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.

Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?

“…Previously we have shown an association between this promoter polymorphism and B-cell chronic lymphocytic leukemia [30]. Moreover, it was found by us and others that the same allele confers susceptibility to female-related cancers: sporadic breast cancer [31,48], and cervical cancer [29,32] as well as non-small cell lung cancer in women [24]. In contrast to our results CTLA-4g.319C>T polymorphism was not associated with lung cancer (without stratification by gender) [41] or other cancers, such as colon cancer [42], colorectal cancer [52] or multiple myeloma [44].…”

“…Interestingly, the opposite results for this SNP were shown for mucosa-associated lymphoid tissue lymphoma [43] and multiple myeloma [44], while no associations with cancer risk were observed for colorectal cancer [45], chronic lymphocytic leukemia [30], cervical squamous cell carcinoma [29], malignant melanoma [46], or non-malignant melanoma [47].…”

“…The polymorphisms in co-stimulatory molecule genes were shown to be genetic susceptibility factors for several human cancers [27][28][29][30][31][32], therefore we hypothesized that they might influence susceptibility to prostate cancer in Polish population.…”

Polymorphism analysis of the CTLA-4 gene in paracoccidioidomycosis patients

“…These data are consistent with a report by Kouki et al (2000), in which +49G reduces CTLA-4 expression and thus enhances the immune response. Recently, Su et al (2007) investigated CTLA-4 polymorphisms and their relation to squamous cell carcinoma. The -318T allele was more often found in women infected by the human papilloma virus than in healthy women, which led them to postulate that this SNP could be implicated in the persistence of the virus, which causes cervical carcinoma.…”

Association between the cytotoxic T-lymphocyte antigen 4-318C/T polymorphism and malignant tumor risk

“…CTLA-4 polymorphisms have been demonstrated to be associated with increased susceptibility to various malignant tumors in a number of different ethnic populations. Previous studies have been performed to determine whether the -318 cytosine/thymine (-318C/T) polymorphism was involved in the etiology of various malignant tumors in Asian population (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). However, the results from these studies remain inconclusive and conflicting.…”