Novel insights into rosacea's role in cancer risk: A Mendelian randomization approach

作者全名：Luo, Mao; Wei, Bin

作者地址：[Luo, Mao; Wei, Bin] Chongqing Med Univ, Affiliated Hosp 1, Dept Dermatol, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Luo, Mao] Chongqing Med Univ, Affiliated Hosp 1, Yubei Hosp, Yubei Dist Peoples Hosp Chongqing,Dept Dermatol, Chongqing, Peoples R China

通信作者：Wei, B (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Dermatol, 1 Youyi Rd, Chongqing 400016, Peoples R China.

来源：SKIN RESEARCH AND TECHNOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001227475400001

JCR分区：Q3

影响因子：2

年份：2024

卷号：30

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：actinic keratosis; basal cell carcinoma; breast cancer; carcinoma; cutaneous malignant melanoma; cutaneous squamous cell carcinoma; glioma; hepatic cancer; mendelian randomization; rosacea; thyroid cancer

摘要：BackgroundChronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long-term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking.ObjectivesTo systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis.MethodsWe conducted a bidirectional two-sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome-wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses.ResultsThere was no significant indication of causal effects of rosacea on CMM (pivw = 0.71), cSCC (pivw = 0.45), BCC (pivw = 0.90), AK (pivw = 0.73), thyroid cancer (pivw = 0.59), glioma (pivw = 0.15), and hepatic cancer (pivw = 0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)-negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18; pivw = 0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82-0.99; pivw = 0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; pivw = 0.032), which was primarily enriched in the negative regulation of NF-kappa B signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer.ConclusionsOur findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk.

基金机构：Chongqing science and health joint medical scientific research [2024MSXM069]; Chongqing science and health joint medical scientific research project [2023NSCQ-MSX0372]; Chongqing natural science foundation project

基金资助正文：The data used for this MR analysis were extracted from the FinnGen consortium and IEU Open GWAS project. The authors thank all investigators for sharing these data. This work was supported by Chongqing science and health joint medical scientific research project (2024MSXM069) and Chongqing natural science foundation project (2023NSCQ-MSX0372).