Organochlorine pesticides and epigenetic alterations in thyroid tumors

PurposeCancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients. MethodsOCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis. ResultsFurther TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P<0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P<0.001) and H4K16 (OR=6.03, P<0.001) acetylation. ConclusionThe current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.

Automated summary

The purpose of this study was to investigate the impact of organochlorine pesticides (OCPs) on the promoter methylation of tumor-suppressor genes and histone modifications in thyroid nodules. The results showed that Papillary thyroid carcinoma (PTC) patients had higher TSHR methylation and lower P16 methylation compared to benign thyroid nodule (BTN) patients. OCPs increased the methylation of TSHR and P16, and decreased the acetylation of H3K9, H4K16, and H3K18 in PTC patients. Conclusion: OCPs contribute to PTC progression by promoting TSHR hypermethylation and decreasing H3K9 and H4K16 acetylation. Assessing TSHR methylation and H3K9, H4K16 acetylation could be predictive in PTC patients.