Endometrial (uterine) cancer is the most common and second deadliest female reproductive cancer among women in the U.K., with an estimated 9,000 new cases, and 2,200 deaths in 2014. Ovarian cancer is less common but is the deadliest female reproductive cancer, with 7,284 new cases and 4,128 deaths estimated in the U.K. in 20142. Unlike most cancers, the rates of new cases and deaths from endometrial cancer are increasing, and increasing obesity rates may be a major cause of these trends. Obesity is known to put women at risk for endometrial cancer, and may also increase the risk for certain types of ovarian cancer. Conditions related to obesity, such elevated blood pressure and cholesterol, and diabetes, may increase the risk for developing endometrial and ovarian cancer. A better understanding of this biology has generated interest in evaluating whether medications that are prescribed to treat obesity-related conditions could potentially decrease the risk for endometrial and ovarian cancers. This study will explore the relationships between medications commonly prescribed for treatment of these conditions, such as statins and metformin, with risk of endometrial and ovarian cancer in a large health record database with highly accurate and complete diagnostic and drug prescribing data.
Endometrial cancer is the most common gynaecological cancer among women in the U.K., with 9,000 cases, and 2,200 deaths in 2014. Though less common, ovarian cancer is the deadliest gynaecological cancer, with 7,284 cases and 4,128 deaths estimated in 20142. Obesity and related metabolic conditions such as insulin resistance, hypertension, and dyslipidaemia are risk factors for endometrial cancer, and may also be associated with certain types of ovarian cancer. Mechanisms underlying these associations may involve perturbations in several biological pathways, including sex steroid hormone, insulin and insulin-like growth factor (IGF-1), and pro-inflammatory cytokine (e.g., tumour necrosis factor alpha (TNFα) and interleukin-6 (IL-6)) signaling. Pharmacologic antagonism of these pathways may have unanticipated beneficial effects in relation to endometrial and ovarian carcinogenesis. This hypothesis has led to growing interest in evaluating (i.e., “repositioning”) these medications, with the goal of identifying novel molecular targets for pharmacological interventions. We propose to investigate the associations of common medications prescribed to treat metabolic conditions and cardiovascular disease, specifically: statins, metformin, non-selective beta-blockers, and cardiac glycosides, with risk of endometrial and ovarian cancer in a large, longitudinal primary care database known for highly accurate and complete diagnostic and drug prescribing data.
Endometrial Cancer
• Ovarian Cancer
Nicolas Wentzensen - Chief Investigator - National Cancer Institute ( NCI )
Megan Clarke - Corresponding Applicant - National Cancer Institute ( NCI )
Britton Trabert - Collaborator - National Cancer Institute ( NCI )
Kara Michels - Collaborator - National Cancer Institute ( NCI )
Marie Bradley - Collaborator - Food and Drug Administration - FDA
Ruth Pfeiffer - Collaborator - National Cancer Institute ( NCI )
Sarah Irvin - Collaborator - National Cancer Institute ( NCI )
Shahinaz Gadalla - Collaborator - National Cancer Institute ( NCI )
Tamara Litwin - Collaborator - National Cancer Institute ( NCI )
HES Admitted Patient Care;NCRAS Cancer Registration Data;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;Pregnancy Register