EPIDEMIOLOGY AND HEALTH SERVICES RESEARCH BJD British Journal of Dermatology Filaggrin loss-of-function mutations and incident cancer: a population-based study T. Skaaby, 1 L.L.N. Husemoen, 1 J.P. Thyssen, 2 M. Meldgaard, 3 B.H. Thuesen, 1 C. Pisinger, 1 T. Jørgensen, 1,4,5 K. Carlsen, 1 J.D. Johansen, 3 T. Menn e, 3 P.B. Szecsi, 3 S. Stender 3 and A. Linneberg 1,6,7 1 Research Centre for Prevention and Health, Glostrup University Hospital, Nordre Ringvej 57, DK-2600, Glostrup, Denmark 2 National Allergy Research Centre, Department of Dermato-allergology and 3 Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hell- erup, Denmark 4 Faculty of Health Science and 7 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 5 Faculty of Medicine, Alborg University, Alborg, Denmark 6 Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark Correspondence Tea Skaaby. E-mail: tea.skaaby.01@regionh.dk Accepted for publication 10 March 2014 Funding sources None. Conflicts of interest None declared. DOI 10.1111/bjd.12969 Summary Background Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. Objectives To investigate the association of the FLG genotype and cancer types in four population-based cohorts. Methods A total of 13 376 individuals were genotyped for FLG mutations. Infor- mation on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. Results There were 1339 incident cancers (median follow-up 11Á4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0Á95, 95% CI 0Á78–1Á16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1Á05, 95% CI 0Á84–1Á31), head and neck cancer (HR 1Á72, 95% CI 0Á71–4Á15), colorectal cancer (HR 0Á82, 95% CI 0Á44–1Á52), bronchus and lung cancer (HR 1Á34, 95% CI 0Á77– 2Á33), breast cancer (HR 0Á58, 95% CI 0Á30–1Á14), uterine cancer (HR 0Á42, 95% CI 0Á06–3Á10), prostate cancer (HR 1Á09, 95% CI 0Á61–1Á94), urinary can- cer (HR 1Á30, 95% CI 0Á51–3Á29), malignant melanoma (HR 1Á03, 95% CI 0Á41–2Á58) and NMSC (HR 0Á70, 95% CI 0Á47–1Á05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all can- cers and NMSC among FLG mutation carriers. Conclusions The only significant associations between FLG loss-of-function muta- tions and cancer were in subgroup analyses. What’s already known about this topic? • Loss-of-function mutations in the filaggrin gene (FLG) affect 8–10% of Northern Europeans and result in ichthyosis vulgaris and high risk of atopic dermatitis. • The impaired skin barrier in FLG mutation carriers is associated with 10% higher serum vitamin D levels. What does this study add? • Apart from a borderline-significant lower risk of nonmelanoma skin cancer among filaggrin mutation carriers, the filaggrin genotype was not associated with cancer incidence except in subgroup analyses. © 2014 British Association of Dermatologists British Journal of Dermatology (2014) 171, pp1407–1414 1407