De Re Valli, Cannizzaro R, Canzonieri V, Cecchin E, Caggiari L, De Mattia E, Pratesi C, De Paoli P, Toffoli G
Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Aviano, Italy.
Tumour Biol. 2010 Jan;31(1):23-32. doi: 10.1007/s13277-009-0004-1. Epub 2009 Dec 18.
Two common mutations, 677 C-->T and a1298 A-->C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex-age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677-1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population.
亚甲基四氢叶酸还原酶基因（MTHFR）中的两种常见突变，即677C→T和a1298A→C，会降低MTHFR的活性以及叶酸代谢。在相当比例的胃癌（GC）病例中存在家族聚集现象，这表明遗传易感性在确定风险方面具有重要意义。在本研究中，我们评估了57例确诊为GC的患者、37例有一级亲属患GC病史的患者（GC亲属）以及454名献血者的MTHFR基因多态性。同时也确定了幽门螺杆菌（HP）感染情况。相对于献血者，GC患者中677TT的风险增加（优势比（OR）=1.98），当我们比较性别年龄匹配的GC患者和献血者时，统计学意义依然存在（OR = 2.37）。在女性中发现677TT基因型与GC有关联（OR = 3.10），而在两性中667C等位基因频率均降低。当按性别和年龄对677 - 1298基因型进行分层时，未检测到统计学上的显著关联。GC亲属中的男性显示出比献血者更高的1298C等位基因频率（OR = 4.38）。在GC患者和GC亲属之间，HP感染频率相似。总之，总体研究结果支持叶酸在GC风险中起作用这一假说。GC亲属中677TT的频率与普通人群相似。
