LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia.

BACKGROUND: Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women. METHODS: Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion. RESULTS: Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01-1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%). CONCLUSIONS: LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.

Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily.

OBJECTIVES: Host factors, including genetic polymorphisms, may explain some of the individual differences in cervical cancer occurrence, and susceptibility information may be useful to address effective and specific preventive strategies for different countries. The purpose of the present study was to investigate the role of p53 codon 72, glutathione S-transferase class mu (GSTM1), glutathione S-transferase class theta (GSTT1), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms on the risk for infection and/or of cervical intraepithelial lesions in women attending a colposcopy service in Catania, Sicily, with an already reported high prevalence of human papillomavirus. METHODS: To identify the association among individual genetic polymorphisms, human papillomavirus infection, and histological findings, a case-control study was designed. Furthermore, to assess the combined effects of these polymorphisms on cervical cancer risk, combined genotype frequencies were compared among case patients and controls. RESULTS: Women homozygous for the p53 codon 72 Arg genotype were at a 5.6-fold higher risk for developing cervical intraepithelial neoplasia (CIN) 2 or 3 compared with those showing homozygosity for the Pro genotype or heterozygosity for the Pro/Arg genotype. The GSTM1 and GSTT1 null genotypes were overrepresented in infected patients and in women with CIN 2 or 3, although without any significant associations. A decreased risk for CIN of individuals homozygous for the MTHFR T allele was shown. CONCLUSIONS: After multiple logistic analyses, the presence of the allele 677T of the MTHFR gene was the best explaining protective factor against cervical carcinogenesis, and the allelic distribution in the control group followed the Hardy-Weinberg equilibrium expectations. However, the findings of our study still remain to be confirmed by additional and larger population-based surveys.

Human papillomavirus infection: low-risk and high-risk genotypes in women in Catania, Sicily.

INTRODUCTION: Human papillomavirus (HPV) infection has been strongly and consistently associated with cervical carcinoma and its cytologic precursors, such as squamous intraepithelial lesions. A cross-sectional survey was conducted with the aim of estimating the prevalence of cervical HPV infection in women attending a service of colposcopy in Catania, Eastern Sicily, Italy. METHODS: The prevalence of type-specific HPV was examined in women with negative colposcopic results and cervical intraepithelial neoplasia grades 1, 2, or 3, with the aim of providing some cross-sectional figures on the local epidemiology of HPV infection. RESULTS: Human papillomavirus DNA was found in 62.1% of women with negative colposcopic results and in 73.2% with positive colposcopic results. Among high-risk types, a predominance of HPV-16 (51.5% of infected women) was shown followed by HPV-56 (29.7%). An age-related pattern was described with a peak in HPV prevalence among women younger than 25 years, followed by the expected decline in prevalence and a second characteristic peak in the perimenopausal or postmenopausal years, useful to design future control strategies. CONCLUSIONS: The age-related pattern of HPV prevalence and the presence of uncommon high-risk genotypes and their role in the pathogenesis of cervical cancer need to be addressed by specific epidemiologic studies to design large-scale screening programs and multivalent vaccine strategies.