Filaggrin loss-of-function mutations and incident cancer: A population-based study

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, since mutations are both associated with 10% higher serum vitamin D levels, which are possibly protective against cancer, and with impaired skin barrier function, which could lead to a higher cancer susceptibility.

OBJECTIVES: We investigated the association of the FLG genotype and specific types of cancers in four population-based cohorts.

METHODS: A total of 13,376 individuals were included and genotyped for selected common FLG mutations in Northern Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011. Persons with a history of cancer at baseline were excluded from the prospective analyses.

RESULTS: There were 1,339 incident cancers (median follow-up 11.4 years). The hazard ratios (HRs) and 95% confidence intervals, (95% CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR=0.95, 95% CI: 0.78, 1.16), any cancer excluding non-melanoma skin cancer (NMSC) (HR=1.05, 95% CI: 0.84, 1.31), head and neck cancer (HR=1.72, 95% CI: 0.71, 4.15), colorectal cancer (HR=0.82, 95% CI: 0.44, 1.52), cancer of bronchus and lung (HR=1.34, 95% CI: 0.77, 2.33), breast cancer (HR=0.58, 95% CI: 0.30, 1.14), cancer of the uterus (HR=0.42, 95% CI: 0.06, 3.10), prostate cancer (HR=1.09, 95% CI: 0.61, 1.94), urinary cancer (HR=1.30, 95% CI: 0.51, 3.29), malignant melanoma (HR=1.03, 95% CI: 0.41, 2.58) and NMSC (HR=0.70, 95% CI: 0.47, 1.05). In subgroup analyses of the participants over the age of 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers.

CONCLUSIONS: There were no statistically significant associations between FLG loss-of-function mutations and cancer except in subgroup analyses. This article is protected by copyright. All rights reserved.