Long-term clinical and socioeconomic consequences of porphyria
Long-term clinical and socioeconomic consequences of the porphyrias
In the previous year, the first article for the project entitled "Acute Hepatic Porphyria and Cancer Risk: A Population-Based Cohort Study' has been submitted. The article is currently under peer review for the journal 'Hepatology'. The first draft of the second article is in progress.
Study one: Acute Hepatic Porphyria and Cancer Risk: A Population-Based Cohort Study. Background. Acute hepatic porphyria (AHP) is considered to be a risk factor for primary liver cancer (PLC), but widely varying risk estimates have been published. Our aim was to investigate the risk of PLC and other cancers in people with AHP using a population-based cohort design and given that greater numbers of women than men tend to have manifest and more severe AHP, we further aimed to investigate sex differences in this risk by meta-analysis of published studies. Methods and findings 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, while patients with a cancer diagnosis were identified by linkage to the Cancer Registry of Norway. For people with AHP, the incidence rate of primary liver cancer (PLC) was 3.5 and 6.3 per 1,000 persons per year, for all participants and for those 50 years or older, respectively. PLC risk was substantially higher for people with an AHP diagnosis compared to the reference population (= 18 years: HR=108, 95% confidence interval (CI): 55-205. In a meta-analysis of previous epidemiological studies, including ours, women had a higher risk of PLC than men (females: HR=130, 95% CI 91-184; males: HR=51, 95% CI 37-71). In addition, exploratory analyses also suggested that people with AHP may have increased risks of kidney (HR=7.4, 95% CI 2.4-23.1) and endometrial cancers (HR=6.2, 95% CI 2.0-19.3). Conclusions. Our findings confirm a substantially higher excess risk of PLC associated with AHP compared with the general population, with estimates being higher than what mostly has been published previously. When pooling all published data, the risk is shown to be greater for women than men. The novel findings of a moderate association between AHP and kidney and endometrial cancers should be investigated further. Thisw study has been submitted to the Journal Hepatology and is currently under peer review. Study two: Porphyria Cutanea Tarda and Cancer Risk. As is the same with the AHP disorders, Porphyria Cutanea Tarda (PCT) is strongly associated with primary liver cancer. However, unlike AHP, PCT is also strongly associated with common primary liver cancer risk factors. Therefore, it remains controversial if the risk of primary liver cancer in people with PCT is greater than the risk associated with these risk factors alone. Studies further suggest that people with PCT may be at a higher risk of lymphoma and lung cancer. Study two will investigate the risk of people with a diagnosis of PCT of developing a primary liver cancer, or another diagnostic specific cancer, relative to the general population. In this study participants with a PCT diagnosis and aged 16 years or older will comprise the exposed group. They will be compared to the general population (Reference), statistically controlling for age, birth cohort, sex and education. Risk will be estimated from the hazard ratios .The clinical characteristics of people with PCT and primary liver cancer will be explored, including if the disease is sporadic or familial and if People With PCT have higher urniary Levels of total porphyrins than other persons With PCT and without cancer. The first draft and analysis of this article is in development.
Cancer and acute hepatic porphyria are associated: a population-based cohort study
The first planned publication for the project was to investigate the risk of people with acute hepatic porphyria of developing primary liver cancer and/or other cancers, compared to the general Norwegian population. To date, all analyses have been completed and a first draft of the manuscript has been prepared.
Acute hepatic porphyria (AHP) consists of a sub-group of rare autosomal dominant diseases. It has been proposed that abnormal heme metabolism in People With AHP may be carcinogenic and increase cancer risk. To date several studies have found a strong Association between AHP and primary liver cancer (PLC). However, the size of the risk is uncertain, with average risk estimates ranging widely. The current study aimed to investigate the incidence and risk of cancers (outcome) in people with a diagnosis of AHP (exposure) using a nationwide population-based cohort design. Age and sex related differences were also investigated. Data from the Norwegian Porphyria Registry was linked with the Cancer Registry of Norway and several other national registries. There were 260 participants with AHP and the reference population consisted of all Norwegian residents between the years of 2000 to 2011 and aged 18 years or older. Risk was estimated from the hazard ratios constructed from Cox proportional hazards regression models adjusting for age, birth cohort, sex and education. Nine cases PLC diagnoses were detected in participants with an AHP diagnosis and AHP constituted a very high excess risk for PLC when compared to the reference population. The annual incidence rate was 0.31 for people aged 18 years or older and 0.56 for people aged 50 years or older. PLC constituted 30 per cent of all cancers diagnosed in people with an AHP diagnosis, compared to 0.5 per cent of all cancers in the reference population. Women with AHP were at an increased risk of all non-PLC malignancies compared to women from the reference population. However, no difference was found for men. Exploratory analysis suggested that people with AHP had also an increased risk of kidney and corpus uteri - cancer. No previous study has investigated incidence and risk of cancer in people with AHP at a national level or with such extensive and reliable coverage of the exposure or outcome. Our findings confirm a very high excess risk of PLC associated with AHP and supports recommendations for regular screening for PLC in people aged 50 years or older in this group. The novel findings of a moderate association between AHP and two other types of cancer extends previous findings in this area and should be investigated further in other populations.