Carcinogenesis Advance Access originally published online on March 6, 2007
Carcinogenesis 2007 28(6):1237-1240; doi:10.1093/carcin/bgm043
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CTLA-4 gene and susceptibility to human papillomavirus-16-associated cervical squamous cell carcinoma in Taiwanese women
1 Department of Gynecology and Obstetrics, Mackay Memorial Hospital, 45, Min-Sheng Road, Tamshui 25115, Taipei, Taiwan
2 Department of Medical Research, Mackay Memorial Hospital, 45, Min-Sheng Road, Tamshui 25115, Taipei, Taiwan
3 Department of Pediatrics, Mackay Memorial Hospital, 45, Min-Sheng Road, Tamshui 25115, Taipei, Taiwan
4 Mackay Medicine, Nursing and Management College, Taipei 11260, Taiwan
5 Department of Gynecology and Obstetrics, Taipei Medical University, Taipei 11031, Taiwan
6 Department of Pediatrics, Taipei Medical University, Taipei 11031, Taiwan
* To whom correspondence should be addressed. Tel: +886 2 28094661 ext. 3049; Fax: +886 2 28094679; Email: 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 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, 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.
Abbreviations: CSCC, cervical squamous cell carcinoma; CTLA-4, cytotoxic T-lymphocyte antigen-4; 95% CI, 95% confidence interval; HPV, human papillomavirus; HWE, Hardy–Weinberg equilibrium; OR, odds ratio; SNP, single-nucleotide polymorphism
These authors contributed equally to this work. Received January 5, 2007; revised February 13, 2007; accepted February 16, 2007.
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