Common filaggrin gene mutations and risk of cervical cancer

TY - JOUR

T1 - Common filaggrin gene mutations and risk of cervical cancer

AU - Bager, Peter

AU - Wohlfahrt, Jan

AU - Sørensen, Erik

AU - Ullum, Henrik

AU - Høgdall, Claus Kim

AU - Palle, Connie

AU - Husemoen, Lise Lotte Nystrup

AU - Linneberg, Allan

AU - Kjaer, Susanne K

AU - Melbye, Mads

AU - Thyssen, Jacob P

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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).CONCLUSION: Carriage of FLG mutations was not associated with the risk of cervical cancer.

AB - 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).CONCLUSION: Carriage of FLG mutations was not associated with the risk of cervical cancer.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Denmark

KW - Female

KW - Heterozygote

KW - Humans

KW - Intermediate Filament Proteins

KW - Middle Aged

KW - Mutation

KW - Odds Ratio

KW - Regression Analysis

KW - Risk

KW - Uterine Cervical Neoplasms

U2 - 10.3109/0284186X.2014.973613

DO - 10.3109/0284186X.2014.973613

M3 - Journal article

C2 - 25383447

SN - 0284-186X

VL - 54

SP - 217

EP - 223

JO - Acta Oncologica

JF - Acta Oncologica

IS - 2

ER -