Risk of cancer in patients with thalassemia and sickle cell disease: a systematic review

Individuals with thalassemia or sickle cell disease (SCD) are at an elevated risk of developing cancer, yet the full extent of this risk remains inadequately characterised.

We conducted a systematic review using three databases (MEDLINE, EMBASE and Scopus) to compare the cancer risk in patients with thalassemia and SCD with that of the general population. Secondly, we assessed the impact of other putative risk factors in patients with thalassemia and SCD on cancer risk.

Five studies from four countries were included, encompassing a total of 24,439 individuals overall. The risk estimates of developing cancer were highly variable, being affected by study design, population and comparators recruited, and type of cancer. The results showed an elevated cancer risk in SCD and thalassemia patient groups, with the highest incidence observed for hematologic malignancies (especially myeloid leukaemia in SCD patients). Patients with transfusion-dependent thalassemia had a significantly higher overall cancer risk, particularly hepatocellular carcinoma, compared to both non-transfusion-dependent patients and the general population. Other key factors seem to contribute to the increased cancer risk besides transfusion dependency, viral infections, and use of iron chelators. However, people with hemoglobinopathies appeared to be at lower risk of breast and prostate cancer compared to the general population.

The findings are limited by variability among studies, including differences in control groups, inconsistent reporting of outcomes, and missing assessments of confounding factors. Therefore, future research with robust methods is essential to improve cancer surveillance and develop targeted prevention strategies for high-risk populations.