high grade serous ovarian cancer across age groups: Is age just a number? Journal Article
| Authors: | Sia, T. Y.; Moufarrij, S.; Milani, J.; Kane, S.; Zhou, Q.; Fong, C.; Khurram, A.; Kemel, Y. M.; Sheehan, M.; Latham, A.; Carlo, M. I.; Murciano-Goroff, Y. R.; Banaszak, L. G.; Abbass, M.; Offit, K.; Iasonos, A.; Roche, K. L.; Chi, D. S.; Mandelker, D.; Aghajanian, C.; Abu-Rustum, N. R.; Stadler, Z. K.; Tew, W. P.; Lichtman, S. M.; Liu, Y. L. |
| Article Title: | Germline landscape of high grade serous ovarian cancer across age groups: Is age just a number? |
| Abstract: | Objective: To characterize age-related variations in germline pathogenic variants (gPVs) in patients with high-grade serous ovarian cancer (HGSOC). Methods: Patients with HGSOC who underwent clinical tumor-normal sequencing of ≥76 genes from 1/1/2015–11/15/2022, were included. Clinical variables including age at diagnosis were collected. Logistic regression models were built to examine associations between gPV, age, and clinical variables. Results: Of 1231 patients, median age at diagnosis was 63 years (range, 33–93); 163 patients (13 %) were diagnosed at age ≤ 49, 739 (60 %) between ages 50–69, and 329 (27 %) at age ≥ 70 years. gPVs were observed in 68 (42 %), 200 (27 %), and 52 patients (16 %) respectively, p < 0.001. Compared to patients diagnosed between ages 50–69, those diagnosed at age ≥ 70 were less likely to have a gPV (OR: 0.58; 95 % CI: 0.38–0.86) and those diagnosed at age ≤ 49 were more likely to have a gPV (OR: 1.78; 95 % CI: 1.18–2.68), after adjustment for genetic ancestry and NCI Comorbidity Index. Seven of 67 patients (10 %) diagnosed at age ≥ 80 years had a gPV, including 2 in OC-related genes (BRCA2, PALB2). Twelve of 21 patients (57 %) diagnosed at age ≤ 39 years had a gPV, all in OC-related genes. No differences in genetics follow-up or poly (ADP-ribose) polymerase inhibitor use were observed by age (p > 0.05). Conclusion: Although gPV rates varied by age with the highest rates observed in patients with early-onset OC, rates were high (≥10 %) in all age groups, with similar genetics follow-up and implementation of targeted therapies. Universal genetic testing is important for all patients with OC regardless of age. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adult; controlled study; aged; middle aged; unclassified drug; gene sequence; major clinical study; comparative study; outcome assessment; follow up; genetic analysis; ovarian cancer; germline; disease association; ovary cancer; clinical assessment; genetic association; genetic variability; brca2 protein; retrospective study; groups by age; age; comorbidity; atm protein; genetic screening; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein msh6; mismatch repair protein pms2; genetic testing; genetic counseling; rates; ancestry group; very elderly; human; female; article; social determinants of health; mutl protein homolog 1; high grade serous ovarian cancer; dna mismatch repair protein msh2; partner and localizer of brca2; regression model; pathogenic variants; brip1 protein; ercc3 protein; rtel1 protein |
| Journal Title: | Gynecologic Oncology |
| Volume: | 201 |
| ISSN: | 10956859 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-10-01 |
| Start Page: | 60 |
| End Page: | 68 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2025.08.016 |
| PUBMED: | 40812120 |
| PROVIDER: | scopus |
| PMCID: | PMC12418476 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Ying L.Liu -- Source: Scopus |
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