IL-6 597A/G (rs1800797) and 174G/C (rs1800795) Gene Polymorphisms in the Development of Cervical Cancer in Lithuanian Women.

Agne Vitkauskaite,Vijoleta Juseviciute,Daiva Vaitkiene,Gabriele Samuolyte,Joana Celiesiute,Erika Skrodeniene,Kristina Jariene,Ruta Jolanta Nadisauskiene

doi:10.3390/medicina57101025

Agne Vitkauskaite, Vijoleta Juseviciute + Show 6 more

Open Access

https://doi.org/10.3390/medicina57101025

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Abstract

Our study aimed to evaluate the distribution of genotypes and allele frequencies of IL-6 597A/G (rs1800797) and 174G/C (rs1800795) polymorphisms in HPV infected and uninfected healthy women and cervical cancer patients. A PCR based Multiplex HPV genotyping test kit was used for in vitro detection and differentiation of high risk HPV genotypes. Genotyping of two polymorphisms, IL-6 597A/G (rs1800797) and 174G/C (rs1800795), was performed using the KASP genotyping assay kit. Cervical cancer patients were more likely to be HPV positive than control patients. Allele C of IL-6 rs1800795 was associated with a higher risk of cervical cancer by 2.26-fold and genotype CC by 5.37-fold. Genotype CC of IL-6 rs1800795 was more frequent in the HPV positive group compared with the HPV negative group (p = 0.002). Allele G of IL-6 rs1800797 was more frequently found in women with HPV16/HPV18 compared to other HPV types (p = 0.045). Women with AA genotypes of IL-6 rs1800797 were less frequently infected with HPV16/HPV18 compared to other HPV types (p = 0.045). The major finding of the study is the significant association of C allele and CC genotype of IL-6 1800795 gene with cervical cancer in the Lithuanian population. Genotype CC of IL-6 rs1800795 has a significant association with HPV infection as well.

Highlights

Cervical cancer remains a major health problem worldwide, especially in Lithuania, where morbidity and mortality rates are one of the highest among all Baltic countries [1]
Allele C of Interleukin 6 (IL-6) rs1800795 and genotype CC of IL-6 rs1800795 were more frequent among women with cervical cancer than in controls (74.2% vs. 56%, p < 0.012 and 29.2% vs. 7.1%, p < 0.001 respectively)
Allele C of IL-6 rs1800795 was associated with higher risk by 2.26-fold, and genotype CC was associated with higher risk by 5.37-fold of cervical cancer

Summary

Introduction

Cervical cancer remains a major health problem worldwide, especially in Lithuania, where morbidity and mortality rates are one of the highest among all Baltic countries [1]. It is proven that cervical intracellular squamous epithelium abnormalities and cancer are closely related to persisting human papillomavirus (HPV) infection. The persistence of infections by high-risk HPV types is the single most significant risk factor for malignant progression [2]. This virus infects the epithelium exclusively, replicating only in fully matured epithelium cells, affects standard cell cycle control, and promotes an uncontrollable cell division, causing genetic damage [3]. HPV infection alone is not enough for complicated processes of cellular change, and it is not always possible to make the association between HPV infection and cervical intracellular squamous epithelium abnormalities [4]. The changes of cytokines are most likely cervical cancer-related and support the hypothesis of systemic inflammation in cervical cancer [7]

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