Common filaggrin gene mutations and risk of cervical cancer.
BACKGROUND
As carriers of filaggrin gene (FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer.


METHODS
We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage.


RESULTS
The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59).


CONCLUSIONS
Carriage of FLG mutations was not associated with the risk of cervical cancer.
Department of Epidemiology Research, Statens Serum Institut , Denmark.
Peter
P
Bager
Jan
J
Wohlfahrt
Erik
E
Sørensen
Henrik
H
Ullum
Claus Kim
CK
Høgdall
Connie
C
Palle
Lise Lotte Nystrup
LL
Husemoen
Allan
A
Linneberg
Susanne K
SK
Kjaer
Mads
M
Melbye
Jacob P
JP
Thyssen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D000091344:Filaggrin Proteins; D006579:Heterozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D012044:Regression Analysis; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins