title: CTLA-4 gene and susceptibility to human papillomavirus-16-associated cervical squamous cell carcinoma in Taiwanese women.
abstract: Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer. The host immunogenetic background plays an important role in the persistence of HPV infection and subsequent development of cervical cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed mainly on activated T cells and is important in the down-regulation of T-cell activation. The aim of this study was to determine if polymorphisms of the CTLA-4 gene are associated with HPV-induced cervical cancer in Taiwanese women. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype -318 C/T, +49 A/G and CT60 A/G polymorphisms in 144 women with cervical squamous cell carcinoma (CSCC) and 378 ethnicity-matched healthy control women. The presence and genotypes of HPV in CSCC were determined by E6-, E7-based nested polymerase chain reaction. The frequency of C/T genotype of -318 C/T polymorphism was significantly higher in patients with HPV-16-positive CSCC compared with controls (odds ratio = 1.99, 95% confidence interval = 1.16-3.42, P(c) = 0.03). No significant associations were found for +49 A/G and CT60 A/G polymorphisms. Analysis of haplotypes, computationally inferred from genotype data, also revealed no significant differences in distribution among all subjects with CSCC, those with HPV-16-positive CSCC and controls. Our results suggest that the -318 C/T variant in the promoter region of the CTLA-4 gene is associated with HPV-16-associated CSCC in Taiwanese women.
authors.affiliation: Department of Gynecology and Obstetrics, Mackay Memorial Hospital, Tamshui, Taipei, Taiwan.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Su
authors.forename: Tzu-Yang
authors.initials: TY
authors.lastname: Chang
authors.forename: Yann-Jinn
authors.initials: YJ
authors.lastname: Lee
authors.forename: Chih-Kai
authors.initials: CK
authors.lastname: Chen
authors.forename: Hsin-Fu
authors.initials: HF
authors.lastname: Liu
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Chu
authors.forename: Marie
authors.initials: M
authors.lastname: Lin
authors.forename: Pu-Tsui
authors.initials: PT
authors.lastname: Wang
authors.forename: Wen-Chu
authors.initials: WC
authors.lastname: Huang
authors.forename: Tze-Chien
authors.initials: TC
authors.lastname: Chen
authors.forename: Yuh-Cheng
authors.initials: YC
authors.lastname: Yang
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D000943:Antigens, Differentiation / Q000235:genetics* / Q000502:physiology; D060908:CTLA-4 Antigen; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D030361:Papillomavirus Infections / Q000209:etiology* / Q000235:genetics; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013624:Taiwan; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human