Literature DB >> 24628370

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

T Skaaby1, L L N Husemoen, J P Thyssen, M Meldgaard, B H Thuesen, C Pisinger, T Jørgensen, K Carlsen, J D Johansen, T Menné, P B Szecsi, S Stender, A Linneberg.   

Abstract

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. Information 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 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma 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), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (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). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers.
CONCLUSIONS: The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses.
© 2014 British Association of Dermatologists.

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Year:  2014        PMID: 24628370     DOI: 10.1111/bjd.12969

Source DB:  PubMed          Journal:  Br J Dermatol        ISSN: 0007-0963            Impact factor:   9.302


  9 in total

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