Guerreiro Catarina Sousa, Carmona Bruno, Gonçalves Susana, Carolino Elisabete, Fidalgo Paulo, Brito Miguel, Leitão Carlos Nobre, Cravo Marília
Escola Superior de Tecnologia da Saúde de Lisboa, Unidade de Nutrição e Metabolismo do Instituto de Medicina Molecular da Universidade de Lisboa, Lisboa, Portugal.
Am J Clin Nutr. 2008 Nov;88(5):1413-8. doi: 10.3945/ajcn.2008.25877.
Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC).
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.
Patients with CRC (n = 196) and healthy controls (n = 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms.
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 microg/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.
These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.
参与叶酸及一些甲基相关营养素代谢的基因中的多态性与结直肠癌（CRC）有关。
我们评估了3种基因多态性[C677T亚甲基四氢叶酸还原酶（MTHFR）、A2756G甲硫氨酸合成酶（MTR）和C1420T丝氨酸羟甲基转移酶（SHMT）]与甲基供体营养素摄入在结直肠癌风险中的关联。
对年龄和性别匹配的结直肠癌患者（n = 196）和健康对照者（n = 200）进行甲基供体营养素摄入及这3种多态性的评估。
除患者的叶酸摄入量显著较低（P = 0.02）外，两组间其他甲基供体营养素的饮食摄入量未观察到差异。高叶酸摄入量（>406.7微克/天）与结直肠癌风险显著降低相关（比值比：0.67；95%可信区间：0.45，0.99）。A2756G MTR多态性与患结直肠癌的风险无关。相反，C677T MTHFR变体纯合子（TT）患结直肠癌的风险增加3.0倍（95%可信区间：1.3，6.7）。同样，C1420T SHMT多态性纯合子患结直肠癌的风险也增加2.6倍（95%可信区间：1.1，5.9）。在研究变量之间的相互作用时，对于C677T MTHFR多态性的纯合参与者，所有甲基供体营养素的低摄入量与结直肠癌风险增加相关，但仅在叶酸方面观察到具有统计学意义的相互作用（比值比：14.0；95%可信区间：1.8，108.5）。MTR或SHMT多态性未观察到显著关联。
这些结果表明C677T MTHFR变体与不同叶酸摄入量在结直肠癌风险方面存在关联。
