title: KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
mesh_terms: D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D019089:Stem Cell Factor / Q000235:genetics
chemical_list: D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
keywords: KIT gene; head and neck squamous cell carcinoma; single nucleotide polymorphism