Interferon lambda 3/4 polymorphisms are associated with AIDS-related Kaposi's sarcoma.

BACKGROUND Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections. OBJECTIVES To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS). METHODS The risk of developing Kaposi's sarcoma according to the carriage of IFNL3/4 SNPs rs8099917 and rs12980275 and their haplotypic combinations was assessed by using cumulative incidence curves and Cox regression models, accounting for relevant covariables. RESULTS Kaposi's sarcoma was diagnosed in 221 of 2558 MSM Caucasian SHCS participants. Both rs12980275 and rs8099917 were associated with an increased risk of Kaposi's sarcoma (cumulative incidence 15 versus 10%, P = 0.01 and 16 versus 10%, P = 0.009, respectively). Diplotypes predicted to produce the active P70 form (cumulative incidence 16 versus 10%, P = 0.01) but not the less active S70 (cumulative incidence 11 versus 10%, P = 0.7) form of IFNL4 were associated with an increased risk of Kaposi's sarcoma, compared with those predicted not to produce IFNL4. The associations remained significant in a multivariate Cox regression model after adjustment for age at infection, combination antiretroviral therapy, median CD4 T-cell count nadir and CD4 slopes (hazard ratio 1.42, 95% confidence interval 1.06-1.89, P = 0.02 for IFLN P70 versus no IFNL4). CONCLUSION This study reports for the first time an association between IFNL3/4 polymorphisms and susceptibility to AIDS-related Kaposi's sarcoma.