Pregnancy estrogens, diet, and markers of possible breast cancer risk

A woman's breast exhibits varying sensitivity to estrogens and possible other hormones and growth factors during her life-time. For example, an exposure to elevated estrogen levels during fetal life may imprint the breast to become more susceptible to malignant transformation.

Project description

Exposure during childhood and adolescence might induce early differentiation of the breast, and reduce susceptibility to breast cancer. This is evident through findings that pregnancy, which is characterized by both high estrogen levels and marked differentiation of the breast, occurring prior to age 18, is associated with lower life-time breast cancer risk. However, first pregnancy that occurs after age 30 is associated with a life-time increase in breast cancer. Further, pregnancy induces a short-term increase in risk, lasting approximately 5 years after pregnancy, in women who are 25 or older at first pregnancy. There is evidence to suggest that higher pregnancy estrogenicity is associated with increased breast cancer risk. Thus, women who took diethylstilbestrol or suffered from severe nausea, exhibit increased breast cancer risk. Women with low pregnancy estrogens who suffered from hypertension/pre-eclampsia, exhibit reduced breast cancer risk. Estrogen levels are approximately 50-100 times higher in pregnant than in non-pregnant women, but the levels also exhibit a marked inter-individual variability (4-6 fold) during pregnancy.

It is critical to identify factors that contribute to the normal inter-individual variability in pregnancy estrogen levels. Diet, particularly dietary fats, may affect pregnancy estrogen levels. Data obtained in women indicate that obesity is associated with high circulating estrogen levels, while low fat intake reduces circulating estrogens.

Project status: Completed
Main financing: NIH, Cancerfonden

Project leader

Partners

  • Leena Hilakivi-Clarke (Georgetown University, Washington DC, USA), co-PI, responsible for all laboratory assays
  • Marie Löf, Karolinska Institutet, associate professor, nutritionist

Research group

Marie Löf, Associate professor

Sven Sandin, Statistician

Pouran Almstedt, Database manager

Publications

Trimester-specific reference intervals for thyroxine and triiodothyronine in pregnancy in iodine-sufficient women using isotope dilution tandem mass spectrometry and immunoassays.
Soldin OP, Hilakivi-Clarke L, Weiderpass E, Soldin SJ
Clin. Chim. Acta 2004 Nov;349(1-2):181-9

Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry.
Soldin OP, Guo T, Weiderpass E, Tractenberg RE, Hilakivi-Clarke L, Soldin SJ
Fertil. Steril. 2005 Sep;84(3):701-10

Effects of pre-pregnancy physical activity and maternal BMI on gestational weight gain and birth weight.
Löf M, Hilakivi-Clarke L, Sandin S, Weiderpass E
Acta Obstet Gynecol Scand 2008 ;87(5):524-30

Dietary fat intake and gestational weight gain in relation to estradiol and progesterone plasma levels during pregnancy: a longitudinal study in Swedish women.
Lof M, Hilakivi-Clarke L, Sandin S S, de Assis S, Yu W, Weiderpass E
BMC Womens Health 2009 Apr;9():10

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