Abstract

Although persistence of high-risk human papillomavirus infection is the main risk factor, Glutathione S-Transferase highly polymorphic enzyme involved in the metabolism of xenobiotics, is a good candidate gene. The objective of this study was to compare the polymorphisms of Glutathione S-Transferase M1-null in women with cancerous lesions and without lesions. This study consisted of 322 uterine cervix samples of women from Mali and Burkina Faso with Cervical Intra-epithelial Neoplasia 2 and 3, adenocarcinoma and squamous cell carcinoma and 100 women with no lesions. Human Papillomavirus genotyping was performed by Real-time multiplex Polymerase Chain Reaction. Glutathione S-Transferase gene polymorphisms were determined using conventional Polymerase Chain Reaction followed by migration on agarose gel. A statistically significant association with high relative risks of 10.77 for the development of High grade Superficial or Squamous Intra-epithelial Lesion (95% CI = 5.59 - 20.72; p < 0.001), and 13.20 for cancer development (95% CI = 6.79 - 25.63; p < 0.001) was found in women with the null genotype of Glutathione S-Transferase M1 in the study population. In Burkina Faso and Mali, Glutathione S-Transferase M1-null presented relative risks of 9 and 11.05 for high-grade lesions, 15 and 11.40 for cancer. Similarly, significant results had been observed in women with human papillomavirus positive and human papillomavirus negative. The results of the present study support the idea that the deletion of Glutathione S-Transferase M1 plays a crucial role in the progression of high-grade lesions and cervical cancer.

Highlights

  • Human papillomavirus (HPV) infection, a sexually transmitted disease, is the leading risk factor for cervical cancer [1] [2]

  • High-risk human papillomaviruses are identified as the major causative agent of cervical cancer, viral clearance has been observed in some women

  • Women in the age group 35 - 44 were the most represented (31%). and those in the age group > 35 years old had a 3.33-fold higher risk for high grade squamous intraepithelial lesion (HSIL) or cancer

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Summary

Introduction

Human papillomavirus (HPV) infection, a sexually transmitted disease, is the leading risk factor for cervical cancer [1] [2]. In Burkina Faso and Mali, where the disease is the first most common diagnosed cancer, the incidence was estimated at 2517 and 2206 cases respectively with 2081 and 1704 deaths per year [6] [7]. High-risk human papillomaviruses are identified as the major causative agent of cervical cancer, viral clearance has been observed in some women. This suggests that other cofactors (environmental or genetic) play an important role in viral persistence leading to progression to carcinogenesis [10]. Phase II metabolite enzymes polymorphisms have been designated according to the literature as cofactors in the HPV infections progression to precancerous and cancerous lesions

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