Interleukin-1β Gene (IL-1B) rs16944 (-511 C > T) Promoter Polymorphism Is Associated with Cutaneous Melanoma...

Immunity plays critical roles in cutaneous melanoma. We investigated the association between the pro-inflammatory interleukin-1β gene (IL-1B) rs16944 (-511 C > T) promoter single nucleotide polymorphism (SNP) and cutaneous melanoma susceptibility and clinical features. This observational case-control study included 133 patients with cutaneous melanoma and 900 healthy controls from Northeastern Italy. The rs16944 C > T polymorphism was determined by genomic DNA restriction fragment analysis. The IL-1B rs16944 C allele (OR = 1.44, p = 0.014) and CC genotype (OR = 1.48, p = 0.037) were associated with modestly higher odds of melanoma. Among melanoma patients, the CC genotype was associated with Stage I disease (OR = 2.45, p = 0.016) and Breslow thickness ≤ 0.75 mm (OR = 2.27, p = 0.049), whereas it was less frequent in Stage IV melanoma (OR = 0.37, p = 0.029). The CT genotype was associated with Stage IV melanoma (OR = 3.03, p = 0.014) and with lower-limb (OR = 2.45, p = 0.038) and lower-extremity (OR = 3.09, p = 0.005) melanoma. These divergent associations are exploratory and do not establish disease trajectory or a functional effect of rs16944; mechanistic interpretation remains uncertain because IL-1β expression or activity was not measured in this cohort. To our knowledge, this is the first report of an association between a genetic polymorphism and lower-limb/lower-extremity melanoma. These exploratory findings require confirmation in independent cohorts.