Pre-eclampsia during pregnancy and risk of endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: Pre-eclampsia may be associated with the development of endometrial cancer; however, previous findings have been conflicting. OBJECTIVES: To investigate if pre-eclampsia is associated with an increased risk of endometrial cancer. METHOD: Two independent reviewers screened titles and abstracts of studies identified in MEDLINE, Embase, and Web of Science databases from inception until March 2022. Studies were included if they investigated pre-eclampsia and subsequent risk of endometrial cancer (or precursor lesions). Random-effects meta-analysis was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between pre-eclampsia during pregnancy and endometrial cancer risk. MAIN RESULTS: There were seven articles identified which investigated endometrial cancer, of which one also investigated endometrial cancer precursors. Overall, the studies include 11,724 endometrial cancer cases. No association was observed between pre-eclampsia and risk of endometrial cancer with moderate heterogeneity observed (pooled HR 1.07, 95% CI 0.79-1.46, I2 = 34.1%). In sensitivity analysis investigating risk of endometrial neoplasia (atypical hyperplasia, carcinoma in situ, or cancer), there was some evidence that pre-eclampsia was associated with an increased risk (HR 1.34, 95% CI 1.15-1.57, I2 = 29.6%). CONCLUSIONS: Pre-eclampsia was not associated with an increased risk of endometrial cancer. Additional large studies with information on pre-eclampsia sub-type aiming to investigate endometrial cancer precursor conditions are merited.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. RESULTS: In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). CONCLUSIONS: We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.