DNA methylation changes in promoter region of CDKN2A gene in workers exposed in construction environment

Abstract

Purpose

Construction workers are exposed to a mixture of substances in the workplace considered carcinogenic. This study aimed to characterise gene-specific changes in DNA methylation over the workweek in this population as this type of environmental exposure has not been studied extensively.

Materials and methods

We evaluated their DNA methylation in 4 gene-promoter regions (CDKN2A, RASSF1A, MLH1 and APC) and 2 repeat elements (ALU and LINE-1) in blood samples obtained on the first and fifth day of the same workweek of a group of 39 male construction workers. DNA methylation was measured by bisulphite-PCR-Pyrosequencing. We also measured the levels of trace elements in the whole blood by ICP-MS.

Results

Only the CDKN2A gene had significant differences in the average methylation level between the first and fifth day of the workweek. We also observed that the levels of Cu, Pb, Se, Mn, and Ti decreased during the fifth day of exposure, and only lead, titanium and copper showed a low significant correlation with the methylation level mean for three specific CpG sites of the CDKN2A.

Conclusions

In summary, the data suggest that altered levels of CDKN2A methylation in construction workers may be a potential biomarker of recent exposure in this environment.

Keywords:

• CDKN2A
• suppressor gene
• occupational exposure
• metals
• biomarkers

Acknowledgements

We would like to thank Rui Reis, Adriane Feijó from Barretos Cancer Hospital and Mariana Brait from Johns Hopkins Medicine for assistance and opinion in this project and manuscript. We would like to thank Jeremy Squire for carefully proof-reading the English and for providing constructive criticism of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Authors would like to thank São Paulo Science Foundation [FAPESP proc. 2012/24279-1] and also [FAPESP proc. 2018/24069-3]. Furthermore, we thank Barretos Cancer Hospital and Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer Project), Campinas, Brazil, for partially funding the present for Scientific and Technological Development (CNPq, Brazil).