Cancer risk in persons with new-onset anaemia: a population-based cohort study in Denmark

Abstract

Background: The time interval from first symptom and sign until a cancer diagnosis significantly affects the prognosis. Therefore, recognising and acting on signs of cancer, such as anaemia, is essential. Evidence is sparse on the overall risk of cancer and the risk of specific cancer types in persons with new-onset anaemia detected in an unselected general practice population. We aimed to assess the risk of cancer in persons with new-onset anaemia detected in general practice, both overall and for selected cancer types.

Methods: This observational population-based cohort study used individually linked electronic data from laboratory information systems and nationwide healthcare registries in Denmark. We included persons aged 40-90 years without a prior history of cancer and with new-onset anaemia (no anaemia during the previous 15 months) detected in general practice in 2014-2018. We measured the incidence proportion and standardised incidence ratios of a new cancer diagnosis (all cancers except for non-melanoma skin cancers) during 12 months follow-up.

Results: A total of 48,925 persons (median [interquartile interval] age, 69 [55-78] years; 55.5% men) were included in the study. In total, 7.9% (95% confidence interval (CI): 7.6 to 8.2) of men and 5.2% (CI: 4.9 to 5.5) of women were diagnosed with cancer during 12 months. Across selected anaemia types, the highest cancer incidence proportion was seen in women with 'anaemia of inflammation' (15.3%, CI: 13.1 to 17.5) (ferritin > 100 ng/mL and increased C-reactive protein (CRP)) and in men with 'combined inflammatory iron deficiency anaemia' (19.3%, CI: 14.5 to 24.1) (ferritin < 100 ng/mL and increased CRP). For these two anaemia types, the cancer incidence across cancer types was 10- to 30-fold higher compared to the general population.

Conclusions: Persons with new-onset anaemia detected in general practice have a high cancer risk; and markedly high for 'combined inflammatory iron deficiency anaemia' and 'anaemia of inflammation'. Anaemia is a sign of cancer that calls for increased awareness and action. There is a need for research on how to improve the initial pathway for new-onset anaemia in general practice.

Keywords: Anemia; Cancer risk; Cohort studies; Denmark; General practice.

Fig. 1

Sources of data linked at the individual level

Fig. 2

Flowchart of the study population

Fig. 3

a Cumulative cancer incidence in men with new-onset anaemia during 12-month (by anaemia types). Abbreviations: AI: anaemia of inflammation, CIIDA: combined inflammatory iron deficiency anaemia, IDA: iron deficiency anaemia, Unclassified anaemia: the anaemia is not classifiable according to a guideline. For overall cancer risk: all cancers were included, except for non-melanoma skin cancer. Proportions with < 5 events are not shown to protect confidentiality.3b. Cumulative cancer incidence in women with new-onset anaemia during 12-month (by anaemia types). Abbreviations: AI: anaemia of inflammation, CIIDA: combined inflammatory iron deficiency anaemia, IDA: iron deficiency anaemia, Unclassified anaemia: the anaemia is not classifiable according to a guideline. For overall cancer risk: all cancers were included, except for non-melanoma skin cancer. Proportions with < 5 events are not shown to protect confidentiality.

Fig. 4

Standardized incidence ratios^a for cancer^b in persons with new-onset anaemia (by anaemia types). Abbreviations: AI: anaemia of inflammation, CI: 95% confidence interval, CIIDA: combined inflammatory iron deficiency anaemia, IDA: iron deficiency anaemia, SIR: Standardized incidence ratios, Unclassified: the anaemia is not classifiable according to a guideline. SIRs with < 5 events are not shown to protect confidentiality. Error bars = 95% CI (some error bars are not seen because of a narrow 95% CI). ^aBased on age- and sex-specific cancer incidence rates in the general Danish population (from the NORDCAN database). ^bNon-melanoma skin cancer excluded

Fig. 5

Associations of patient characteristics and cancer in persons with new-onset anaemia. Abbreviations: CI: 95% confidence interval, HR: hazard ratio, No: number. Error bars = 95% CI (some error bars are not seen because of a narrow 95% CI). Hazard ratios are displayed on a log scale. ^aAdjusted for age (continuous), anaemia severity, civil status, educational level, income, comorbidity, and sex. ^bNon-melanoma skin cancer excluded. ^cAnaemia severity was defined according to WHO’s guidelines: mild anaemia (haemoglobin > 110 g/L), moderate anaemia (haemoglobin 80–110 g/L), and severe anaemia (haemoglobin < 80 g/L). ^dComorbidity was registered ten years prior to the index date and categorized according to the chronic disease groups (CDGs)