Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study

Abstract

The risk of some malignancies may be raised in patients with sickle cell disease. However, this study was based on administrative data without the scope to validate these against patients' full clinical records. Our findings need confirmation or refutation. If confirmed, work to elucidate, at the genetic and molecular level, why people with sickle cell disease have elevated risks of individual cancers might make contributions to the fundamental understanding of carcinogenesis.

Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

“…Repeated systemic administration of iron to rodents causes iron deposition with oxidative tissue injury in renal tubule epithelium, the presumed site of human RCC tumorigenesis, followed by renal tumorigenesis that mimics human ccRCC in histology, male gender predominance, and metastatic affinity for the lungs and lymph nodes [ 26 - 30 ]. In humans, increased RCC rates are reported among workers in iron/steel industries; and among patients with anemias requiring chronic transfusion, a primary cause of systemic iron overload [ 31 , 32 ]. Iron is also a prominent component of tobacco, the most well-established RCC carcinogen [ 33 ].…”

Cancer specific survival in patients with sickle cell disease

“…In our large, population-based cohort of SCD patients in California, a diagnosis of cancer is associated with worse survival, even when adjusted for SCD severity and a number of other complications previously associated with worse survival (Powars et al, 2005;Brunson et al, 2017a). The negative impact of a cancer diagnosis on survival was similar, if not stronger, than a number of other serious complications in SCD patients, an important finding given recent studies observing an increased risk of cancer in SCD patients (Seminog et al, 2016;Brunson et al, 2017b). With improvements in the treatment and care of SCD, resulting in an increased life expectancy (Platt et al, 1991;Powars et al, 2005), cancer will probably become an increasingly more frequent complication in SCD patients.…”

“…Sickle cell disease (SCD), the most common inherited blood disorder in the United States, is associated with a number of serious complications, including vaso-occlusive crisis, thrombosis, stroke, acute chest syndrome and osteonecrosis of the femoral head (Platt et al, 1991;Powars et al, 2005;Adesina et al, 2017;Brunson et al, 2017a). We and others have found an increased incidence of certain cancers among SCD patients compared to general or hospitalized populations (Seminog et al, 2016;Brunson et al, 2017b). Utilizing population-based California Cancer Registry data, we recently reported that California SCD patients have a more than twofold higher incidence of leukaemia compared to the general population of California (Brunson et al, 2017b).…”

The Disturbed Iron Phenotype of Tumor Cells and Macrophages in Renal Cell Carcinoma Influences Tumor Growth

“…The kidney plays a unique role in systemic iron homeostasis by filtering and reabsorbing iron as well as providing the main body source of erythropoietin, which promotes hemoglobin synthesis [4]. It was previously shown that renal iron overload in anemic patients requiring chronic transfusions enhanced the incidence of renal cell carcinoma (RCC) development [5]. Repeated injections of iron led to RCC development with increased metastasis to the lungs and lymph nodes in experimental models [6].…”