Abstract
Acute hepatic porphyria (AHP) is considered to be a risk factor for primary liver cancer (PLC), but varying risk estimates have been published. Our aim was to investigate the risk of PLC and other cancers in persons with AHP using a nationwide cohort design. Given that greater numbers of women than men tend to have manifest and more severe AHP, a further aim was to investigate sex differences in this risk. The study sample consisted of all Norwegian residents aged 18 years or older during the period 2000-2011. Persons with AHP (n = 251) were identified through the Norwegian Porphyria Centre, and patients with a cancer diagnosis were identified by linkage to the Cancer Registry of Norway. For persons with AHP, the annual incidence rate of PLC was 0.35%. PLC risk was substantially higher for individuals with an AHP diagnosis compared to the reference population [adjusted hazard ratio (aHR) 108, 95% confidence interval (CI) 56-207]. In a meta-analysis of published studies on PLC and AHP, including ours, women had a higher risk than men. In addition, our results suggested that persons with AHP may have increased risks of kidney (aHR 7.4, 95% CI 2.4-23.1) and endometrial cancers (aHR 6.2, 95% CI 2.0-19.3). Our findings confirmed a substantially higher risk of PLC associated with AHP compared to the general population. In a meta-analysis, the risk was shown to be greater for women than men. The novel findings of a moderate to substantial association between AHP and kidney and endometrial cancers should be investigated further.
Highlights
The porphyrias comprise of several rare metabolic disorders in which a crucial enzymatic step in the biosynthesis of haem is affected, mostly due to a genetic defect
Persons with porphyria cutanea tarda (PCT) and acute hepatic porphyria (AHP) are at substantially increased risk of hepatocellular carcinoma (HCC) compared to the general population
Lifestyle factors likely contribute to these observations in persons with PCT, something specific about PCT itself may contribute to the pathophysiology of HCC
Summary
The porphyrias comprise of several rare metabolic disorders in which a crucial enzymatic step in the biosynthesis of haem is affected, mostly due to a genetic defect. The laboratory diagnosis and specialised treatment of the porphyrias have received a great deal of attention over the past three decades This has led to marked improvements in health, especially concerning acute attacks of acute hepatic porphyria (AHP). Each type is caused by a specific deficiency of an enzyme involved in the eight steps of haem bio-synthesis (Figure 1) [1] This altered activity of an enzyme can lead to the accumulation of the haem precursors 5-aminolaevulinic acid (ALA), porphobilinogen (PBG), and/or porphyrins in individuals with porphyria, which can have diverse acute and chronic clinical effects [2]. Symptoms of the disorders can present as acute attacks of abdominal pain and neurovisceral symptoms (acute intermittent porphyria (AIP)), cutaneous symptoms (porphyria cutanea tarda (PCT), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP) and X-linked erythropoietic protoporphyria (XLEPP)) or both (hereditary coproporphyria (HCP) and variegate porphyria (VP))
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