Associations of Filaggrin Gene Loss-of-Function Variants and Human Papillomavirus-Related Cancer and PreCancer in Danish Adults

TY - JOUR

T1 - Associations of Filaggrin Gene Loss-of-Function Variants and Human Papillomavirus-Related Cancer and PreCancer in Danish Adults

AU - Skaaby, Tea

AU - Husemoen, Lise Lotte N

AU - Jørgensen, Torben

AU - Johansen, Jeanne D

AU - Menné, Torkil

AU - Szecsi, Pal B

AU - Stender, Steen

AU - Bager, Peter

AU - Thyssen, Jacob P

AU - Linneberg, Allan

PY - 2014/6/6

Y1 - 2014/6/6

N2 - PURPOSE: 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.

AB - PURPOSE: 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.

U2 - 10.1371/journal.pone.0099437

DO - 10.1371/journal.pone.0099437

M3 - Journal article

C2 - 24905740

SN - 1932-6203

VL - 9

SP - 1

EP - 9

JO - PloS one

JF - PloS one

IS - 6

M1 - e99437

ER -