CTLA-4 gene and susceptibility to human papillomavirus-16-associated cervical squamous cell carcinoma in Taiwanese women.
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.
Su
Tsung-Hsien
TH
Department of Gynecology and Obstetrics, Mackay Memorial Hospital, Tamshui, Taipei, Taiwan.
Chang
Tzu-Yang
TY
Lee
Yann-Jinn
YJ
Chen
Chih-Kai
CK
Liu
Hsin-Fu
HF
Chu
Chen-Chung
CC
Lin
Marie
M
Wang
Pu-Tsui
PT
Huang
Wen-Chu
WC
Chen
Tze-Chien
TC
Yang
Yuh-Cheng
YC
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
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human