Common filaggrin gene loss-of-function variants are associated with skin cancer risk

Adelanwa, Ayodele; Yousaf, Ahmed; Wei, Fang; Kolodney, Michael S.

doi:10.1016/j.jaad.2021.09.068

Cited by 1 publication

(4 citation statements)

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“…Several retrospective studies have showed that patients with FLG loss-of-function (LOF) mutations have increased risk of melanoma and cSCC. 4,36,37 Additionally, the chronic inflammatory stimulation may also contribute to the development of cancer. 38 Persistent chronic inflammation drives the transformation of cells of cancer origin by signalling to immune cells and tumour cells and producing reactive nitrogen intermediates (RNI) and reactive oxygen species (ROS) that lead to DNA damage and genomic instability.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, FLG mutations may lead to an increased susceptibility to UV radiation and a higher risk of skin cancer. Several retrospective studies have showed that patients with FLG loss‐of‐function (LOF) mutations have increased risk of melanoma and cSCC 4,36,37 . Additionally, the chronic inflammatory stimulation may also contribute to the development of cancer 38 .…”

Section: Discussionmentioning

confidence: 99%

“…2 Skin barrier dysfunction is primarily due to mutations in the filaggrin gene, which may enhance transcutaneous penetration of exogenous molecules and increased UV-induced damage. 3,4 Cell-mediated immune dysregulation may alter the immune response to cancer in patients with AD. Severe cases often require systemic immunosuppressive therapy, which may be associated with an increased risk of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…The pathogenesis of AD is complex and involves aberrant immune function, impaired skin barrier and environmental triggers of skin inflammation 2 . Skin barrier dysfunction is primarily due to mutations in the filaggrin gene, which may enhance transcutaneous penetration of exogenous molecules and increased UV‐induced damage 3,4 . Cell‐mediated immune dysregulation may alter the immune response to cancer in patients with AD.…”

Section: Introductionmentioning

confidence: 99%

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The causal effects of atopic dermatitis on the risk of skin cancers: A two‐sample Mendelian randomization study

Luo,

Zheng,

Zhuo

et al. 2023

Acad Dermatol Venereol

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BackgroundObservational and epidemiological studies show conflicting results on the relationship between atopic dermatitis and skin cancer. Additionally, observational studies are susceptible to the reverse causation and confounders, thus, may not interpret true causal relationships. The causal effects of atopic dermatitis on the risk of skin cancers remains unclear.ObjectivesTo investigate the causal relationship between atopic dermatitis and skin cancer including cutaneous malignant melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma and actinic keratosis.MethodsWe performed a two‐sample Mendelian randomization analysis based on summary datasets of public genome‐wide association studies of European ancestry. The inverse variance‐weighted approach was applied as the main analysis. MR–Egger and weighted median methods were used to complement the inverse variance‐weighted results. A series of sensitivity analyses were used to ensure the robustness of the causality estimates.ResultsInverse variance‐weighted method showed that genetically predicted dermatitis patients were significantly associated with an increased incidence of basal cell carcinoma (OR, 1.20; 95% CI, 1.10–1.31; p = 4.07E‐05) and cutaneous squamous cell carcinoma (OR, 1.14; 95% CI, 1.10–1.19; p = 1.05E‐11). However, we did not find a significant causality for atopic dermatitis on melanoma neither did we find actinic keratosis. Subsequent sensitive analyses supported these results.ConclusionsOur study identified the causality between atopic dermatitis basal cell carcinoma and squamous cell carcinoma. Accordingly, regular skin cancer screening is recommended for patients with atopic dermatitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%