title: A novel mechanism of rs763110 polymorphism contributing to cervical cancer risk by affecting the binding affinity of C/EBPβ and OCT1 complex to chromatin.
abstract: Recently, several studies have showed that FAS (rs2234767, rs1800682) and FASL (rs763110) functional single nucleotide polymorphisms (SNPs) were associated with the risk of various cancers. However, the association between cervical cancer risk and the three SNPs above remained inconclusive. In this work, we performed a two-stage case-control study on 1155 cervical cancer patients and 1252 matched healthy controls to determine the roles of the mentioned SNPs in cervical cancer susceptibility. We genotyped the FAS rs2234767, rs1800682, and FASL rs763110 polymorphisms using PCR-TaqMan assays. Results revealed that the rs763110 TT genotype significantly increased the risk of cervical cancer compared with the CC/CT genotype (adjusted OR = 1.70, 95% CI = 1.19-2.42). However, we did not observe any association between the cervical cancer risk and the rs2234767 and rs1800682 polymorphisms. The immunohistochemistry assay showed that patients carrying the rs763110 TT genotype presented a lower cancerous FASL expression than that of the CC/CT genotypes. Chromatin immunoprecipitation (ChIP) and Sequential Chromatin immunoprecipitation assays also demonstrated that OCT1 was recruited to the FASL promoter region and regulated the FASL gene transcription by interacting with C/EBPβ. In conclusion, this study provided evidence indicating that the rs763110 variant in the FASL promoter was associated with the risk of cervical cancer by affecting the binding affinity of the C/EBPβ/OCT1 complex to chromatin.
authors: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, China.|Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Shenshen
authors: S
authors: Wu
authors: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Shizhi
authors: S
authors: Wang
authors: School of Continuing Education, Nanjing Medical University, Nanjing, China.
authors: You
authors: Y
authors: Fu
authors: Medical Oncology, Jiangsu Cancer Hospital, Nanjing, China.
authors: Weiyan
authors: W
authors: Tang
authors: Core Laboratory, Nantong Tumor Hospital, Nantong, China.
authors: Hua
authors: H
authors: Jin
authors: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Qingtao
authors: Q
authors: Meng
authors: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Chengcheng
authors: C
authors: Zhang
authors: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Mengjing
authors: M
authors: Cui
authors: Clinical Lab, Nantong Tumor Hospital, Nantong, China.
authors: Xiaoli
authors: X
authors: Cao
authors: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Xiaobo
authors: X
authors: Li
authors: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
authors: Zhengdong
authors: Z
authors: Zhang
authors: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, China.|Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
authors: Rui
authors: R
authors: Chen
mesh_terms: D000028:Abortion, Induced / Q000706:statistics & numerical data; D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D047369:Chromatin Immunoprecipitation; D053222:Fas Ligand Protein / Q000235:genetics* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D027702:Organic Cation Transporter 1 / Q000378:metabolism*; D010298:Parity; D020641:Polymorphism, Single Nucleotide; D034741:RNA, Small Interfering / Q000235:genetics; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics*; D019014:fas Receptor / Q000502:physiology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D009363:Neoplasm Proteins; D027702:Organic Cation Transporter 1; D034741:RNA, Small Interfering; D019014:fas Receptor
keywords: FASL; cervical cancer; mechanism; polymorphism; risk