Matakidou A, El Galta R, Rudd M F, Webb E L, Bridle H, Eisen T, Houlston R S
Section of Cancer Genetics, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey SM2 5NG, UK.
Br J Cancer. 2007 Jul 16;97(2):247-52. doi: 10.1038/sj.bjc.6603830. Epub 2007 May 29.
Functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) of folate metabolism genes can influence the methylation of tumour suppressor genes, thereby potentially impacting on tumour behaviour. To investigate whether such polymorphisms influence lung cancer survival, we genotyped 14 nsSNPs mapping to methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2), methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non-small cell (NSCLC) and 154 with small cell lung cancer (SCLC). The most significant association detected was with MTHFS Thr202Ala, with carriers of variant alleles having a worse prognosis (hazard ratio (HR)=1.49; 95% confidence interval: 1.14-1.94). Associations were also detected between overall survival (OS) in SCLC and homozygosity for MTHFR 222Val (HR=1.92; 1.03-3.58) and between OS from NSCLC and MTRR 175Leu carrier status (HR=1.36; 1.06-1.75). While there is evidence that variation in the folate metabolism genes may influence prognosis from lung cancer, current data are insufficiently robust to distinguish individual patient outcome.
叶酸代谢基因的功能性非同义单核苷酸多态性（nsSNPs）可影响肿瘤抑制基因的甲基化，从而可能影响肿瘤行为。为了研究此类多态性是否会影响肺癌患者的生存率，我们对619例初发疾病的白种女性进行了基因分型，其中465例为非小细胞肺癌（NSCLC），154例为小细胞肺癌（SCLC），检测了14个位于亚甲基四氢叶酸还原酶（MTHFR）、甲硫氨酸合成酶（MTR）、甲硫氨酸合成酶还原酶（MTRR）、DNA甲基转移酶（DNMT2）、亚甲基四氢叶酸脱氢酶（MTHFD1）和亚胺甲基四氢叶酸合成酶（MTHFS）基因上的nsSNPs。检测到的最显著关联是与MTHFS基因的Thr202Ala多态性，携带变异等位基因的患者预后较差（风险比（HR）=1.49；95%置信区间：1.14 - 1.94）。在SCLC患者的总生存期（OS）与MTHFR基因222Val纯合性之间（HR = 1.92；1.03 - 3.58）以及NSCLC患者的OS与MTRR基因175Leu携带者状态之间（HR = 1.36；1.06 - 1.75）也检测到了关联。虽然有证据表明叶酸代谢基因的变异可能影响肺癌患者的预后，但目前的数据不够充分，无法区分个体患者的预后情况。
