Pregnancy Estrogens, Diet, and Breast Cancer Risk

雌激素水平在怀孕期间升高50-100倍，怀孕雌激素水平的个体间变异性为4-6倍。 显示最高妊娠雌激素水平的妇女被认为是在一个显着增加的风险发展为乳腺癌，可能是由于雌激素诱导的促进现有的转化细胞。 饮食，特别是膳食脂肪，可能会影响怀孕雌激素水平和以后的乳腺癌风险。 在我们的动物研究中，高脂肪摄入量显着增加妊娠雌激素水平和增加妊娠促进乳腺肿瘤的发病率。 代谢雌激素的基因多态性与乳腺癌风险增加有关，也可能影响怀孕雌激素水平。我们的研究有两个主要目的：（1）研究膳食脂肪摄入是否会影响女性的妊娠雌激素水平，可能是通过与CYP 17和COMT的多态性相互作用，（2）研究最高的妊娠雌激素水平是否会通过增加生长因子水平来增加乳腺癌的风险。这些生长因子可能来源于突变或已经转化的乳腺细胞，这些细胞在怀孕期间受到高雌激素水平的刺激。 将测量乳头抽吸液（NAF）中的生长因子水平，NAF可使用吸奶器从非哺乳期乳房中获得。 因此，将检验以下假设：假设1。 我们假设高脂肪摄入和体重增加会增加妊娠雌激素水平。 我们进一步假设CYP 17或COMT的多态性影响这些相互作用。假设2。 我们推测，妊娠期间较高的循环雌二醇水平与乳头抽吸液中生长因子水平升高相关，包括EGF、TGF α和IGF-1/IGF结合蛋白3。 这些目标将在200名孕妇中进行研究，这些孕妇将在分娩后12个月在全国妇女联盟索尔纳妇产科诊所就诊。 我们的研究结果可能会导致怀孕饮食的修改，以降低患乳腺癌的风险。 特别是，已经处于高风险的妇女，例如，由于乳腺癌家族史，首次怀孕年龄（大于30岁）或其他生殖风险因素，可能会从怀孕饮食调整中显着受益。

Estrogen levels are elevated by 50-100 -fold during pregnancy, and inter-individual variability in pregnancy estrogen levels is 4-6 -fold. Women exhibiting highest pregnancy estrogen levels are suggested to be at a significantly increased risk to develop breast cancer, perhaps due to an estrogen-induced promotion of existing transformed cells. Diet, particularly dietary fats, may affect pregnancy estrogen levels and later breast cancer risk. In our animal study, a high fat intake significantly increased pregnancy estrogen levels and increased pregnancy-promoted mammary tumor incidence. Polymorphism in genes that metabolize estrogens and have been linked to increased breast cancer risk, may also affect pregnancy estrogen levels. Our proposed study has two general aims: (1) to study whether dietary fat intake affects pregnancy estrogen levels in women, perhaps by interacting with polymorphism in CYP17 and COMT, and (2) to study whether highest pregnancy estrogen levels might increase breast cancer risk by increasing growth factor levels. These growth factors could originate from mutated or already transformed mammary cells, which during pregnancy are stimulated by high estrogen levels. Growth factor levels will be measured in nipple aspirate fluid (NAF) that can be obtained using a breast pump from non-lactating breast. Consequently, the following hypotheses will be tested: Hypothesis-1. We hypothesize that high dietary fat intake and weight gain increase pregnancy estrogen levels. We further hypothesize that polymorphism in CYP17 or COMT influences these interactions. Hypothesis-2. We hypothesize that higher circulating estradiol levels during pregnancy are associated with increased growth factor levels in nipple aspirate fluid, including EGF, TGFalpha and IGF-1/IGF binding protein 3. These aims will be studied in 200 pregnant women attending the Maternity Clinic at Solna in NAF will be obtained 12 months after giving birth. Our results may lead to modifications of pregnancy diet to reduce the risk to develop breast cancer. In particular, women who already are at high risk, for example, due to family history of breast cancer, age at first pregnancy (greater than 30 years), or other reproductive risk factors, may significantly benefit from pregnancy dietary modifications.