Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population
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Di Xiao1,*, Weihuang Huang1,*, Meiling Ou1, Congcong Guo1, Xingguang Ye1, Yang Liu1, Man Wang1, Baohuan Zhang1, Na Zhang1, Shiqi Huang1, Jiankun Zang5, Zixing Zhou1, Zihao Wen1, Chengli Zeng1, Chenfei Wu1, Chuican Huang1, Xiangcai Wei1,4, Guang Yang2,3, Chunxia Jing1,3
1Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
2Department of Parasitology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
3Key Laboratory of environmental exposure and health in Guangzhou, Jinan University, Guangzhou, Guangdong, China
4Family Planning Research Institute of Guangdong, Guangzhou, Guangdong Province, China
5Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
*These authors are contibuted equally to this work
Guang Yang, email: [email protected]
Chunxia Jing, email: [email protected]
Keywords: cGAS-STING, MHC, SNP, interaction, cervical precancerous lesions
Received: May 16, 2016 Accepted: September 25, 2016 Published: October 01, 2016
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 (ORadjusted = 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.
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