Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
Nutrients. 2022 Nov 1;14(21):4594. doi: 10.3390/nu14214594.
Paradoxically epidemiological data illustrate a negative relationship between dietary folate intake and colorectal cancer (CRC) risk. The occurrence and progression of CRC may be influenced by variants in some key enzyme coding genes in the folate metabolic pathway. We investigated the correlation between genetic variants in methionine synthase reductase () and methylenetetrahydrofolate reductase () and CRC survival.
This study used data collected from the Newfoundland Familial Colorectal Cancer Study. A total of 532 patients diagnosed with CRC for the first time from 1999 to 2003 were enrolled, and their mortality were tracked until April 2010. DNA samples were genotyped by Illumina's integrated quantum 1 million chip. Cox models were established to assess 33 tag single-nucleotide polymorphisms in and in relation to overall survival (OS), disease-free survival (DFS) and CRC-specific survival.
The and genes were associated with DFS and CRC-specific survival in CRC patients at the gene level. After multiple comparison adjustment, rs1801394 A (vs. G) allele was associated with increased DFS ( = 0.024), while rs3737966 (G vs. A), rs4846049 (T vs. G), rs1476413 (A vs. G), rs1801131 (C vs. A), rs12121543 (A vs. C), rs1801133 (C vs. T), rs4846052 (T vs. C), rs2066471 (A vs. G) and rs7533315 (T vs. C) were related to worse CRC-specific survival. Additionally, significant interactions were seen among pre-diagnostic alcohol consumption with rs1801394, rs3776467, rs326124, rs162040, and rs3776455, with superior OS associated with those protective variant alleles limited to patients with alcohol consumption under the median. The rs3737966 (G vs. A) allele seemed to be detrimental to CRC survival only among subjects with fruit intake below the median.
Polymorphic variants in and genes that code for key enzymes for folate metabolism may be associated with survival in patients with CRC. The gene-CRC outcome association seems modulated by alcohol drinking and fruit intake.
矛盾的是，流行病学数据表明，饮食叶酸摄入与结直肠癌（CRC）风险之间呈负相关。CRC 的发生和发展可能受到叶酸代谢途径中一些关键酶编码基因变异的影响。我们研究了甲硫氨酸合成酶还原酶（）和亚甲基四氢叶酸还原酶（）中的遗传变异与 CRC 生存之间的相关性。
本研究使用了 1999 年至 2003 年间首次诊断为 CRC 的 532 名患者的数据进行收集，并对其死亡率进行了跟踪，直到 2010 年 4 月。DNA 样本通过 Illumina 的集成量子百万芯片进行基因分型。建立 Cox 模型，以评估 33 个标签单核苷酸多态性与整体生存（OS）、无病生存（DFS）和 CRC 特异性生存的关系。
在 CRC 患者中，基因水平上与 DFS 和 CRC 特异性生存相关的基因是和。经过多次比较调整后，rs1801394A（与 G）等位基因与 DFS 增加相关（=0.024），而 rs3737966（G 与 A）、rs4846049（T 与 G）、rs1476413（A 与 G）、rs1801131（C 与 A）、rs12121543（A 与 C）、rs1801133（C 与 T）、rs4846052（T 与 C）、rs2066471（A 与 G）和 rs7533315（T 与 C）与 CRC 特异性生存较差相关。此外，还观察到预诊断饮酒与 rs1801394、rs3776467、rs326124、rs162040 和 rs3776455 之间存在显著的交互作用，那些与保护性变异等位基因相关的 OS 更好，仅限于饮酒中位数以下的患者。rs3737966（G 与 A）等位基因似乎仅在水果摄入量低于中位数的患者中对 CRC 生存有害。
叶酸代谢关键酶编码基因中的多态性变异可能与 CRC 患者的生存相关。基因-CRC 结局的关联似乎受到酒精摄入和水果摄入的调节。
