Skaaby Tea, Husemoen Lise Lotte N, Jørgensen Torben, Johansen Jeanne D, Menné Torkil, Szecsi Pal B, Stender Steen, Bager Peter, Thyssen Jacob P, Linneberg Allan
Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
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.
PLoS One. 2014 Jun 6;9(6):e99437. doi: 10.1371/journal.pone.0099437. eCollection 2014.
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.
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.
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.
FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.
丝聚合蛋白在皮肤、口腔、食管和宫颈黏膜中表达。丝聚合蛋白基因（FLG）的功能丧失突变会降低丝聚合蛋白的表达，并导致皮肤屏障功能受损。我们推测，FLG突变携带者更容易感染人乳头瘤病毒（HPV），因此患HPV相关癌症和癌前病变的风险更高。我们调查了FLG基因型与子宫颈、阴道、外阴、阴茎、肛门及头颈部HPV相关癌症以及子宫颈癌前病变发病率之间的关联。
我们纳入了来自丹麦哥本哈根同一背景人群中开展的四项基于人群研究的13376人。对参与者进行了欧洲人中最常见的FLG突变基因分型。直至2011年7月11日，癌症信息均取自丹麦癌症登记处。
共有489例HPV相关癌症和癌前病变的现患病例以及97例新发病例（中位随访时间11.5年）。FLG基因型与HPV相关癌症和癌前病变新发病例之间存在统计学显著关联，FLG突变携带者与野生型相比，风险比HR = 2.1（95%置信区间CI：1.2, 3.7）。
FLG功能丧失突变与HPV相关癌症和癌前病变的较高发病率相关，而这些疾病有可能通过筛查和疫苗进行预防。
