Association of MTHFR, MTR, MTRR, RFC1, and DHFR Gene Polymorphisms with Susceptibility to Sporadic Colon Cancer
Association of MTHFR, MTR, MTRR, RFC1, and DHFR Gene Polymorphisms with Susceptibility to Sporadic Colon Cancer
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DOI：
10.1089/dna.2010.1189
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发表时间：
2011-10-01
影响因子：
3.1
通讯作者：
Kapitanovic, Sanja
中科院分区：
文献类型：
--
作者：
Jokic, Mladen;Brcic-Kostic, Krunoslav;Kapitanovic, Sanja
叶酸水平的改变可能在结肠癌的发生中起重要作用。本研究的目的是研究关键叶酸代谢基因多态性与散发性结肠癌易感性的关系。对来自克罗地亚的300名健康受试者和300名结肠癌患者进行了6种常见多态性（MTHFR基因2种，MTR、MTRR、RFC1和DHFR基因各1种）的基因分型。结果提示MTRR 66 AA对散发性结肠癌可能具有保护作用（OR = 0.655; 95% CI = 0.441-0.973; p = 0.04）。单倍型的最大似然分析显示，在对照组和患者组中，MTHFR基因的两种多态性（C677T和A1298C）之间存在连锁不平衡（LD） （p < 0.01）。MTRR A66G和MTHFR A1298C多态性之间也存在LD，但仅在一组患者中存在（p < 0.01）。A66G和A1298C多态性的单倍型A/A被证明具有保护作用（OR = 0.775; 95% CI = 0.603-0.996; p = 0.04），而单倍型A/G是结肠癌的危险因素（OR = 1.270; 95% CI = 1.007-1.602; p = 0.04）。与之前的一些研究相反，单位点分析没有发现与结肠癌风险相关的多态性，但表明MTRR 66 AA基因型可能具有保护作用。位于不同染色体上的两个基因座（MTHFR A1298C和MTRR A66G）之间检测到显著的LD，表明它们的连锁维持机制具有很强的选择力。这两种多态性的等位基因的特定组合对结肠癌的易感性有保护作用，但也有风险作用。
Altered folate levels may play an important role in colon carcinogenesis. The aim of this study was to investigate the association of polymorphisms in key folate-metabolizing genes with susceptibility to sporadic colon cancer. Six common polymorphisms (two in MTHFR and one each in MTR, MTRR, RFC1, and DHFR genes) were genotyped in 300 healthy subjects and 300 colon cancer patients from Croatia. Obtained results indicate possible protective role of MTRR 66 AA in sporadic colon cancer (OR = 0.655; 95% CI = 0.441-0.973; p = 0.04). Maximum-likelihood analysis of haplotypes revealed a linkage disequilibrium (LD) between the two investigated polymorphisms of the MTHFR gene (C677T and A1298C), both in the control and patient groups (p < 0.01 for both). LD was also detected between MTRR A66G and MTHFR A1298C polymorphisms but only in a group of patients (p < 0.01). A haplotype of A66G and A1298C polymorphisms, A/A, proved to be protective (OR = 0.775; 95% CI = 0.603-0.996; p = 0.04), whereas haplotype A/G was a risk factor for colon cancer (OR = 1.270; 95% CI = 1.007-1.602; p = 0.04). Contrary to some previous studies, single-locus analyses identified no polymorphisms associated with risk for colon cancer, but demonstrated a possible protective effect of MTRR 66 AA genotype. The detected significant LD between two loci (MTHFR A1298C and MTRR A66G) located on different chromosomes indicates a strong selective force as a mechanism for the maintenance of their linkage. Specific combinations of alleles of these two polymorphisms showed a protective but also a risk effect on colon cancer susceptibility.