title: Hypertensive disorders of pregnancy and subsequent risk of solid cancer--A nationwide cohort study.
abstract: Women with hypertensive disorders of pregnancy (HDP) have higher levels of antiangiogenic growth factors during pregnancy than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, we hypothesized that women with a history of HDP might have a reduced risk of solid cancers (cancers other than lymphomas, hematologic cancers and nonmelanoma skin cancers) later in life. In a register-based cohort study of 1.08 million women giving birth at least once between 1978 and 2011, we used Cox regression to estimate hazard ratios (HRs) comparing solid cancer rates for women with and without a history of HDP. In this cohort, 68,236 women (6.3%) had ≥1 pregnancy complicated by HDP and 42,236 women (3.9%) developed solid tumors during follow-up. A history of HDP was not associated with a clinically meaningful reduction in the overall rate of solid cancer (HR 0.96, 95% confidence interval 0.92-1.00), regardless of HDP severity or time since HDP, nor was there a general tendency toward reduced solid cancer rates across organ sites. A history of HDP was only significantly associated with decreased rates of breast and lung cancers and with increased rates of endometrial and urinary tract cancers. Overall, our results do not support the hypothesis that women with a history of HDP have a reduced overall risk of solid cancer due to a persistent post-HDP antiangiogenic state or an innate tendency toward antiangiogenesis. Observed associations with specific cancers may instead be due to other pregnancy-related mechanisms or to residual/unmeasured confounding.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Behrens
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Saima
authors.initials: S
authors.lastname: Basit
authors.affiliation: Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Jensen
authors.affiliation: Department of Obstetrics, Rigshospitalet (Copenhagen University Hospital), Copenhagen, Denmark.
authors.forename: Jacob Alexander
authors.initials: JA
authors.lastname: Lykke
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Lars Peter
authors.initials: LP
authors.lastname: Nielsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.affiliation: Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.|Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjær
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.|Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Heather Allison
authors.initials: HA
authors.lastname: Boyd
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology* / Q000473:pathology; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000150:complications / Q000453:epidemiology* / Q000473:pathology; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors
keywords: angiogenesis; cancer; epidemiology; hypertensive disorders of pregnancy