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Identifying environmental factors and their relationship with epigenetic alterations is essential for understanding cancer, a leading cause of death. Currently, cancer screening and early detection development efforts are ongoing and epigenetics-based tests are one of the top choices as strategies. The understanding of how these alterations behave in cancer-free (CF) populations with well annotated data is essential. We randomly selected 601 saliva specimens from two Brazilian countrywide epidemiological studies POP-Brazil and SMESH. Extracted DNAs were sodium bisulfite converted and analyzed by Quantitative Methylation-Specific PCR (QMSP). Five genes previously reported as DNA methylation prone in cancer were selected (ITGA4, EDRNB, PAX5, p16, CCNA1). All participants were interviewed and provided sociodemographic and sexual behavior information as well as genital (gn) and oral biological samples. Variables were categorized and Fisher’s exact test was performed using SAS 9.4. Surprisingly, methylation in 3 cancer associated genes showed considerable frequencies in this CF group. DNA methylation was observed for EDNRB in 75/601 samples (12.5%), PAX5 in 55/601 (9.2%), and ITGA4 in 20/601 (3.3%). 12 samples displayed concomitant methylation on 2 of these 3 genes. p16 and CCNA1 methylation were only present in 1 sample each. Preliminary analyses suggest that specific genes methylation are observed with the presence of low (LR) and high-risk (HR) HPV types. EDNRB methylation groups with the presence of HR HPV type 16, 31, 39, 51, 58 and 59 from gn samples and LR types 6 and 42. ITGA4 methylation and HR HPV types 16 and 59 were detected in oral samples, and types 52, 56 and 68 in gn samples, as well as LR HPV types 40 and 42. In people with early onset of smoking, EDNRB and PAX5 seem to be more frequently methylated. The positivity of PAX5 was higher in participants who smoke, use alcohol and presented a positive diagnosis of syphilis and/or HIV. PAX5 methylation was more frequent in HR HPV 33, 58, 68 and 62 and LR type 6. Further analyses are ongoing. Our study shows methylation in cancer related genes in a CF population. The variables collected include some proven cancer risk factors and others still unknown, thus lead us to uncover directions to identify main cancer related players in a Brazilian population. The presence of cancer related alterations may indicate premalignant stages, exposure and lifestyle consequences, both at the same time or separately. In our pilot analysis, different types of HPV seem to correlate with epigenetic changes, this could bring attention to less studied HPV types and their role in carcinogenesis. Additional analyses of the current data and larger prospective, population-based studies, assessing the use of salivary DNA methylation in cancer-free and cancer groups of subjects are needed to explore the current findings and dissect the potential of saliva as a means of tracking cancer related changes. Citation Format: Ana Paula Muterle Varela, Dieila Giomo De Lima, Laura Palmieri, Juliana Comerlato, Fernando Hayashi Sant’Anna, Isabel C Bandeira, Marina Bessel, Pedro Isaacsson Velho, Eliana M. Wendland, Mariana Brait. HPV status and epigenetic profiling of saliva from a cancer-free population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6528. |
