Risk of ovarian cancer in women with pelvic inflammatory disease and homologous recombination repair gene mutations under 55: a population-based cohort study

Area of Science:

• Oncology
• Epidemiology
• Genetics

Background:

• Pelvic inflammatory disease (PID) is a significant gynecological condition.
• Ovarian cancer (OC) remains a leading cause of cancer-related mortality.
• Genetic factors, particularly germline homologous recombination repair (gHR) mutations, influence cancer risk.

Purpose of the Study:

• To investigate the association between PID and OC risk.
• To explore the interplay between PID, genetic vulnerability (gHR mutations), and OC risk.
• To utilize UK Biobank data for a large-scale prospective cohort study.

Main Methods:

• Prospective cohort study design within the UK Biobank.
• Tracking OC incidence in individuals with and without a history of PID.
• Identifying gHR mutation carriers (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1) using whole-exome sequencing data.
• Employing Cox regression models to calculate Hazard Ratios (HRs) for OC risk.

Main Results:

• An overall adjusted HR for OC in patients with PID was 1.45 (95% CI=0.90, 2.32).
• A positive association between PID history and OC risk was observed in individuals under 55 years old (HR=1.92; 95% CI=1.02, 3.63).
• Individuals under 55 with both PID history and gHR mutations showed the highest OC risk (HR=7.40; 95% CI=1.03, 53.10).

Conclusions:

• A significant association exists between PID and OC risk, particularly in women under 55.
• The combination of PID history and gHR mutations confers the highest OC risk.
• PID may act as a precursor to OC, emphasizing the need for early intervention in younger individuals with gHR mutations.