Spectrum of Immune-Related Conditions Associated with Risk of Keratinocyte Cancers among Elderly Adults in the United States

Abstract

Elevated keratinocyte carcinoma (KC) risk is present with several immune-related conditions, e.g., solid organ transplantation and non-Hodgkin lymphoma. Because many immune-related conditions are rare, their relationships with KC have not been studied. We used Medicare claims to identify cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) cases in 2012, and controls matched on sex and age. All subjects were aged 65–95 years, of white race, and had attended ≥1 dermatologist visit in 2010–2011. Immune-related conditions were identified during 1999–2011 using Medicare claims. Associations were estimated with logistic regression, with statistical significance determined after Bonferroni correction for multiple comparisons. We included 258,683 SCC and 304,903 BCC cases. Of 47 immune-related conditions, 21 and 9 were associated with increased SCC and BCC risk, respectively. We identified strongly elevated KC risk with solid organ transplantation (SCC odds ratio [OR]=5.35; BCC OR=1.94) and non-Hodgkin lymphoma (SCC OR=1.62; BCC OR=1.25). We identified associations with common conditions, e.g., rheumatoid arthritis (SCC OR=1.06, 95% confidence interval [95%CI]=1.04–1.09) and Crohn’s disease (SCC OR=1.33, 95%CI=1.27–1.39; BCC OR=1.10, 95%CI=1.05–1.15), and rare or poorly characterized conditions, e.g., granulomatosis with polyangiitis (SCC OR=1.88, 95%CI=1.61–2.19), autoimmune hepatitis (SCC OR=1.81, 95%CI=1.52–2.16), and deficiency of humoral immunity (SCC OR=1.51, 95%CI=1.41–1.61; BCC OR=1.22, 95%CI=1.14–1.31). Most conditions were more positively associated with SCC than BCC. Associations were generally consistent regardless of prior KC history. Many immune-related conditions are associated with elevated KC risk, and appear more tightly linked to SCC. Immunosuppression or immunosuppressive treatment may increase KC risk, particularly SCC.

Keratinocyte Carcinomas: Current Concepts and Future Research Priorities

“…While certain primary immunodeficiencies predispose to keratinocyte carcinoma (ref. 29; e.g., severe combined immunodeficiency, Wiskott-Aldrich syndrome, and dyskeratosis congenita), keratinocyte carcinomas are more common in acquired immunodefi-ciency, including immunosuppressive drug therapy (e.g., in solidorgan transplantation), immunemediated/autoimmune inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), vasculitis and rheumatoid arthritis (RA), nonHodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL), and HIV infection (30).…”

Risk of Kaposi sarcoma after solid organ transplantation in the United States

“…Recently, increased risk of KS has been associated with higher ambient ultraviolet radiation (UVR) and history of cutaneous basal or squamous cell carcinoma (referred to collectively as “keratinocyte carcinomas”) among HIV‐infected men . Transplant recipients have a very high risk of keratinocyte carcinoma, but the association of ambient UVR or non‐KS skin cancers with KS risk has not been assessed among transplant recipients. While use of immunosuppressive medications is associated with increased risk of KS, to our knowledge, prospective data on specific immunosuppressive medications and trends in KS risk are limited.…”

Epidemiologic perspectives on immunosuppressed populations and the immunosurveillance and immunocontainment of cancer

“…For example, patients with autoimmune conditions, who are often treated with immunomodulating medications, have elevated risk for DLBCL 50. Patients with NHL or chronic lymphocytic leukemia have elevated incidence of cutaneous SCC and MCC [51][52][53].…”