STUDY OF NUCLEOTIDE VARIABILITY WITH THE MITOCHONDRIAL COX I GENE FROM CANCEROUS TISSUES IN SENEGALESE PATIENTS WITH CERVICAL CANCER

Background: Cervical cancer is the first gynecological cancer in Senegal with 1,195 new cases per year and an annual mortality of around 66% (LISCA, 2019). Mitochondrial involvement in the process of apoptosis and tumorigenesis has been analyzed previously from different cancer, and from analyses, 21 sites polymorphisms of the Cox genes (including CoxI, CoxII and CoxIII) contributed to dysfunction of mitochondrial respiratory function and have been associated with sensitivity to cancers such as prostate cancer(Green, 1998)(Cavali and Liang, 1998). These data stimulated interest in examining the potential role of mtDNA mutation of host inprogression and maintenance to cancer stades.The aim of thisstudy is to analyse the polymorphism of COXI gene from biopsies of cervical cancer in Senegalese subjects. Methods: In this study, polymorphisms of mitochondrial Cox1 gene were highlighted in 65 patients with cervical cancer women admitted to Aristide Hospital Le Dantec-Julio Curie Institute. Clinical and socidemographical data wer recorded.The total DNA of the tissues was extracted using the Standard Qiagen method (Kit QiagenDneasy Tissue), and subsequently used as template for polymerase chain reaction (PCR). At all 65 CoxI sequences were edited by Genalys PPC V.5.0.03, -Masasumi et al, 1996), BioEdit version 7.2.0 software (Hall, 1997) and ClustalW algorithm (Thomson et al., 1994).Genetic parameters were determined using DnaSP v5.10,MEGA v7.0.26, MEGA v 7.0.26, and Arlequin V 3.5.13 softwares were used to determine genetic parameters. Genetic variation variation according to epidemiological parameters were deterlined using Fst values (index of genetic differenciation and genetic structure (AMOVA) were determined using Arlequinversion 3.5.13 Results:167 variations including 163 substitutions and 4 deletions were found. Of these, 19 have already been described in other studies and deposited in the MITOMAP database. The Mitochondrial haplogroup U is the most common African haplogroup in this study. 58 transitions sites and 41 transversions sites of CoxI were recored. In this gene, it appears that the haplotypic diversity is higher (Hd = 0.9931 +/- 0.048) than that of the nucleotide (Pi) which has a value equal to 0.09227 +/- 0.045. Analysis of the mismatch distribution curves (Fig 1) of cancerous tissues under the assumption of an expanding population gives a multimodal appearance Discussion and Conclusion: Genetic events leading to transformation from a normal cell to a cancer phenotypeappear to be multiple. Human papilloma viruses (HPV) are probably involved in the initiation of cancer and perhaps in the maintenance of the malignant state. However, for the sake of controlling this cancer, it is necessary to identify different variants within the host cell (the woman) which could be responsible for maintaining the malignant state and the occurrence of this cancer. Our study reveals a high variability of Cox1 gene, and could be useful for an establishment of a sensitive and rapid genetic screening test.