ctla-4 gene variations may influence cervical cancer susceptibility

CTLA-4 is the key player of the immune tolerance. Particular genotypes of ctla-4 have been reported to be associated with various diseases.

We aimed to evaluate the role of four single nucleotide polymorphisms (SNPs) of ctla-4 gene in cervical cancer.

55 patients and 110 healthy controls were genotyped for four polymorphic loci, three in promoter region; -1722(T/C), -1661(A/G), -318(C/T) and one in exon 1; +49(A/G) using PCR-ARMS and -RFLP methods.

At position -1661 the frequency of A/A homozygote and A allele were lower in patients than in controls. (P=0.01, P=0.035; respectively), while at position -318 the frequency of C/C homozygote and C allele were increased in patients (P=0.021, P=0.025; respectively). These significances, however, do not stand the Bonferroni correction suggesting that the effect of multiple comparisons should not be ignored. The haplotype analysis demonstrated 9 haplotypes, of which, 5 were observed in both groups with no significant different frequencies. The TGTA haplotype, however, was only observed in control group (9.54%, p=0.002) and the TGCG haplotype was only occurred in cervical cancer patients (6.48%, p=0.0003). The differences were still significant after Bonferroni correction.

As a conclusion TGTA haplotype as well as A allele at position -1661 might imply a protective role whereas TGCG haplotype as well as C allele at locus -318 might render susceptibility to cervical cancer. Investigation of ctla-4 gene variants in other ethnic populations will consolidate the findings of this study.