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Hormonal, genetic, and environmental factors play major roles in the complex etiology of breast cancer. When treated continuously with 17[beta]-estradiol (E2), the ACI rat exhibits a genetically conferred propensity to develop mammary cancer. The susceptibility of the ACI rat to E2-induced mammary cancer appears to segregate as an incompletely dominant trait in crosses to the resistant Copenhagen (COP) strain. In both (ACI x COP)[F.sub.2] and (COP x ACI)Fe populations, we find strong evidence for a major genetic determinant of susceptibility to E2-induced mammary cancer on distal rat chromosome 5. Our data are most consistent with a model in which the ACI allele of this locus, termed Emcal (estrogen-induced mammary cancer 1), acts in an incompletely dominant manner to increase both tumor incidence and tumor multiplicity as well as to reduce tumor latency in these populations. We also find evidence suggestive of a second locus, Emca2, on chromosome 18 in the (ACI x COP)[F.sub.2] population. The ACI allele of Emca2 acts in a dominant manner to increase incidence and decrease latency. Together, Emcal and Emca2 act independently to modify susceptibility to E2-induced mammary cancer.

We examined the effect of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, á- and â-carotene (AC and BC), and á-, ä-, and ã-tocopherols (AT, DT, and GT) among 643 HIV-infected Tanzanian women. Women were randomly assigned to one of four daily oral supplements: vitamin A + BC (VA+BC); vitamins B, C, E (MV); MV + VA+BC; or placebo. Concentrations of breast milk nutrients were determined by HPLC at birth and every 3 mo thereafter. At birth, supplementation with VA+BC significantly increased the concentrations of retinol, AC, and BC by 4799, 84, and 1791 nmol/L, respectively, compared to no VA+BC (all p<0.0001). MV supplementation had no effect on AT or DT but significantly decreased GT by an average of 522 nmol/L (p=0.003). The concentrations of all nutrients decreased significantly after birth irrespective of supplementation. Retinol, AC, and BC remained significantly higher among those receiving VA+BC at 3, 6, and 12 mo compared to no VA+BC. AT was significantly higher and GT lower among women receiving MV compared to no MV at 3, 6, and 12 mo. There were no significant interactions between treatment arms. Daily supplementation with VA+BC increases retinol and carotenoid concentrations in breast milk of HIV-infected women. MV supplementation increases AT but decreases GT concentrations in breast milk. [ABSTRACT FROM AUTHOR]

Exposure to estrogens is associated with an increased risk of breast cancer. Our laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol (E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2 (estrogen-induced mammary cancer), that act independently to determine susceptibility to E2-induced mammary cancer in crosses between the susceptible ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat strain. In this study, we evaluate susceptibility to E2-induced mammary cancer in a cross between the ACI strain and the unrelated Brown Norway (BN) rat strain. Whereas nearly 100% of the ACI rats developed mammary cancer when treated continuously with E2, BN rats did not develop palpable mammary cancer during the 196-day course of E2 treatment. Susceptibility to E2-induced mammary cancer segregated as a dominant or incompletely dominant trait in a cross between BN females and ACI males. In a population of 251 female (BN x ACI)F(2) rats, we observed evidence for a total of five genetic determinants of susceptibility. Two loci, Emca4 and Emca5, were identified when mammary cancer status at sacrifice was evaluated as the phenotype, and three additional loci, Emca6, Emca7, and Emca8, were identified when mammary cancer number was evaluated as the phenotype. A total of three genetic interactions were identified. These data indicate that susceptibility to E2-induced mammary cancer in the BN x ACI cross behaves as a complex trait controlled by at least five loci and multiple gene-gene interactions.