Residential exposure to radon and DNA methylation across the lifecourse: an exploratory study in the ALSPAC birth cohort

Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786 to 980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although chance and residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.