"Sickle cell trait and the risk for malignancy".

[INTRODUCTION] Sickle cell trait (SCT) is a hereditary condition that affects millions worldwide, predominantly in individuals of African, Mediterranean, and Middle Eastern descent. While traditionally considered a benign carrier state, emerging evidence suggests a potential association between SCT and malignancies. This study aims to evaluate the relationship between SCT and the risk of multiple myeloma, renal cancer, leukemia, hepatocellular carcinoma (HCC), and colorectal cancer.

[METHODS] This study utilized de-identified electronic health records from the TriNetX database, covering a 20-year period. A retrospective cohort analysis was conducted to assess cancer incidence and survival outcomes among SCT and sickle cell disease (SCD) patients. Statistical analyses included risk difference (RD), risk ratio (RR), odds ratio (OR), Kaplan-Meier survival curves, and hazard ratios (HR) to determine associations between SCT and cancer risk.

[RESULTS] SCT was not associated with an increased risk for most cancers. However, individuals with SCT had a significantly lower risk of leukemia compared to those with SCD (RR =0.464, OR = 0.463, p < 0.001), suggesting a potential protective effect. Conversely, a modest but statistically insignificant increase in renal cancer risk was observed in SCT individuals (RR = 1.201, OR = 1.202, p = 0.059). No significant associations were found between SCT and multiple myeloma, HCC, or colorectal cancer.

[DISCUSSION] These findings highlight a complex relationship between SCT and malignancy risk. The observed protective effect against leukemia suggests a potential hematopoietic or immune-mediated mechanism. Meanwhile, the slight increase in renal cancer risk may be linked to chronic kidney stress and hematuria. Further studies are needed to validate these associations and investigate underlying biological mechanisms.

[CONCLUSION] SCT does not significantly increase cancer risk overall but may confer protection against leukemia while showing a potential, though inconclusive, link to renal cancer. These findings emphasize the need for continued surveillance and further epidemiological studies to refine cancer risk assessment in SCT populations.