FEMALES with primary ovarian insufficiency (POI), experiencing menopause at ≤40 years, face a heightened risk for breast cancer, and a slightly elevated risk for ovarian cancer, according to new research.
The study reviewed data from 613 females with POI and 165 females who experienced early menopause (41–44 years), utilising medical records from 1995–2022 from the University of Utah, Salt Lake City, USA, and Intermountain Healthcare systems. Females with conditions like oophorectomy, Turner syndrome, or previous chemotherapy or radiation were excluded. Kristy Allen-Brady, University of Utah School of Medicine, who presented the findings at the Endocrine Society (ENDO) 2024 Annual Meeting, noted the comprehensive nature of the study: “These two healthcare systems serve 85% of Utah’s population, effectively making this a population study.”
Using genealogy information from the Utah Population Database and cancer diagnoses from the Utah Cancer Registry, researchers estimated the relative cancer risk among females with POI and their relatives compared to the general population. They found that females with POI had a two-fold increased risk for breast cancer, with 18 observed cases versus the expected eight (risk ratio [RR]: 1.89; 95% confidence interval [CI]: 1.20–2.84; P=0.0056). The risk for ovarian cancer was also higher, but not statistically significant.
Incorporating data from females who experienced early menopause, the study confirmed a significant risk for breast cancer (RR: 1.9; 95% CI: 1.2–2.8; P=0.7) and ovarian cancer (RR: 3.4; 95% CI: 1.2–8.6; P=0.03). Relatives of females with POI also exhibited increased cancer risks. Second-degree relatives had higher risks for breast (RR:1.28; 95% CI: 1.08–1.71; P=0.0078) and colon cancer (RR: 1.5; 95% CI: 1.14–1.94; P=0.0036). Prostate cancer risks were elevated among first-, second-, and third-degree relatives.
“There appears to be a common genetic risk factor for both POI and hormonally influenced cancers,” stated Allen-Brady. Through next-generation sequencing, the team identified harmful variants in genes responsible for DNA damage repair and transcription fidelity in females with POI. This discovery suggests a genetic predisposition to both POI and reproductive cancers, extending to their family members.
Future research may focus on using next-generation sequencing to identify females at risk for both POI and cancer, and counselling for hormone replacement therapy should consider these genetic risks, Allen-Brady suggested.
Reference
Allen-Brady KL et al. OR25-04. ENDO annual meeting, 1-4 June, 2024.
