乳腺癌或卵巢癌的风险可以预测多早?向BRCA1和MGMT基因的表观遗传变化的传播

It is well known that mutations in the BRCA1 gene is implicated in breast and ovarian cancer and that these mutations can be inherited. This study examines is whether epigenetic changes to this gene, and the less understood MGMT gene, can be passed from mother to daughter.

全球妇女中这些癌症的乳腺癌和卵巢癌的发病率正在增加,2012年在全球范围内诊断出约170万例新病例。癌症率的增加带来了巨大的社会经济,情感和公共卫生的影响。成功治疗这些癌症的一个关键因素是早期检测和改善预防,这可以通过鉴定可以预测这些癌症易感性的生物标志物来帮助。因此,这将降低治疗成本以及死亡率和发病率。

已经是良好那个携带的女性BRCA1突变更有可能在50岁之前发展侵袭性乳腺肿瘤。作为肿瘤抑制基因,当BRCA1is unmutated or unaltered, it is actually protective against cancer (but when mutated, it can promote tumor growth). While mutation is one mechanism through whichBRCA1can become harmful, other mechanisms, such asDNA甲基化((which is essentially a mechanism acting as the on/off switch for many of our genes) can also deactivateBRCA1以及其他与癌症相关的基因导致癌症形成。

而突变BRCA1have been found to be responsible for the hereditary type of breast and ovarian cancers, to date there has been no evidence of inheritance for the methylatedBRCA1

Evidence of epigenetic inheritance from mother to daughter
在最近发表的一项研究中Clinical Epigenetics,我们检查了甲基化的发生率BRCA1genes in white blood cells of adult and newborn females. In addition, the study investigated the possible transmission of methylatedBRCA1从母亲到女儿。

A total of 865 females, including 290 mother-newborn pairs, were screened for the presence of methylatedBRCA1in their white blood cells. The results showed that the frequency of methylatedBRCA1成年和新生女性的相似之处(分别为9.3%和9.9%);表明甲基化BRCA1是从载体的早期生活中出现的。

In addition, we discovered that theMGMT基因是另一个与乳腺癌和卵巢癌发展有关的基因,也是白细胞中甲基化的。就像BRCA1,,,,whenMGMTis methylated, it poses more of a cancer threat to the carrier. Our results demonstrated that, similar to methylatedBRCA1,甲基化的频率MGMT成年女性和新生女性都相似(分别为13.1%和12.3%)。该结果表明甲基化MGMT从载体的早期生活中也出现。

What is exciting about our study is that it shows, for the first time, the transmission of methylatedBRCA1andMGMT从母亲到女儿。我们发现,在母纽伯恩对中,有20%和31%的母亲,携带甲基化的母亲BRCA1andMGMT分别有女儿,他们还测试了这些基因甲基化阳性。

另一方面,研究还发现,与未怀孕的女性相比,母亲的甲基化频率较低,妊娠可能会扭转这些基因的甲基化。我们假设怀孕期间这些基因的甲基化降低可能是预防乳腺癌的保护机制。但是,需要进一步的研究来验证这一点。

What risks do methylatedBRCA1orMGMT在白细胞中为女性带来?

为了理解pre的后果sence of methylatedBRCA1andMGMT健康女性白细胞中的基因,我们检查了这两个基因在乳腺癌和卵巢癌患者中的甲基化发生率。我们的结果证实了我们先前观察到的那些(在我们的研究中发表在BMC癌),,,,which is that 18% of breast cancer patients have methylatedBRCA1在其WBC中,15%的甲基化米克特。

卵巢癌是否观察到相同的模式?我们发现15%的卵巢癌患者甲基化BRCA1while 21% have methylatedMGMT。These results confirm that females who carry either methylatedBRCA1orMGMT乳腺癌和卵巢癌的风险更高。

意义和未来研究

这些基因的甲基化是从载体的早期生命中存在的事实,这表明它们可能用作生物标志物,以便早期发现易感乳腺癌和卵巢癌的雌性。这样的工具可以帮助预测(甚至可能预测)多达30%的乳腺癌和35%的卵巢癌病例。尽管需要更多的研究来开发可靠,准确的测试以识别这些表观遗传标记,但我们希望我们的研究为这种研究奠定了基础,并将为全球乳腺癌和卵巢癌的最终减少。

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