AUTHOR=Huang Shiqi , Li Ruixin , Huang Xiuxia , Zheng Shaoling , Wang Lijun , Wen Zihao , Zou Xiaoqian , Wu Jing , Liu Yumei , Liu Dandan , Wang Yao , Dong Shirui , Chen Xiaojing , Zhu Kehui , Du Xiuben , Zhou Zixing , Han Yajing , Ye Xiaohong , Zeng Chengli , Zhang Baohuan , Yang Guang , Jing Chunxia 

TITLE=Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01123

DOI=10.3389/fgene.2019.01123

ISSN=1664-8021

ABSTRACT=<p>A case-control study was used to explore the association between the methylation status in the promoter regions of the <italic>cGAS</italic>, <italic>MAVS</italic>, and <italic>TRAF3</italic> genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The <italic>cGAS</italic>, <italic>MAVS</italic>, and <italic>TRAF3</italic> promoter methylation levels in CPL (CPL<italic><sub>cGAS</sub></italic> = 35.40%, CPL<italic><sub>MAVS</sub></italic> = 24.26%, and CPL<italic><sub>TRAF3</sub></italic> = 96.76%) were significantly higher than those in the control (Control<italic><sub>cGAS</sub></italic> = 31.87%, Control<italic><sub>MAVS</sub></italic> = 21.16%, and Control<italic><sub>TRAF3</sub></italic> = 96.26%, <italic>P<sub>cGAS</sub></italic>&lt; 0.001, <italic>P<sub>MAVS</sub></italic>&lt; 0.001, and <italic>P<sub>TRAF3</sub></italic> = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose <italic>cGAS</italic> methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (OR<sup>a</sup> = 2.49, 95% CI = 1.31-4.75, <italic>P</italic><sup>a</sup> = 0.006). The women with <italic>MAVS</italic> methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (OR<sup>a</sup> = 1.97, 95% CI = 1.06–3.69, <italic>P</italic><sup>a</sup> = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of <italic>cGAS</italic> and <italic>MAVS</italic> in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in <italic>cGAS</italic>, <italic>MAVS</italic>, and <italic>TRAF3</italic> genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in <italic>cGAS</italic> and <italic>MAVS</italic> genes and hrHPV infection might play a role in the development of CPL.</p>