title: Associations of filaggrin gene loss-of-function variants and human papillomavirus-related cancer and pre-cancer in Danish adults.
abstract: OBJECTIVE
  Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG) reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix.
  
  
  METHODS
  We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011.
  
  
  RESULTS
  There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years). There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7) for FLG mutation carriers vs. wild types.
  
  
  CONCLUSIONS
  FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.
authors.affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
authors.forename: Tea
authors.initials: T
authors.lastname: Skaaby
authors.affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
authors.forename: Lise Lotte N
authors.initials: LL
authors.lastname: Husemoen
authors.affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark; Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark; Faculty of Medicine, Alborg University, Alborg, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: Jeanne D
authors.initials: JD
authors.lastname: Johansen
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: Torkil
authors.initials: T
authors.lastname: Menné
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: Pal B
authors.initials: PB
authors.lastname: Szecsi
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Stender
authors.affiliation: Department of Epidemiology Research, National Center for Health Data and Disease Control, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bager
authors.affiliation: National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
authors.affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark; Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003718:Denmark; D005260:Female; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D012042:Registries
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins