KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population
KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population
复制标题
KIT多态性与中国人群头颈鳞癌风险相关
DOI：
10.1002/mc.22487
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发表时间：
2017-01-01
影响因子：
4.6
通讯作者：
Ma, Hongxia
中科院分区：
文献类型：
--
作者：
Hang, Dong;Yuan, Hua;Ma, Hongxia
KITLG/KIT通路在包括头颈部鳞状细胞癌（HNSCC）在内的多种人类癌症中起着至关重要的作用。KITLG和KIT的遗传变异可能影响这些基因的表达或功能，从而改变癌症风险。在这项研究中，我们评估了中国人群中KITLG和KIT多态性与HNSCC风险的关系。在576例HNSCC患者和1552例健康对照的病例对照研究中，对KITLG和KIT基因中的22个标记snp进行了基因分型。Logistic回归分析显示，KIT上游SNP rs6554198[加性模型：校正优势比(OR) = 0.85, 95%置信区间(CI) = 0.74-0.97, P = 0.019]和两个内含子SNP rs2237025（加性模型：校正OR = 0.82, 95%CI = 0.70-0.95, P = 0.007）和rs17084687（加性模型：校正OR = 0.85, 95%CI = 0.73-0.99, P = 0.042）与HNSCC风险降低显著相关。三个snp的联合分析显示，携带保护性等位基因的受试者患HNSCC的风险呈剂量-反应方式降低（p趋势= 0.001）。此外，交互作用分析显示rs17084687与饮酒对HNSCC风险存在显著的乘法交互作用（P = 0.012）。荧光素酶活性测定显示，潜在功能rs6554198等位基因A导致KIT转录活性明显低于风险等位基因g。综上所述，我们的研究结果提示KIT基因snp可能在HNSCC遗传易感性中起作用，这可能有助于我们对该病发病机制的理解。©2016 Wiley期刊公司
KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorphisms with HNSCC risk among Chinese population. Twenty‐two tagging SNPs in KITLG and KIT genes were genotyped in a case‐control study with 576 HNSCC patients and 1552 healthy controls. Logistic regression analyses revealed that an upstream SNP rs6554198 [additive model: adjusted odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.74–0.97, P = 0.019] and two intron SNPs rs2237025 (additive model: adjusted OR = 0.82, 95%CI = 0.70–0.95, P = 0.007), and rs17084687 (additive model: adjusted OR = 0.85, 95%CI = 0.73–0.99, P = 0.042) of KIT were significantly associated with the decreased risk of HNSCC. Combined analysis of the three SNPs showed that subjects carrying the protective alleles had decreased risk of HNSCC in a dose‐response manner (Ptrend = 0.001). Furthermore, interaction analyses revealed a significant multiplicative interaction between rs17084687 and drinking on HNSCC risk (P = 0.012). Luciferase activity assay indicated that the allele A of potentially functional rs6554198 led to significantly lower transcription activity of KIT compared to the risk allele G. Summarily, our findings suggested that SNPs in KIT gene may play a role in genetic susceptibility to HNSCC, which may improve our understanding of the pathogenic mechanisms of this disease. © 2016 Wiley Periodicals, Inc.