在患有肿瘤的结直肠癌患者中，其肿瘤在p16（INK4a）、p4（ARF）和hMLH1呈现启动子高甲基化的情况下，特定微量营养素摄入量较低。

Lower specific micronutrient intake in colorectal cancer patients with tumors presenting promoter hypermethylation in p16(INK4a), p4(ARF) and hMLH1.

作者信息

Mas Sergi, Lafuente M Jose, Crescenti Anna, Trias Manuel, Ballesta Antonio, Molina Rafael, Zheng Shichun, Wiencke John K, Lafuente Amalia

机构信息

Department of Pharmacology, School of Medicine, IDIBAPS, University of Barcelona, Casanova 143, 08036 Barcelona, Spain.

出版信息

Anticancer Res. 2007 Mar-Apr;27(2):1151-6.

PMID:17465256

Abstract

BACKGROUND

The diversity of the Mediterranean diet and the heterogeneity of acquired epigenetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and promoter hypermethylation in genes implicated in the pathogenesis of these neoplasms (p16(INK4a), p14(ARF), hMLH1) and the interaction with methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism.

PATIENTS AND METHODS

For the molecular study, 120 CRC patients were analyzed for hMLH1 promoter methylation status and MTHFR genotyping. Dietary patterns and molecular data on p16(INK4a) and p14(ARF) methylation were obtained from previous studies with this populations.

RESULTS

Patients with methylation in p16(INK4a) consumed significantly less folate (p = 0.01), vitamin A (p = 0.01), vitamin B1 (p = 0.007), potassium (p = 0.03) and iron (p = 0.02) than controls. Patients with methylation in p14(ARF) or hMLH1 consumed significantly less vitamin A (p = 0.001 and p = 0.05, respectively).

CONCLUSION

These results support that certain micronutrients protect against colorectal neoplasia and emphasize the importance of considering the different molecular forms of CRC as etiologically distinct diseases.

摘要

背景

地中海饮食的多样性以及结直肠癌（CRC）中获得性表观遗传改变的异质性，促使我们研究饮食因素与这些肿瘤发病机制相关基因（p16(INK4a)、p14(ARF)、hMLH1）启动子高甲基化之间的可能关联，以及与亚甲基四氢叶酸还原酶（MTHFR）C677T多态性的相互作用。

患者与方法

对于分子研究，分析了120例CRC患者的hMLH1启动子甲基化状态和MTHFR基因分型。关于p16(INK4a)和p14(ARF)甲基化的饮食模式和分子数据来自此前对该人群的研究。

结果

与对照组相比，p16(INK4a)甲基化的患者叶酸（p = 0.01）、维生素A（p = 0.01）、维生素B1（p = 0.007）、钾（p = 0.03）和铁（p = 0.02）的摄入量显著较低。p14(ARF)或hMLH1甲基化的患者维生素A摄入量显著较低（分别为p = 0.001和p = 0.05）。