Pathogenicity of CYP17α mutations in the occurence of uterine fibroids and breast fibroadenomas

Bineta Keneme Bineta Keneme,Pape Mbacké Sembene Pape Mbacké Sembene

doi:10.30574/ijbpsa.2021.1.2.0030

Bineta Keneme Bineta Keneme, Pape Mbacké Sembene Pape Mbacké Sembene

Open Access

https://doi.org/10.30574/ijbpsa.2021.1.2.0030

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Abstract

Background. Uterine fibroids and breast fibroadenomas are a real public health problem. Despite the efforts made, the etiological factors are still unknown. In addition, these tumors share histopathological similarities, including a higher prevalence in black women. To better understand the factors involved, we set out to assess the genetic characteristics of uterine fibroids and breast fibroadenomas in Senegalese women using CYP17α genes. Results. For the CYP17α gene, 196 mutations were found among which, 65 are specific to uterine fibroids, 112 mutations specific to breast fibroadenomas and 19 common to both pathologies. Analysis of the pathogenicity of missense mutations reveals that many mutations are considered to be a simple polymorphism and 21 non-synonymous mutations appear to be potentially damaging, including 6 specific to patients with uterine fibroids; 14 found in patients with breast fibroadenomas. Conclusion. As a genetic marker of risk, the codons 12, 17, 20, 60 and 72 of CYP17α can be a tool to identify high-risk groups of women for prevention and treatment protocols.

Highlights

Uterine fibroids affect 20 to 25% of women in reproductive activity and almost 70% of aged 50 years [1]
Analysis of the pathogenicity of missense mutations reveals that many mutations are considered to be a simple polymorphism and 21 non-synonymous mutations appear to be potentially damaging, including 6 specific to patients with uterine fibroids; 14 found in patients with breast fibroadenomas
The c.3G>A mutation alters the 1st amino acid of exon 1 of the CYP17α gene, namely methionine and results in the loss of the codon that initiates translation. This loss could result in inhibition of the synthesis of the enzyme CYP17A1 and blockade of 17α-hydroxylase and 17,20-lyase activities in patients with this polymorphism. This is further confirmed by the discovery of the c.5G>A (p.Trp2*) and c.51G>A (p.Trp17*) variants that we found respectively in patients with uterine fibroids and those with breast fibroadenomas

Summary

Introduction

Uterine fibroids affect 20 to 25% of women in reproductive activity and almost 70% of aged 50 years [1]. According to Okolo [2], fibroids affect millions of women around the world and occur, in 60% of cases, in women aged 45 years. This prevalence varies by race, with women of African ethnicity being at greater risk. Uterine fibroids are associated with significant morbidity and constitute a real public health problem. Uterine fibroids and breast fibroadenomas are a real public health problem. These tumors share histopathological similarities, including a higher prevalence in black women. To better understand the factors involved, we set out to assess the genetic characteristics of uterine fibroids and breast fibroadenomas in Senegalese women using CYP17α genes

Methods

Results

Discussion

Conclusion