Risk of colorectal cancer associated with the C677T polymorphism in 5, 10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients
Risk of colorectal cancer associated with the C677T polymorphism in 5, 10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients
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DOI：
10.3945/ajcn.2008.25877
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发表时间：
2008-11-01
影响因子：
7.1
通讯作者：
Cravo, Marilia
中科院分区：
文献类型：
--
作者：
Guerreiro, Catarina Sousa;Carmona, Bruno;Cravo, Marilia
背景资料：叶酸代谢相关基因和某些甲基化相关营养素基因的多态性与结直肠癌（CRC）的发生有关。目的：探讨3种基因多态性[C677 T MTHFR（亚甲基四氢叶酸还原酶），A2756 G MTR（甲硫氨酸合酶）和C1420 T SHMT（丝氨酸羟甲基转移酶）]与CRC风险中甲基供体营养素的摄入。设计：对年龄和性别匹配的CRC患者（n = 196）和健康对照组（n = 200）的甲基供体营养素摄入量和3种多态性进行了评估。除叶酸摄入量显著低于患者（P = 0.02）外，两组间其他甲基供体营养素的饮食摄入量无差异。高叶酸摄入量（> 406.7 μ g/d）与CRC风险显著降低相关（比值比：0.67; 95%CI：0.45，0.99）。A2756 G MTR多态性与结直肠癌的发生风险无关。相比之下，C677 T MTHFR变体（TT）的纯合性使CRC风险增加3.0倍（95% CI：1.3，6.7）。类似地，C1420 T SHMT多态性的纯合性也使发生CRC的风险增加2.6倍（95%CI：1.1，5.9）。当研究变量之间的相互作用时，所有甲基供体营养素的低摄入量与C677 T MTHFR多态性纯合子参与者的CRC风险增加相关，但仅观察到叶酸的统计学显著相互作用（比值比：14.0; 95%CI：1.8，108.5）。MTR或SHMT polymorphis.Conclusion：这些结果显示C677 T MTHFR变异与不同叶酸摄入量对结直肠癌风险之间存在关联。Am J Clin Nutr 2008; 88：1413-8。
Background: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC).Objective: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk.Design: Patients withCRC(n = 196) and healthy controls (n = 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms.Results: Except for folate intake, which was significantly lower in patients (P = 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate (> 406.7 mu g/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677T MTHFR variant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk of CRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms.Conclusion: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC. Am J Clin Nutr 2008; 88: 1413-8.