Relation of IL-18 Polymorphism to the Susceptibility and Clinical Feature of Multiple Myeloma in Japanese Patients

Multiple myeloma (MM) is characterized as a malignant plasma cell proliferation. The growth of MM plasma cells is dependent on a complex interplay among various cytokines, adhesion molecules and other factors in the tumor microenvironment. Dysregulation of several cytokines have been detected in some patients with MM, and were known to be associated with an adverse prognosis. Interleukin-18 (IL-18) plays a role in the host's response to tumors and angiogenesis. Several mouse model experiments have shown that IL-18 may have anti-tumor effect in multiple myeloma (MM). The polymorphisms of IL-18 gene have been implicated in several cancers; however, it is unclear whether IL-18 polymorphisms alter the susceptibility and clinical outcome of MM. We examined −137(G/C) polymorphisms and −607(C/A) of IL-18 genes in Japanese patients with MM.

Ninety three patients with MM [age range, 35–83 years; stage I (n=8), stage II (n=23), stage III (n=62); IgA (n=15), IgG (n=55), IgD (n=2), non-secretory (n=3), Bence Jones (n=18)], and 153 healthy controls were included. MM was diagnosed on International Myeloma Working Group Criteria. The staging for MM is defined by Durie and Salmon staging system or International Staging System (ISS). Genotyping was determined by the allelic specific polymerase chain reaction technique. Genotype, allele, and haplotype frequencies were compared between the study groups using χ²-test. The characteristics and laboratory features of the MM patients with each IL-18 polymorphism were compared using χ²-tests and student t-tests. Probability values <0.05 were considered statistically significant. Allpatients and healthy controls were provided written information about the study.

Patients with MM had a significantly higher frequency of the IL-18-137 CC or GC genotype compared to the control group (34% vs. 22%, P<0.05). The number of IL-18-137 C alleles among the patients with MM was also higher than in the control group (19% vs. 12%, p<0.05). Patients with MM patients had significantly more −607A/−137C haplotype (18.8% vs. 10.9%, p=0.02) than control group. Furthermore, IL-18-137 CC or GC genotype was significantly associated with advanced international staging system (ISS) (P<0.05) and lower hemoglobin level (8.8±2.6 mg/dL vs. 9.9±2.4 mg/dL, p=0.04). In contrast to IL-18-137(G/C), no significant differences in the genotype or allele frequencies of IL-18-607(C/A) were observed between MM patients and the control group. In the clinical characteristics at diagnosis including sex, Ig type, and ISS, there was also no difference between patients with IL-18-607 GG genotype and non IL-18-607 GG genotype.

These results suggest that the IL-18-137(G/C) may be associated with the susceptibility and the clinical feature of MM in Japanese patients.

No relevant conflicts of interest to declare.