Associations between polymorphisms in IL-12A, IL-12B, IL-12Rβ1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer

The aim of this study was to investigate whether IL-12A, IL-12B, IL-12R beta 1, and IL-27 gene polymorphisms and serum levels of IL-12, IL-27 are associated with esophageal cancer. We genotyped IL-12A gene rs568408, IL-12B gene rs3212227, IL-12R beta 1 gene 378 C/G, IL-27 gene rs153109, rs17855750, and rs181206 polymorphisms in a case-control study of 426 esophageal cancer patients and 432 health controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay. Both serum IL-12p40 and IL-27p28 levels were significantly higher in controls than those in patients (P < 0.01). Rs568408 AG/AA, rs3212227 CC/AC, and IL-12R beta 1 378 GG/GC genotypes were associated with significantly increased risk of esophageal cancer (rs568408: chi(2) = 5.704, P = 0.017; rs3212227: chi(2) = 7.689, P = 0.006; IL-12R beta 1 378C/G: chi(2) = 5.206, P = 0.023). Moreover, rs3212227 CC/AC and 378 GG/GC genotypes were observed significantly associated with decreased serum IL-12p40 level in patients compare to other genotypes (rs3212227: t = 2.129, P = 0.034; IL-12R beta 1 378 C/G: t = 2.178, P = 0.030). Furthermore, frequency of rs3212227 CC/AC genotypes was significantly higher in patients with poor differentiation than those with AA genotype (chi(2) = 4.314, P = 0.035). Our data suggest that the impaired production of IL-12p40 and IL-27p28 behaves as risk factors for esophageal cancer occurrence. IL-12B gene rs3212227 CC/AC and IL-12R beta 1 gene 378 GG/GC genotypes, which associated with decreased IL-12p40 level, may contribute to esophageal cancer susceptibility.