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Carcinogenesis Advance Access first published online on March 6, 2007
This version published online on March 10, 2007
Carcinogenesis, doi:10.1093/carcin/bgm043
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

CTLA-4 gene and susceptibility to human papillomavirus 16-associated cervical squamous cell carcinoma in Taiwanese women

Tsung-Hsien Su1,4,§, Tzu-Yang Chang2,§, Yann-Jinn Lee2,3,6, Chih-Kai Chen2, Hsin-Fu Liu2, Chen-Chung Chu2, Marie Lin2, Pu-Tsui Wang1, Wen-Chu Huang1, Tze-Chien Chen1 and Yuh-Cheng Yang1,2,4,5

1 Department of Gynecology and Obstetrics, Mackay Memorial Hospital, Taipei
2 Department of Medical Research, Mackay Memorial Hospital, Taipei
3 Department of Pediatrics, Mackay Memorial Hospital, Taipei
4 Department of Mackay Medicine, Nursing and Management College, Taipei
5 Department of Gynecology and Obstetrics, Taipei Medical University, Taipei, Taiwan
6 Department of Pediatrics, Taipei Medical University, Taipei, Taiwan

Address correspondence and reprint requests to Yuh-Cheng Yang, MD, Departments of Gynecology and Obstetrics, and Medical Research, Mackay Memorial Hospital, 45, Min-Sheng Rd., Tamshui 25115, Taipei County, Taiwan. Tel: 886-2-28094661 ext. 3049, Fax: 886-2-28094679. E-Mail: eugene{at}ms2.mmh.org.tw

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 (PCR-RFLP) 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 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined by E6, E7-based nested PCR. The frequency of C/T genotype of –318 C/T polymorphism was significantly higher in patients with HPV-16 positive CSCC compared with controls (OR = 1.99, 95% CI = 1.16-3.42, Pc = 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.

"The figures and author affiliation in this version have been changed."

§ These authors contributed equally to this work.

Received January 5, 2007; revised February 13, 2007; accepted February 16, 2007.


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