Implication of the Cytochrome <i>P-450c17α</i> (<i>CYP17α</i>) Gene in the Tumor Progression of Uterine Fibroids in Senegalese Women

Abstract

Uterine fibroids, also known as leiomyomas, uterine myomas or fibroleiomyomas, are benign, encapsulated uterine tumors consisting of smooth muscle fibers of the uterus and connective tissue, the most common in the female genital tract. They affect 20 to 25% of women of childbearing age and are 3 to 9 times more common in black women than in white women, and nearly 70% of those close to 50 years of age. Uterine myomas are a real public health problem. The cost of treating them is expensive and the only treatment deemed effective is surgery. The rapid progression of leiomyomas during the childbearing years and regression after menopause indicate that estrogen plays a key role as a growth factor for these tumors. To contribute to the knowledge of the etiological factors involved in the tumor process of uterine fibroids, the study of the <i>Cytochrome P-450c17α</i> gene (<i>CYP17α</i>), involved in the hydroxylation of estrogen, has been carried out. Our study population consisted of 57 patients with uterine fibroids. After sampling (tumour tissue and peripheral blood), molecular analysis were done (DNA extraction, PCR-sequencing). Raw data were submitted to Mutation Surveyor 5.0.1 for mutation identification and AlamutVisual 2.12 software. The pathogenicity of each non-synonymous mutation was evaluated using Polyphen-2, Mutation Taster and SIFT. After cleaning, correction and alignment of sequences with BioEdit 7.0.8.0, genetic diversity, genetic differentiation and polymorphism of the gene <i>CYP17α</i> in correlation with epidemiological factors were determined with DNASP 5.10.01, MEGA 7.0.14, Arlequin 3.5.3.1 and the statistical software RStudio 3.5.1. Our results showed 84 mutations characterizing a high rate of tumor tissue polymorphism but also a genetic difference between tumor and peripheral blood. The mutation c.-34T>C which is located in the 5' promoter region at 34 bp upstream of the translation initiation site was found in patients with uterine fibroids. No genetic structuring of the <i>CYP17α</i> gene according to clinico-pathological parameters was observed. In conclusion, the cytochrome P450 enzymes responsible for highly specific reactions in the steroid biosynthesis pathway are gaining interest as molecular targets, given their role clé́ in the formation of various very potent endogenous steroid hormones. Indeed, current treatments for tumors, particularly fibroids, are mainly surgical and expensive. It is therefore essential to develop and evaluate alternatives to surgical procedures.