Jakubowska Anna, Gronwald Jacek, Menkiszak Janusz, Górski Bohdan, Huzarski Tomasz, Byrski Tomasz, Edler Lutz, Lubiński Jan, Scott Rodney J, Hamann Ute
Pomeranian Medical University, ul Polabska 4, 70-111, Szczecin, Poland.
Breast Cancer Res Treat. 2007 Sep;104(3):299-308. doi: 10.1007/s10549-006-9417-3. Epub 2006 Oct 25.
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 Polish BRCA1 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.
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的关键调节酶，据怀疑它通过对DNA甲基化和核苷酸合成的影响在癌症病因学中发挥作用。在本研究中，我们调查了MTHFR基因的两种功能多态性，即MTHFR_677_C>T和MTHFR_1298_A>C，对波兰BRCA1突变携带者患乳腺癌和卵巢癌风险的影响。该研究纳入了319例乳腺癌病例、146例卵巢癌病例以及290例未患乳腺癌、卵巢癌、原位乳腺癌或任何其他类型癌症的对照。使用聚合酶链反应随后进行限制性片段长度多态性分析进行基因分型分析。考虑到一系列可能使任何关联产生偏差的混杂变量，采用单变量和多变量逻辑回归计算优势比（OR）。结果显示，MTHFR_677_C>T变化与乳腺癌和卵巢癌风险增加相关。MTHFR_1298_A>C多态性仅与乳腺癌风险降低相关。总体而言，MTHFR基因中的功能多态性似乎会改变乳腺癌风险，并且可能会改变具有遗传易感性女性患卵巢癌的风险。
