Effects of potentially functional polymorphisms in suppressor of cytokine signaling 3 (SOCS3) on the risk of head and neck squamous cancer.

BACKGROUND: Suppressor of cytokine signaling 3 (SOCS3) has been identified as an inhibitor of JAK/STAT pathway that plays a significant role in carcinogenesis. SOCS3 and JAK2 polymorphisms may influence the gene expression or function, contributing to the disease susceptibility; however, such effect has not been evaluated in head and neck squamous cell carcinoma (HNSCC).

METHODS: A case-control study was performed to test the associations of SOCS3 and JAK2 polymorphisms with risk of HNSCC in 576 cases and 1552 cancer-free controls from China. Seven potentially functional polymorphisms predicted by bioinformatics tools were genotyped using Infinium BeadChip platform. The association between genotypes and HNSCC risk was estimated by computing odds ratios (ORs) and 95% confidence intervals (CIs) in univariate and multivariate logistic regression models.

RESULTS: We found that rs2280148 located at 3'-untranslated region of SOCS3 was significantly associated with an increased risk of HNSCC (additive model: adjusted OR = 1.21, 95% CI = 1.03-1.43, P = 0.021). Moreover, rs8064821 located in the promoter region of SOCS3 was linked with a decreased risk of the cancer (additive model: adjusted OR = 0.83, 95% CI = 0.71-0.97, P = 0.022). Combined analysis of these variants by the number of risk alleles showed a significant locus-dosage effect on the risk of HNSCC (Ptrend = 0.006).

CONCLUSIONS: We provided the first evidence that SOCS3 polymorphisms may influence the risk of HNSCC, which could be applied as novel biomarkers to identify individuals at high risk of the disease.