对酒渣鼻在癌症风险中的作用的新认识：孟德尔随机化方法。

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

机构信息

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University Yubei Hospital (Yubei District People's Hospital of Chongqing), Chongqing, China.

出版信息

Skin Res Technol. 2024 May;30(5):e13737. doi: 10.1111/srt.13737.

DOI:10.1111/srt.13737

PMID:38769705

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11106556/

Abstract

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.

OBJECTIVES

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 (p = 0.71), cSCC (p = 0.45), BCC (p= 0.90), AK (p = 0.73), thyroid cancer (p = 0.59), glioma (p = 0.15), and hepatic cancer (p= 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; p = 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; p = 0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; p = 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.

摘要

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疾病，据报道与多种恶性肿瘤的风险增加有关，但因果关系的证据尚缺乏。

目的

系统评估酒渣鼻与几种癌症（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、神经胶质瘤和肝癌）之间的因果关系，并探讨潜在的发病机制。

方法

我们进行了一项双向两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来建立工具变量。通过多种方法评估因果关系，并通过敏感性分析评估结果的稳健性。

结果

酒渣鼻与 CMM（p=0.71）、cSCC（p=0.45）、BCC（p=0.90）、AK（p=0.73）、甲状腺癌（p=0.59）、神经胶质瘤（p=0.15）和肝癌（p=0.07）之间无显著因果关系的迹象，但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相关（比值比[OR]，1.10；95%置信区间[CI]，1.02-1.18；p=0.01）。TANK（TRAF 家族成员相关核因子 kappa B（NFKB）激活物）被确定为酒渣鼻（OR，0.90；95%CI，0.82-0.99；p=0.048）和 HER 阴性乳腺癌（OR，0.86；95%CI，0.75-0.98；p=0.032）的共同保护基因，主要富集于 NF-κB 信号转导的负调控，可能导致酒渣鼻与这种乳腺癌亚型之间的遗传联系。