Interleukin-1β Gene (IL1B) rs1143634 (+3954 C>T) Polymorphism and Cutaneous Melanoma Risk: An Observational Case-Control Study in Northeast Italy

Background: Immune modulation is central to cutaneous melanoma, and antitumor immune responses may be influenced by host genetic background. This study investigated the association between the interleukin-1β gene (IL1B) exon 5 synonymous single-nucleotide polymorphism rs1143634 (+3954 C>T) and cutaneous melanoma in a Northeast Italian case–control cohort. Methods: The study included 133 Caucasian patients with cutaneous melanoma and 945 healthy controls from Northeast Italy. The rs1143634 polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). Results: Compared with healthy controls, melanoma patients showed higher frequencies of the rs1143634 T allele [27.8% vs. 20.3%; odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.13–2.03, p = 0.005] and CT genotype (43.6% vs. 31.6%; OR = 1.67, CI = 1.16–2.42, p = 0.006), whereas the CC genotype was less frequent (50.4% vs. 63.9%; OR = 0.57, CI = 0.40–0.83, p = 0.003). TT + CT genotypes were more frequent among non-metastatic melanoma cases than controls (OR = 2.23, CI = 1.37–3.64, p = 0.001), but the direct comparison between metastatic and non-metastatic cases was not statistically significant. Among melanoma patients, TT + CT carriers showed an inverse association with Stage IV disease (OR = 0.38, CI = 0.15–0.94, p = 0.036) and a positive association with upper-limb melanoma (OR = 9.10, CI = 1.11–75.0, p = 0.040); these subgroup findings were exploratory because of small numbers and wide confidence intervals. Conclusions: These preliminary findings suggest a possible association between IL1B rs1143634 T allele carriage and cutaneous melanoma susceptibility in this cohort. The Stage IV and upper-limb observations should be considered hypothesis-generating. Larger independent studies, correction-aware statistical designs, cytokine or expression measurements, and functional validation are needed to confirm these observations and clarify their biological relevance.