Association of Vitamin D Receptor Gene Polymorphisms With Melanoma Risk: A Meta-analysis and Systematic Review.
- 作者列表："Birke M","Schöpe J","Wagenpfeil S","Vogt T","Reichrath J
BACKGROUND/AIM:Increasing evidence indicates a relevance of the vitamin D endocrine system for pathogenesis of malignant melanoma. We performed a systematic review and meta-analysis to update previous reports that investigated the association between vitamin D receptor (VDR) gene polymorphisms and melanoma risk. MATERIALS AND METHODS:A comprehensive literature search (PubMed, ISI Web of Science) identified a total of 14 studies that were eligible for inclusion in our meta-analysis. In the statistical analysis, the ORs and the 95% CIs were calculated for the dominant and recessive models for seven VDR gene polymorphisms, namely rs2228570 (FokI), rs731236 (TaqI), rs1544410 (BsmI), rs4516035 (A-1012G), rs11568820 (Cdx2), rs7975232 (ApaI) and rs739837 (BglI). Results were illustrated in Forest Plots. Publication bias was tested using Funnel Plots and the Egger's test. RESULTS:Our meta-analysis showed in the dominant model (Bb + BB vs. bb) a significant association of a 15% risk reduction in malignant melanoma incidence for carriers of the rarer allele B of rs1544410 (Bsml). Notably, the dominant model (Ff + ff vs. FF) of rs2228570 (FokI) demonstrates that carriers of the rarer allele f are 22% more likely to develop malignant melanoma. For rs7975232 (ApaI), there is a 20% higher risk of melanoma for carriers of the rarer a allele (Aa + aa vs. AA). The results of the meta-analysis revealed no significant association between melanoma risk and the other investigated VDR polymorphisms. CONCLUSION:The VDR variants FokI, ApaI and BsmI may influence the susceptibility to developing melanoma. These findings support the concept, that the vitamin D endocrine system is of importance for pathogenesis of malignant melanoma.
背景/目的: 越来越多的证据表明维生素d内分泌系统与恶性黑色素瘤的发病机制相关。我们进行了系统综述和荟萃分析，以更新以前研究维生素D受体 (VDR) 基因多态性与黑色素瘤风险之间相关性的报告。 材料和方法: 全面的文献检索 (PubMed，ISI Web of Science) 共确定了 14 项符合纳入我们荟萃分析的研究。在统计分析中，计算了 7 个VDR基因多态性的显性和隐性模型的ORs和 95% ci，即rs2228570 (FokI) 、rs731236 (TaqI) 、rs1544410 (BsmI) 、rs4516035 (A-1012G) 、rs11568820 (Cdx2) 、rs7975232 (ApaI) 和rs739837 (BglI)。结果在森林地块中说明。使用漏斗图和Egger 's检验测试发表偏倚。 结果: 我们的荟萃分析显示在主导模型 (Bb + BB vs. bb) rs1544410 (Bsml) 罕见等位基因B携带者恶性黑色素瘤发病率降低 15% 的显著相关性。值得注意的是，rs2228570 (FokI) 的显性模型 (Ff + ff vs. FF) 证明，更罕见等位基因f的携带者发生恶性黑色素瘤的可能性增加 22%。对于rs7975232 (ApaI)，更罕见的a等位基因 (Aa + aa vs. AA) 携带者患黑色素瘤的风险高 20%。荟萃分析的结果显示黑色素瘤风险与其他研究的VDR多态性之间无显著相关性。 结论: VDR变异体FokI、ApaI和BsmI可能影响黑色素瘤的易感性。这些发现支持维生素d内分泌系统在恶性黑色素瘤发病机制中的重要性这一概念。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.