Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population.

// Di Xiao 1, * , Weihuang Huang 1, * , Meiling Ou 1 , Congcong Guo 1 , Xingguang Ye 1 , Yang Liu 1 , Man Wang 1 , Baohuan Zhang 1 , Na Zhang 1 , Shiqi Huang 1 , Jiankun Zang 5 , Zixing Zhou 1 , Zihao Wen 1 , Chengli Zeng 1 , Chenfei Wu 1 , Chuican Huang 1 , Xiangcai Wei 1, 4 , Guang Yang 2, 3 , Chunxia Jing 1, 3 1 Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China 2 Department of Parasitology, School of Medicine, Jinan University, Guangzhou, Guangdong, China 3 Key Laboratory of environmental exposure and health in Guangzhou, Jinan University, Guangzhou, Guangdong, China 4 Family Planning Research Institute of Guangdong, Guangzhou, Guangdong Province, China 5 Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China * These authors are contibuted equally to this work Correspondence to: Guang Yang, email: guangyangphd@gmail.com Chunxia Jing, email: jcxphd@gmail.com Keywords: cGAS-STING, MHC, SNP, interaction, cervical precancerous lesions Received: May 16, 2016      Accepted: September 25, 2016      Published: October 01, 2016 ABSTRACT Human papillomavirus (HPV) infection is a definite risk factor for cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The cGAS-STING pathway in innate immunity plays an important role in protecting against HPV infection. Chen et al. described that the rs2516448 SNP in the MHC locus may affect susceptibility to cervical cancer, a finding that we attempted to replicate in a Chinese population. To investigate the effects of cGAS, STING and MHC polymorphisms on susceptibility to cervical precancerous lesions, 9 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions were also evaluated. We found a significantly decreased risk of cervical precancerous lesions for the GG genotype of rs311678 in the cGAS gene (OR adjusted = 0.40, 95% CI: 0.16−0.98). Moreover, MDR analysis identified a significant three-locus interaction model, involving HPV infection, age at menarche and rs311678 in cGAS. Additionally, a significant antagonistic interaction between HPV infection and rs311678 was found on an additive scale. In conclusion, our results indicate that the rs311678 polymorphism in the cGAS gene confers genetic susceptibility to cervical precancerous lesions. Moreover, the three-way gene-environment interactions further demonstrate that the rs311678 polymorphism in cGAS can significantly decrease the risk of HPV infection and the elder at menarche.