Effects of potentially functional polymorphisms in suppressor of cytokine signaling 3 (SOCS3) on the risk of head and neck squamous cancer
Effects of potentially functional polymorphisms in suppressor of cytokine signaling 3 (SOCS3) on the risk of head and neck squamous cancer
复制标题
细胞因子信号传导抑制因子 3 (SOCS3) 的潜在功能多态性对头颈鳞状癌风险的影响。
DOI：
10.1111/jop.12539
复制
发表时间：
2017-09-01
影响因子：
3.3
通讯作者：
Ma, Hongxia
中科院分区：
文献类型：
--
作者：
Hang, Dong;Yin, Yin;Ma, Hongxia
细胞因子信号转导抑制因子3(SOCS3)是JAK/STAT信号通路的抑制因子，在肿瘤发生中起重要作用。SOCS3和JAK2基因多态性可能影响基因的表达或功能，从而影响疾病的易感性，但在头颈部鳞状细胞癌中这种作用尚未被评估。方法采用病例对照研究方法，对576例头颈部鳞状细胞癌患者和1552例来自中国的非肿瘤对照进行病例对照研究。使用Infinium BeadChip平台对生物信息学工具预测的7个潜在功能多态进行了基因分型。结果发现，位于SOCS33非翻译区的rs2280148与HNSCC的发病风险显著相关(加性模型：调整后OR=1.21，95%CI=1.03~1.43，P=0.021)。此外，位于SOCS3启动子区域的rs8064821与癌症风险降低有关(加性模型：校正OR=0.83，95%CI=0.71~0.97，P=0.022)。根据风险等位基因的数量对这些变异进行联合分析，发现SOCS3基因多态性对人类非小细胞肺癌的风险有显著的座位剂量效应(P-趋势=0.006)。结论首次提供了SOCS3基因多态可能影响人类非小细胞肺癌风险的证据，可作为识别疾病高危个体的新的生物标志物。
BackgroundSuppressor 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).MethodsA 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.ResultsWe 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 (P-trend = 0.006).ConclusionsWe 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.