title: Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population.
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 (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.
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Weihuang
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Ou
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Baohuan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Zang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Zixing
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Chengli
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Chuican
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.|Family Planning Research Institute of Guangdong, Guangzhou, Guangdong Province, China.
authors.forename: Xiangcai
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Parasitology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.|Key Laboratory of environmental exposure and health in Guangzhou, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.|Key Laboratory of environmental exposure and health in Guangzhou, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Jing
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009713:Nucleotidyltransferases / Q000235:genetics*; D030361:Papillomavirus Infections / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000208:ethnology / Q000235:genetics / Q000821:virology; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D008565:Membrane Proteins; D009713:Nucleotidyltransferases; C532857:STING1 protein, human; D000099197:STING Protein; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: MHC; SNP; cGAS-STING; cervical precancerous lesions; interaction