Challenges In The Primary Prevention Of Ovarian Cancer: The Tubal Origin Hypothesis

Kezia GAITSKELL, University of Oxford, United Kingdom
GREEN J. 1 , GATHANI T. 1,2 , COFFEY K. 1 , PIRIE K. 1 , REEVES G. 1 , AHMED A. 3 , BARNES I. 1 , BERAL V. 1

1 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, UK
2 Department of Oncoplastic Breast Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
3 Nuffield Department of Obstetrics and Gynaecology and the Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK

Purpose
Several organisations have recently recommended prophylactic opportunistic bilateral salpingectomy, with ovarian conservation, to reduce ovarian cancer risk. This recommendation is based on molecular and histological studies suggesting a tubal origin of high-grade serous ovarian cancer, together with epidemiological evidence of reduced ovarian cancer risk following tubal sterilization.
Methods
Using Cox regression models, we estimated relative risks (RRs) of different histotypes of ovarian and of other cancers amongst women with versus without tubal sterilization in a large prospective study of UK women, adjusted for potential confounders.
Results
In 1,278,783 women without previous cancer, 8,035 ovarian cancers accrued during 13.8 years’ follow-up. Tubal sterilization was associated with a reduction in overall risk of ovarian cancer (RR=0.80, 95% CI: 0.76-0.85). Risk varied significantly by ovarian cancer histotype (heterogeneity: p<0.001); for the most common serous tumours, risks were significantly lower (p=0.01) for high-grade (RR=0.80, 0.70-0.91; n=1,682) than low-grade tumours (RR=1.12, 0.89-1.42; n=447); risks were halved for endometrioid (RR=0.45, 0.34-0.59; n=590) and clear cell tumours (RR=0.55, 0.39-0.77; n=401); mucinous tumour risk was not reduced (RR=0.99, 0.84-1.18; n=836). Tubal sterilization was also associated with significant reductions for peritoneal (RR=0.81, 0.66-0.98; n=730) and fallopian tube cancers (RR=0.60, 0.37-0.96; n=168).
Conclusions
Our results confirm that tubal sterilization is associated with a reduced risk of certain ovarian cancer histotypes, and of peritoneal and fallopian tube cancers, consistent with hypotheses that many of these have shared origins in the fallopian tube. Opportunistic prophylactic salpingectomy may reduce ovarian cancer risk, but is an untested primary prevention strategy.
Funding source
The Million Women Study is funded by Cancer Research UK (grant no. C570/A16491), the UK Medical Research Council (grant no. MR/K02700X/1), and the National Health Service Breast Screening Programme. KG is supported by Cancer Research UK grant number C38302/A17318, through a CRUK Oxford Centre Clinical Research Training Fellowship.