Role of ganglioside biosynthesis genetic polymorphism in cervical cancer development

Abstract

Cervical cancer is the most common gynaecological cancer in women. Cell mediated immunity plays a significant role in the progression or regression of neoplastic cervical lesions caused by human papilloma virus infection. Engagement of antigen-specific T cell receptors is a prerequisite for T cell activation. The initial events of T cell activation involve the movement of the T cell receptor into specialised microdomains known as lipid rafts. Gangliosides play an active role in the formation, stabilisation and biological functions of lipid rafts. This study aims to determine whether polymorphisms in the genes involved in the biosynthesis of gangliosides represent risk a factor for cervical cancer.Taqman methods for single nucleotide polymorphism genotyping was used. All subjects carried the homozygous wild-type genotypes for all analysed genes (CC for gene <i>B4GALT5</i>, AA for gene <i>ST3GAL5</i>, AA for gene <i>ST8SIA1</i> and CC for gene <i>B4GALNT1</i>). A χ2 test showed significant differences in genotype failure for <i>B4GALT5</i> rs138960078 (χ2 = 32.02, df = 1, <i>p</i> = .001) and genotype failure for <i>B4GALNT1</i> rs144643461 (χ2 = 41.03, df = 1, <i>p</i> = .001) between cervical cancer group and control group. Genotype failures were significantly more frequent in the cervical cancer group. Unknown adjacent SNPs to rs138960078 in gene <i>B4GALT5</i> and rs144643461 in gene <i>B4GALNT1</i> could be associated with cervical cancer development.IMPACT STATEMENT<b>What is already known on this subject?</b> Individual genetic factors play an important role in the pathogenesis of disease. In recent years, the different SNPs and their potential effects on CC risk have been extensively studied. A large number of single nucleotide genetic variants associated with cervical cancer have been identified.<b>What do the results of this study add?</b> Our results suggest the presence of unknown adjacent SNPs to rs138960078 in gene B4GALT5 and rs144643461 in gene B4GALNT1 that could be associated with cervical cancer development.<b>What are the implications of these findings for clinical practice and/or further research?</b> Better understanding of causal-consequence relationship between ganglioside biosynthesis and TCR mediated activation with consequently cervical cancer development is needed. Our research opens a new possibilities for identification of polymorphisms in the genes involved in the biosynthesis of gangliosides which can be a risk factor for cervical cancer development.