KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population

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• 作者：Dong Hang ; Hua Yuan ; Li Liu ; Lihua Wang ; Limin Miao ; Meng Zhu ; Jiangbo Du ; Juncheng Dai ; Zhibin Hu ; Ning Chen ; Hongbing Shen and Hongxia Ma
• 刊名：Molecular Carcinogenesis
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：56
• 期：1
• 页码：232-237
• 全文大小：99K
• ISSN：1098-2744

文摘

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 (P_trend = 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.