Singhal Saurabh, Kapoor Harit, Subramanian Saravanan, Agrawal Devendra K, Mittal Sumeet K
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 500, Phoenix, AZ, USA.
Clinical and Translational Sciences, Creighton University, 2500 California Plaza, Omaha, NE, USA.
J Gastrointest Cancer. 2019 Dec;50(4):867-878. doi: 10.1007/s12029-018-0164-6.
The vitamin D receptor (VDR) endocrine system has emerged as an endogenous pleiotropic biological cell regulator with anti-neoplastic effects on breast, colorectal, and prostatic adenocarcinomas. We studied the association of gene expression, polymorphisms of VDR, CYP27B1, and CYP24A1 genes and serum vitamin D levels as surrogate markers of disease progression in patients with acid reflux, Barrett's esophagus (BE), or esophageal adenocarcinoma (EAC).
We analyzed blood and tissue samples from patients with biopsy-confirmed BE or EAC for vitamin D levels, gene expressions, and polymorphisms in VDR (FokI [F/f], BsmI [B/b], ApaI [A/a], and TaqI [T/t]), CYP27B1 (HinfI [H/h]), and CYP24A1 (Hpy1881 [Y/y]). Percentages of homozygous dominant/recessive or heterozygous traits were assessed for each polymorphism in all patient subgroups.
Genomic Bb and FF polymorphisms were highly prevalent in EAC patients, whereas BE patients had a high prevalence of wild-type Hpy1881 (YY polymorphism). Some polymorphisms (Yy for CYP24A1, bb for VDR) were noted only in EAC patients. Yy and bb forms were both uniquely present in some EAC patients without associated Barrett's lesions, but not in patients with concomitant BE. AA and bb polymorphisms were associated with decreased response to neoadjuvant therapy. A high level of VDR and CYP24A1 mRNA expression was observed in EAC tissue of non-responders. Serum vitamin D deficiency was common in EAC patients.
Specific polymorphisms in vitamin D metabolism-related genes are associated with the likelihood of reflux-BE-EAC progression. Identifying such polymorphisms may aid in development of better surveillance and diagnostic and therapeutic protocols.
维生素D受体（VDR）内分泌系统已成为一种内源性多效生物细胞调节剂，对乳腺癌、结直肠癌和前列腺腺癌具有抗肿瘤作用。我们研究了VDR、CYP27B1和CYP24A1基因的基因表达、多态性以及血清维生素D水平之间的关联，将其作为胃食管反流病、巴雷特食管（BE）或食管腺癌（EAC）患者疾病进展的替代标志物。
我们分析了经活检确诊为BE或EAC患者的血液和组织样本，检测维生素D水平、基因表达以及VDR（FokI [F/f]、BsmI [B/b]、ApaI [A/a]和TaqI [T/t]）、CYP27B1（HinfI [H/h]）和CYP24A1（Hpy1881 [Y/y]）的多态性。评估所有患者亚组中每种多态性的纯合显性/隐性或杂合性状的百分比。
基因组Bb和FF多态性在EAC患者中高度普遍，而BE患者野生型Hpy1881（YY多态性）的患病率较高。一些多态性（CYP24A1的Yy、VDR的bb）仅在EAC患者中出现。Yy和bb形式仅在一些无相关巴雷特病变的EAC患者中独特存在，而在伴有BE的患者中不存在。AA和bb多态性与新辅助治疗反应降低有关。在无反应者的EAC组织中观察到高水平的VDR和CYP24A1 mRNA表达。EAC患者中血清维生素D缺乏很常见。
维生素D代谢相关基因的特定多态性与反流 - BE - EAC进展的可能性相关。识别此类多态性可能有助于制定更好的监测、诊断和治疗方案。
