Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception

Objectives: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.

Design and methods: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.

Results: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p = 0.032, Mann–Whitney test) and presented a trend for lower levels of pain (p = 0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR = 4.074, p = 0.010, Pearson χ2 test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p = 0.053, Pearson χ2 test).

Conclusions: Our results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.