MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients.
MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients.
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DOI：
10.1016/j.cancergencyto.2009.11.014
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发表时间：
2010-03
影响因子：
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通讯作者：
Abdollahi K
中科院分区：
文献类型：
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作者：
Naghibalhossaini F;Mokarram P;Khalili I;Vasei M;Hosseini SV;Ashktorab H;Rasti M;Abdollahi K
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢途径中的关键酶。我们的目的是检验MTHFR的C677 T和A1298 C变异体易患微卫星不稳定（MSI）结直肠癌的假设。我们确定了伊朗南部设拉子175名散发性结直肠癌患者和总共231名正常对照的MTHFR基因型。在我们的样本中发现的基因型中，MTHFR CT和CT + TT与CRC发病风险增加相关[比值比（OR）= 2.4，95%置信区间（95%CI）= 1.8-4.4; OR = 2.4，95%CI = 1.6-3.6]。双杂合子677 CT/1298 AC和双纯合子677 TT/1298 AA和677 CC/1298 CC基因型也显示与对照组的野生型677 CC/1298 AA基因型相比发生CRC的风险显著增加。151例肿瘤中MSI阳性36例（23.8%）。MSI在近端肿瘤（OR = 10.4; 95%CI = 3.9-27.8）和吸烟者（OR = 2.9; 95%CI = 1.3-6.7）中更常见。在病例对照比较中，MTHFR 677 CT + TT基因型与MSI密切相关（OR = 2.6; 95%CI = 1.3-5.3）。错配修复基因的高甲基化与MSI的发生率呈正相关（P = 0.00）。我们的数据表明MTHFR 677 CT + TT变异基因型可能是MSI+癌症的危险因素。
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway. We aimed to test the hypothesis that C677T and A1298C variants of MTHFR predispose to microsatellite instable (MSI) colorectal cancer. We determined MTHFR genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in Shiraz, Southern Iran. Among the genotypes found in our samples, MTHFR CT and CT + TT were associated with increased risk for CRC incidence [odds ratio (OR) = 2.4, 95% confidence interval (95%CI) = 1.8–4.4; OR = 2.4, 95%CI = 1.6–3.6, respectively]. Double heterozygotes 677CT/1298AC and double homozygote 677TT/1298AA and 677CC/1298CC genotypes also showed a significantly increased risk of developing CRC compared with the wild-type 677CC/1298AA genotypes of the controls. Among the 151 tumors tested, 36 (23.8%) were MSI+. MSI was more common in proximal tumors (OR = 10.4; 95%CI = 3.9–27.8) and in smokers (OR = 2.9; 95%CI = 1.3–6.7). In a case–control comparison, the MTHFR 677CT + TT genotype was strongly associated with MSI (OR = 2.6; 95%CI = 1.3–5.3). Hypermethylation of mismatch repair genes was positively related with MSI incidence in these tumor series (P = 0.00). Our data suggest that the MTHFR 677CT + TT variant genotype may be a risk factor for MSI+ cancer.