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

Abstract

Background: Elevated keratinocyte carcinoma 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 keratinocyte carcinoma have not been studied.Methods: 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 to 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.Results: 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 keratinocyte carcinoma risk with solid organ transplantation (SCC 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 keratinocyte carcinoma history.Conclusions: Many immune-related conditions are associated with elevated keratinocyte carcinoma risk and appear more tightly linked to SCC.Impact: Immunosuppression or immunosuppressive treatment may increase keratinocyte carcinoma risk, particularly SCC. Cancer Epidemiol Biomarkers Prev; 26(7); 998-1007. ©2017 AACR.

Figure 1

Associations of immune-related conditions and controls conditions with squamous cell carcinoma of the skin Each point represents the association between a condition and squamous cell carcinoma risk among subjects with at least 1 dermatology visit, adjusted for age, sex, dermatologist visits, non-dermatologist physician visits, and ultraviolet B exposure based on residence. The dotted horizontal line represents p=0.000439, the Bonferroni threshold for statistical significance. As the y-axis shows p-values plotted on the -log₁₀ scale, associations appearing above the dotted line are statistically significant.

Figure 2

Associations of immune-related conditions and controls conditions with basal cell carcinoma of the skin Each point represents the association between a condition and basal cell carcinoma risk among subjects with at least 1 dermatology visit, adjusted for age, sex, dermatologist visits, non-dermatologist physician visits, and ultraviolet B exposure based on residence. The dotted horizontal line represents p=0.000439, the Bonferroni threshold for statistical significance. As the y-axis is plotted on the -log₁₀ scale, associations appearing above this dotted line are statistically significant.

Figure 3

Comparison of odds ratios for associations of immune-related conditions with squamous cell carcinoma and basal cell carcinoma Each point represents a condition and its associations with SCC and BCC risk based on models for people with at least one dermatology visit in 2010–2011, adjusted for age, sex, dermatologist visits, non-dermatologist physician visits, and ultraviolet B exposure based on residence. Odds ratios are depicted on logarithmic scales. The solid diagonal line represents where conditions would be if associations with SCC and BCC were equal. Conditions above and to the left of the solid line have a more positive association with SCC than BCC. Conditions below and to the right of the solid line have a more positive relationship with BCC than SCC. SCC=squamous cell carcinoma of the skin, BCC=basal cell carcinoma of the skin