Association of Base Excision Repair Gene hOGG1 Ser326Cys Polymorphism with Susceptibility to Cervical Squamous Cell Carcinoma and High-Risk Human Papilloma Virus Infection in a Chinese Population.

Abstract

This study investigated the association of the human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys polymorphism with risk of cervical squamous cell carcinoma (CSCC) and high-risk human papilloma virus (HR-HPV) infection. The hOGG1 Ser326Cys polymorphism is reported to be correlated with the risk of several cancers. However, there are reports that have found no significant differences in the frequency of the hOGG1 Ser326Cys between cervical carcinoma patients and controls. hOGG1 Ser326Cys was genotyped through modified allele mismatch amplification polymerase chain reaction in 1200 healthy controls, 400 cervical intraepithelial neoplasia (CIN) grade III cases, and 400 CSCC cases. The homozygous genotype of hOGG1 Cys326Cys (GG) was associated with increased risk of CIN III (odds ratio, OR = 1.81 [1.31-2.49], p < 0.001) and CSCC (OR = 3.05 [2.2-4.20], p < 0.001). The G allele or G carrier (GG + CG) genotype was a highly-significant risk factor for CSCC (OR = 1.49 [1.14-1.97], p = 0.004). In the HR-HPV-positive group, the homozygous genotype of hOGG1 GG was associated with increased risk of CSCC (OR = 3.66 [2.02-6.62], p < 0.001) and risk of CIN III (OR = 1.82 [1.08-3.06], p = 0.024). The proportion of G allele carriers was significantly increased in CIN III (51.9%, [322/620], OR = 1.33 [1.03-1.72], p = 0.028) and CSCC (62.1% [221/356], OR = 2.02 [1.51-2.71], p < 0.001). The GG and GC genotypes were consistently identified as significant risk factors for CSCC (OR = 1.73 [1.06-2.83], p = 0.029) in the HR-HPV infected group. We further observed enrichment of the hOGG1 Ser326Cys polymorphism in the CIN III (p = 0.021) and CSCC (p < 0.001) stratified by age at first intercourse, with more significant enrichment (p = 0.036) in the HR-HPV infection group. Our findings support associations of the hOGG1 Ser326Cys polymorphism with CSCC carcinogenesis and susceptibility to HR-HPV infection. The hOGG1 Ser326Cys polymorphism may serve as a potential genetic biomarker of susceptibility to cervical cancer and HR-HPV infection.