Interaction between polycyclic aromatic hydrocarbons and p16, FHIT gene CpG island methylation in patients with cervical intraepithelial neoplasias

Abstract

Objective: To explore the effect of polycyclic aromatic hydrocarbons (PAHs) and p16, FHIT gene CpG island methylation, as well as their interaction in cervical intraepithelial neoplasias. Methods: Objects of this study were from a cohort of cervical lesions study in Yangqu county of Shanxi province. All the patients were diagnosed pathologically, that including 83 patients with high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ), 86 patients with low-grade cervical intraepithelial neoplasia (CINⅠ) and another 91 women under normal cervical (NC) condition. 1-hydroxy pyrene in the urine was detected by high performance liquid chromatography (HPLC) while CpG island methylation status of tumor suppressor gene p16 and FHIT were measured by methylation-specifc polymerase chain reaction (MSP). Data were analyzed with Kruskal-Wallis H test, chi-square test and trend of chi-square test. Logistic regression models were used to estimate the odds ratio (OR) and corresponding 95% confidence intervals (95%CI) between influencing factors and the cervical disease by using the SPSS statistical software (version 20.0). The interaction under study was evaluated by using the generalized multifactor dimensionality reduction (GMDR) model. Results: Level of 1-hydroxy pyrene (H=50.743, P<0.001) and the high exposure rate of 1-hydroxy pyrene (trend χ(2)=20.146, P<0.001) were gradually increasing along with the severity of cervical intraepithelial neoplasia. The CpG island methylation rates of p16, FHIT in CINⅠand CINⅡ/Ⅲ group were higher than that in NC group, and gradually increasing along with the severity of cervical intraepithelial neoplasia (trend χ(2)=9.75, P=0.002; trend χ(2)=10.39, P=0.001). Results from the GMDR model showed that interaction existed among the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16, FHIT in CINⅠ and CINⅡ/Ⅲ group. Conclusion: Under the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16, FHIT appeared to have increased the risk of cervical intraepithelial neoplasia and causing synergistic effect in cervical intraepithelial neoplasia.