亚甲基四氢叶酸还原酶基因多态性与食管癌易感性的病例对照研究。

THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY.

机构信息

Universidade de São Paulo, Faculty of Medicine, Cancer Institute, University Hospital, Department of Gastroenterology - São Paulo (SP), Brazil.

出版信息

Arq Bras Cir Dig. 2022 Sep 9;35:e1684. doi: 10.1590/0102-672020220002e1684. eCollection 2022.

DOI:10.1590/0102-672020220002e1684

PMID:36102491

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9462861/

Abstract

BACKGROUND

The enzyme methylenetetrahydrofolate reductase is engaged in DNA synthesis through folate metabolism. Inhibiting the activity of this enzyme increases the susceptibility to mutations, and damage and aberrant DNA methylation, which alters the gene expression of tumor suppressors and proto-oncogenes, potential risk factors for esophageal cancer.

AIMS

This study aimed to investigate the association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and susceptibility to esophageal cancer, by assessing the distribution of genotypes and haplotypes between cases and controls, as well as to investigate the association of polymorphisms with clinical and epidemiological characteristics and survival.

METHODS

A total of 109 esophageal cancer patients who underwent esophagectomy were evaluated, while 102 subjects constitute the control group. Genomic DNA was isolated from the peripheral blood buffy coat followed by amplification by polymerase chain reaction and real-time analysis. Logistic regression was used to assess associations between polymorphisms and the risk of developing esophageal cancer.

RESULTS

There was no association for methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and haplotypes, with esophageal cancer susceptibility. Esophageal cancer patients carrying methylenetetrahydrofolate reductase 677TT polymorphism had higher risk of death from the disease. For polymorphic homozygote TT genotype, the risk of death significantly increased compared to wild-type genotype methylenetetrahydrofolate reductase 677CC (reference) cases (p=0.045; RR=2.22, 95%CI 1.02-4.83).

CONCLUSIONS

There was no association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and esophageal cancer susceptibility risk. Polymorphic homozygote genotype methylenetetrahydrofolate reductase 677TT was associated with higher risk of death after surgical treatment for esophageal cancer.

摘要

背景

酶亚甲基四氢叶酸还原酶通过叶酸代谢参与 DNA 合成。抑制该酶的活性会增加突变易感性、DNA 损伤和异常甲基化，从而改变肿瘤抑制基因和原癌基因的基因表达，这些都是食管癌的潜在危险因素。

目的

本研究旨在通过评估病例组和对照组之间基因型和单倍型的分布，探讨亚甲基四氢叶酸还原酶 677C>T 和亚甲基四氢叶酸还原酶 1298A>C 多态性与食管癌易感性的关系，并探讨多态性与临床和流行病学特征及生存的关系。

方法

共评估了 109 例接受食管切除术的食管癌患者，其中 102 例为对照组。从外周血白细胞层中分离基因组 DNA，然后通过聚合酶链反应和实时分析进行扩增。采用 logistic 回归评估多态性与患食管癌风险之间的关系。

结果

亚甲基四氢叶酸还原酶 677C>T 和亚甲基四氢叶酸还原酶 1298A>C 多态性及其单倍型与食管癌易感性无关。携带亚甲基四氢叶酸还原酶 677TT 多态性的食管癌患者死于该疾病的风险更高。与野生型亚甲基四氢叶酸还原酶 677CC 基因型（参照）相比，多态性纯合子 TT 基因型的死亡风险显著增加（p=0.045；RR=2.22，95%CI 1.02-4.83）。