Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks
Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks
复制标题
DOI：
10.1007/s10549-006-9417-3
复制
发表时间：
2007-09-01
影响因子：
3.8
通讯作者：
Hamann, Ute
中科院分区：
文献类型：
--
作者：
Jakubowska, Anna;Gronwald, Jacek;Hamann, Ute
亚甲基四氢叶酸还原酶(MTHFR)是叶酸代谢的关键调节酶，通过影响DNA甲基化和核苷酸合成，在癌症的发病机制中发挥重要作用。在这项研究中，我们研究了MTHFR基因的两个功能多态性MTHFR_677_C>；T和MTHFR_1298_A>；C对PolishBRCA1突变携带者患乳腺癌和卵巢癌风险的影响。这项研究包括319例乳腺癌病例，146例卵巢癌病例和290名对照，未受乳腺癌和卵巢癌、原位乳腺癌或任何其他类型癌症的影响。采用聚合酶链式反应和限制性片段长度多态性分析进行基因分型。使用单变量和多变量Logistic回归计算优势比(OR)，同时考虑了一系列可能会偏向任何关联的混杂变量。结果显示，MTHFR_677_C和GT；T的改变与乳腺癌和卵巢癌的风险增加有关。MTHFR_1298_A和GT；C基因多态只与乳腺癌风险降低相关。总之，MTHFR基因的功能多态似乎改变了乳腺癌的风险，并可能潜在地改变具有遗传易感性的女性患卵巢癌的风险。
Methylenetetrahydrofolate reductase ( MTHFR), a key regulatory enzyme in the metabolism of folate, is suspected to play a role in the etiology of cancer, via its effects on DNA methylation and nucleotide synthesis. In this study we have investigated the effect of two functional polymorphisms of the MTHFR gene, MTHFR_ 677_ C > T and MTHFR_ 1298_ A > C, on breast and ovarian cancer risk in PolishBRCA1 mutation carriers. The study included 319 breast cancer cases, 146 ovarian cancer cases and 290 controls unaffected by breast and ovarian cancer, in situ breast cancer or any other kind of cancer. Genotyping analysis was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using univariate and multivariate logistic regression taking into account a series of confounding variables that potentially could have biased any association. The results revealed that the MTHFR _ 677_ C > T change was associated with an increased risk of breast and ovarian cancer. The MTHFR_ 1298_ A > C polymorphism was only associated with a decrease in breast cancer risk. Together, it appears that functional polymorphisms in the MTHFR gene modify the risk of breast and may potentially alter the risk of ovarian cancer in women with an inherited predisposition.