Incidence of cancer (other than gastric cancer) in pernicious anaemia: A systematic review with meta-analysis

Background: Pernicious anaemia (PA) is associated with increased gastric cancer risk, but the evidence is conflicting regarding the associated risk of other cancers. Aim: To systematically determine the incidence rates of gastro-intestinal cancers other than gastric cancers (GI-other-than-GC) and non-gastrointestinal cancers (non-GIC) in PA adults, globally and per tumour site, and the risk associated with PA for GI-other than GC and non-GIC. Methods: Studies of PA patients reporting the incidence of GI-other-than-GCs and non-GICs were identified with MEDLINE (PubMed)-EMBASE (from first date available to April 2017). A meta-analysis of annual cancer incidence rates was performed. The outcome was the cumulative incidence of GI-other-than-GCs and non-GICs (ratio between the numbers of new cancer cases identified during the follow-up period and the number of PA patients) and the incidence rate expressed as the rate of events-per-time-unit (person-years). Results: Of 82,257 PA patients, the pooled incidence rates/100 person-years for non-GCs and non-GICs of 0.27 (95% CI: 0.16-0.42) and 0.23 (95% CI: 0.22-0.25) were calculated by meta-analysis. Compared to the GLOBOCAN data for the general population from the countries of the included studies, the meta-analysis showed an overall relative risk (RR) of cancer in PA of 0.68 (95% CI: 0.48-0.95). PA patients had a lower RR of colorectal, breast, liver, oesophageal, lung, thyroid, ovary, non-melanoma skin and kidney cancers but had a higher RR of biliary tract cancer (1.81: 1.21-2.70), multiple myeloma (2.83: 1.76-4.55), Hodgkin's lymphoma (3.0: 1.35-6.68), non-Hodgkin's lymphoma (2.08: 1.58-2.75), and leukaemia (1.56: 1.16-2.12). Conclusion: An overall lower RR of cancers-other-than-gastric-cancer in PA patients but an increased RR of biliary tract cancers and haematological malignancies was observed. (c) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.