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Associations of filaggrin gene loss-of-function variants and human papillomavirus-related cancer and pre-cancer in Danish adults.

Skaaby T, Husemoen LL, Jørgensen T, Johansen JD, Menné T, Szecsi PB, Stender S, Bager P, Thyssen JP, Linneberg A - PLoS ONE (2014)

Bottom Line: 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.Participants were genotyped for the most common FLG mutations in Europeans.

View Article: PubMed Central - PubMed

Affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.

ABSTRACT

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.

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Related in: MedlinePlus

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Mentions: We included a total of 13,376 persons with FLG genotype: 2,577, 6,247, 1,206, and 3,346 participants from the Monica10, the Inter99, the Allergy98, and the Health2006 study, respectively (Figure 1).


Associations of filaggrin gene loss-of-function variants and human papillomavirus-related cancer and pre-cancer in Danish adults.

Skaaby T, Husemoen LL, Jørgensen T, Johansen JD, Menné T, Szecsi PB, Stender S, Bager P, Thyssen JP, Linneberg A - PLoS ONE (2014)

Flowchart
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048243&req=5

pone-0099437-g001: Flowchart
Mentions: We included a total of 13,376 persons with FLG genotype: 2,577, 6,247, 1,206, and 3,346 participants from the Monica10, the Inter99, the Allergy98, and the Health2006 study, respectively (Figure 1).

Bottom Line: 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.Participants were genotyped for the most common FLG mutations in Europeans.

View Article: PubMed Central - PubMed

Affiliation: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus