Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma

Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1β. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish case-control study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.27-3.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.33-6.30), which intensified in male patients (OR 4.03, CI 1.40-11.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.04-3.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.33-25). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations.