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Association of TNF-308 G>A polymorphism located in tumor necrosis factor a with the risk of developing cervical cancer and results of pap smear
Authors:Nooshin Babapour  Mehrane Mehramiz  Azam Rastgar Moghadam  Negin Behboodi  Zohre Yousefi  Mona Maftouh  Sahar Talebian  Majid Khazaei  Amirhosein Jafarian  Noorieh Sharifi-Sistani  Amir Avan  Malihe Hasanzadeh
Affiliation:1. Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Department of Gynecology Oncology, Woman Health Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Nooshin Babapour, Mehrane Mehramiz, Azam Rastgar Moghadam, and Negin Behboudi contributed equally to this study.;2. Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;3. Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Nooshin Babapour, Mehrane Mehramiz, Azam Rastgar Moghadam, and Negin Behboudi contributed equally to this study.;4. Department of Gynecology Oncology, Woman Health Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;5. Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;6. Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract:Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF-308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®-probes-based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval CI]: 1.57-4.83, <0.001) and OR of 7.27 (95%CI: 2.5-20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF-308 G>A located on TNF-a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.
Keywords:cervical cancer  cytokine  rs1800269  tumor necrosis factor a (TNFa)
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