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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Aromatic amines

Cancer

Dermal

Genetic susceptibility

Genotoxicity

Occupational

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