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.