Pregnancy Estrogens, Diet, and Breast Cancer Risk

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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.