Abstract 2514: The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia.

Abstract

Abstract A positive association between solar UV exposure and micronuclei (MN) frequency (biomarker of chromosome breakage or loss) was previously reported with the effect of solar UV exposure on DNA damage greater when serum vitamin D (25(OH)D) levels were insufficient (<50nmol/L). MN formation can result from global hypomethylation of the DNA repeat sequence, which is suggested to be a significant factor in driving oncogenesis. Therefore the aim was to evaluate the relationship between lymphocytic DNA methylation pattern in LINE-1 repetitive elements and solar UV exposure in 208 male and female participants from South Australia. Possible modifying effects of serum 25(OH)D levels were examined. Personal solar UV exposure was estimated from hours of outdoor exposure over 16 weeks recalled at the time of blood collection. DNA methylation pattern in LINE-1 repetitive elements was assessed in peripheral blood lymphocytes using pyrosequencing. DNA methylation in LINE-1 repetitive elements decreased with increasing sun exposure (% decrease=0.5% per doubling of sun exposure; 95%CI: -0.7-0.2 pvalue=0.00003). There was no correlation between LINE-1 methylation and MN frequency, however for every 1% increase in LINE-1 methylation there was a corresponding 4.3% (95% CI:0.6-8.1 p-value=0.02) increase in nucleoplasmic bridges (biomarker of dicentric chromosome formation) and a 4.3% increase in necrosis (CI:1.9-6.8 p-value=0.0005). This suggests that the reduction in LINE-1 methylation with increased solar exposure may be too small to explain increases in MN frequency and therefore other mechanisms must be considered. There was no clear relationship between 25(OH)D and DNA methylation. In conclusion, the inverse relationship between solar UV radiation and LINE-1 DNA methylation status suggests a role for solar UV exposure in influencing genomic methylation patterns, which in turn appears to be associated with specific biomarkers of cell death (necrosis) and chromosomal stability (NPBs). If this holds true, then the use of LINE-1 hypomethylation, and possibly methylation of other sequences such as Alu repeats, as a biomarker for studying the role of UV in inducing both skin and internal cancers (and other diseases) might deserve further consideration. Citation Format: Visalini Nair-Shalliker, Varinderpal Dhillon, Mark Clements, Bruce K. Armstrong, Michael Fenech. The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2514. doi:10.1158/1538-7445.AM2013-2514