亚甲基四氢叶酸还原酶基因多态性与印度结直肠癌的关系。

Association of methylenetetrahydrofolate reductase gene polymorphisms & colorectal cancer in India.

机构信息

Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, India.

出版信息

Indian J Med Res. 2010 May;131:659-64.

PMID:20516537

Abstract

BACKGROUND & OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C-->T and 1298 A-->C have shown to impact several diseases including cancer. This case-control study was undertaken to analyse the association of the MTHFR gene polymorphisms 677 C-->T and 1298 A-->C and risk of colorectal cancer (CRC).

METHODS

One hundred patients with a confirmed histopathologic diagnosis of CRC and 86 age and gender matched controls with no history of cancer were taken for this study. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The risk association was estimated by compounding odds ratio (OR) with 95 per cent confidence interval (CI).

RESULTS

Genotype frequency of MTHFR 677 CC, CT and TT were 76.7, 22.1 and 1.16 per cent in controls, and 74, 25 and 1.0 per cent among patients. The 'T' allele frequency was 12.21 and 13.5 per cent in controls and patients respectively. The genotype frequency of MTHFR 1298 AA, AC, and CC were 25.6, 58.1 and 16.3 per cent for controls and 22, 70 and 8 per cent for patents respectively. The 'C' allele frequency for 1298 A-->C was 43.0 and 45.3 per cent respectively for controls and patients. The OR for 677 CT was 1.18 (95% CI 0.59-2.32, P = 0.642), OR for 1298 AC was 1.68 (95% CI 0.92-3.08, P = 0.092) and OR for 1298 CC was 0.45 (95% CI 0.18-1.12, P = 0.081). The OR for the combined heterozygous state (677 CT and 1298 AC) was 1.18 (95% CI 0.52-2.64, P =0.697).

INTERPRETATION & CONCLUSION: The frequency of the MTHFR 677 TT genotype is rare as compared to 1298 CC genotype in the population studied. There was no association between 677 C-->T and 1298 A-->C polymorphisms and risk of CRC either individually or in combination. The homozygous state for 1298 A-->C polymorphism appears to slightly lower risk of CRC. This needs to be confirmed with a larger sample size.

摘要

背景与目的

亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的关键酶，参与 DNA 合成、DNA 修复和 DNA 甲基化。MTHFR 的两个常见功能多态性 677C>T 和 1298A>C 已被证明与多种疾病有关，包括癌症。本病例对照研究旨在分析 MTHFR 基因多态性 677C>T 和 1298A>C 与结直肠癌（CRC）风险的关联。

方法

本研究纳入了 100 例经组织病理学证实的 CRC 患者和 86 例年龄和性别匹配、无癌症病史的对照者。从外周血样本中提取 DNA，采用 PCR-RFLP 法确定基因型。通过复合比值比（OR）及其 95%置信区间（CI）来估计风险关联。

结果

对照组中 MTHFR 677CC、CT 和 TT 的基因型频率分别为 76.7%、22.1%和 1.16%，患者组分别为 74%、25%和 1.0%。T 等位基因频率在对照组和患者组分别为 12.21%和 13.5%。对照组中 MTHFR 1298AA、AC 和 CC 的基因型频率分别为 25.6%、58.1%和 16.3%，患者组分别为 22%、70%和 8%。1298A>C 的 C 等位基因频率在对照组和患者组分别为 43.0%和 45.3%。677CT 的 OR 为 1.18（95%CI 0.59-2.32，P=0.642），1298AC 的 OR 为 1.68（95%CI 0.92-3.08，P=0.092），1298CC 的 OR 为 0.45（95%CI 0.18-1.12，P=0.081）。677CT 和 1298AC 杂合状态的 OR 为 1.18（95%CI 0.52-2.64，P=0.697）。