Genetic variants of filaggrin are associated with occupational dermal exposure and blood DNA alterations in hairdressers

Highlights: • Dermal exposure to chemicals increases hairdressers' risk for occupational cancer. • Genetic variants of skin barrier protein FLG could affect dermal uptake of chemicals. • Hairdressers carrying low-functional FLG have shorter telomeres than non-carriers. • Carriers of low-functional FLG have higher DNA methylation of cancer genes. • FLG variation is linked to cancer-related DNA changes that may influence cancer risk. -- Abstract: Hairdressers are exposed to high levels of chemicals, including possible carcinogens. For dermal exposure, the skin protects against the uptake of chemicals and the protein filaggrin (encoded by FLG) has a key role in skin barrier function. This study investigated if variants of FLG previously linked to impaired skin barrier function, i.e. null mutations and copy number variation (CNV) alleles (CNV10), are associated with cancer-related DNA changes. Blood and questionnaire data were collected from hairdressers (n = 295) and controls (n = 92). Exposure to aromatic amines was measured as hemoglobin adducts by gas chromatography tandem mass spectrometry. DNA from peripheral blood was used to test for FLG null mutations and CNV (10, 11, or 12 repeats), telomere length, and methylation of selected cancer-related genes. Hairdressers had a lower frequency of FLG null mutations (4.1 vs. 7.6%, P = 0.18) and CNV10 (43.2 vs. 56%, P = 0.0032) than controls. In hairdressers, CNV10 carriers had a decreased risk of high ortho-toluidine adducts in blood compared with non-carriers (odds ratio, OR = 0.49, 95% CI = 0.30–0.81). Further, telomere length was shorter for carriers of any FLG null allele (β = −0.18, 95% CI = −0.31 to −0.044) and CNV10 carriers (β = −0.054, 95% CI = −0.11 to −0.00051, linear regression adjusted for age, passive smoking, residence, and education) compared to non-carriers. Carriers of any FLG null allele showed higher methylation of the cyclin-dependent kinase inhibitor 2A gene CDKN2A (OR = 6.26, CI = 1.13–34.7), but not of the other genes analyzed. These associations were not found among the controls. Our study showed that the frequency of FLG CNV10 was lower among hairdressers than controls, which may indicate a healthy worker selection. Moreover, FLG null and CNV10 were associated with cancer-related DNA changes in hairdressers, which may influence their risk of cancer.