CTLA-4 and TNFRSF1B genetic variants in clinicopathological aspects and outcome of cutaneous melanoma.

Abstract

Cutaneous melanoma is the most aggressive form of skin cancer, influenced by environmental and genetic factors, particularly immune-related genes like cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) and TNFRSF1B . We investigated the association of inherited single nucleotide variants in CTLA-4 (rs11571316, rs62182595, rs11571315, and rs4553808) and TNFRSF1B (rs3397, rs1061622, rs1061624, and rs1061628) with clinicopathological aspects and survival of 428 cutaneous melanoma patients. Carriers of CTLA-4 rs4553808 AG/GG plus TNFRSF1B rs3397 TC/CC genotypes were younger at diagnosis. The CTLA-4 rs4553808 AA plus TNFRSF1B rs1061624 GG genotypes were more common in male than female patients. CTLA-4 rs4553808 AA or rs62182595 GG plus TNFRSF1B rs1061624 GG were more frequent among patients with tumors on the head, neck, and trunk. Patients older than 54 years with CTLA-4 rs11571316 GG and TNFRSF1B rs3397 TT had a 3.04-times greater chance of progression to death because of tumor effects. Patients with head, neck, and trunk cutaneous melanoma carrying CTLA-4 rs4553808 AG/GG and TNFRSF1B rs1061624 GA/AA had a 2.30-times greater chance of recurrence, progression, or tumor-related death. Patients with head, neck, and trunk cutaneous melanoma carrying CTLA-4 rs4553808 AG/GG and TNFRSF1B rs1061624 GA/AA, and CTLA-4 rs62182595 GA/AA and TNFRSF1B rs1061624 GA/AA genotypes had a 2.97- and 2.75-times greater chance of progression to death because of tumor effects, respectively. These findings suggest immune modulation linked to these single nucleotide variants may facilitate cutaneous melanoma progression and highlight the potential for immunotherapeutic strategies in genetically predisposed patients.