Primary ovarian insufficiency (POI) is defined as primary hypogonadism in women before the age of 40 years. Autoimmune causes, FMR1 premutations, and X chromosome deletions and translocations account for a majority of POI…
Breast cancer is increased in women with primary ovarian insufficiency
Author: Kristina Allen-Brady, Barry Moore, Lauren E Verrilli, Margaret A Alvord, Marina Kern, Nicola Camp, Kristen Kelley, Joseph Letourneau, Lisa Cannon-Albright, Mark Yandell, Erica B Johnstone, Corrine K Welt
Publication: The Journal of Clinical Endocrinology & Metabolism
Publisher: Oxford University Press
Date: 2024-07-12
Abstract
Context
DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk.
Objective
We hypothesized that a subset of women with POI and family members would have increased risk for cancer.
Design
Case-control population-based study using records from 1995 to 2022.
Setting
Two major Utah academic health care systems serving 85% of the state.
Subjects
Women with POI (n = 613) were identified using International Classification of Diseases codes and reviewed for accuracy. Relatives were linked using the Utah Population Database.
Intervention
Cancer diagnoses were identified using the Utah Cancer Registry.
Main Outcome Measures
The relative risk of cancer in women with POI and relatives was estimated by comparison to population rates. Whole genome sequencing was performed on a subset of women.
Results
Breast cancer was increased in women with POI (OR, 2.20; 95% CI, 1.30-3.47; P = .0023) and there was a nominally significant increase in ovarian cancer. Probands with POI were 36.5 ± 4.3 years and 59.5 ± 12.7 years when diagnosed with POI and cancer, respectively. Causal and candidate gene variants for cancer and POI were identified. Among second-degree relatives of these women, there was an increased risk of breast (OR, 1.28; 95% CI, 1.08-1.52; P = .0078) and colon cancer (OR, 1.50; 95% CI, 1.14-1.94; P = .0036). Prostate cancer was increased in first- (OR, 1.64; 95% CI, 1.18-2.23; P = .0026), second- (OR, 1.54; 95% CI, 1.32-1.79; P < .001), and third-degree relatives (OR, 1.33; 95% CI, 1.20-1.48; P < .001).
Conclusion
Data suggest common genetic risk for POI and reproductive cancers. Tools are needed to predict cancer risk in women with POI and potentially to counsel about risks of hormone replacement therapy.