背景:慢性炎症已被证明可促进癌症进展。酒渣鼻确实是一种长期的炎症性皮肤病,据报道与几种恶性肿瘤的风险增加有关。但是缺乏因果关系的证据。
目的:为了系统地估计酒渣鼻与几种癌症之间的因果关系,包括皮肤恶性黑色素瘤(CMM),皮肤鳞状细胞癌(cSCC),基底细胞癌(BCC),光化性角化病(AK),甲状腺癌,乳腺癌,胶质瘤和肝癌,以及探索潜在的潜在发病机制。
方法:我们进行了一项双向双样本孟德尔随机化研究,以探讨酒渣鼻与几种癌症之间的潜在因果关系。使用与酒渣鼻和癌症相关的全基因组显著单核苷酸多态性建立仪器变量。因果关系的评估是通过多种方法进行的,并通过敏感性分析评估结果的稳健性。
结果:没有明显的迹象表明酒渣鼻对CMM的因果关系(pivw=0.71),cSCC(枢轴=0.45),BCC(枢轴=0.90),AK(pivw=0.73),甲状腺癌(pivw=0.59),胶质瘤(枢轴=0.15),和肝癌(pivw=0.07),但是酒渣鼻的遗传风险与人类表皮生长因子受体(HER)阴性乳腺癌的易感性增加有关(优势比[OR],1.10;95%置信区间[CI],1.02-1.18;枢轴=0.01)。TANK(TRAF家族成员相关的核因子κB(NFKB)激活剂)被鉴定为两种酒渣鼻的共同保护基因(OR,0.90;95%CI,0.82-0.99;pivw=0.048)和HER阴性乳腺恶性肿瘤(OR,0.86;95%CI,0.75-0.98;枢轴=0.032),主要富含NF-κB信号转导的负调节,可能有助于酒渣鼻与乳腺癌这种亚型之间的遗传联系。
结论:我们的研究结果为酒渣鼻和HER阴性的乳腺恶性肿瘤风险之间的因果关系提供了暗示性证据。
BACKGROUND: Chronic 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.
OBJECTIVE: To 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.
METHODS: We 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.
RESULTS: There 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-κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer.
CONCLUSIONS: Our findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk.