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Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

机译:健康女性对乳腺癌的遗传易感性:乳腺癌基因突变,免疫监视和心理困扰

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The purpose of the research supported by this IDEA grant award was to test the possibility that variability in the strength of immune surveillance mechanisms against cancer (operationally defined by assessment of natural killer cell activity, or NKCA) may be a factor in determining the penetrance of mutations in breast cancer susceptibility genes. The following hypotheses were investigated: Hypothesis 1 -- Women with family histories of breast cancer are more emotionally distressed than women at normal risk, particularly after notification that they carry a mutation in a primary susceptibility gene; Hypothesis 2: Women with family histories of breast cancer will have lower levels of NK cell activity than normal risk women, which cannot be entirely attributed to the effects of higher emotional distress or the presence of a mutation in primary susceptibility genes; and Hypothesis 3: Variability in NK cell activity will contribute to variability in the penetrance of mutations in primary susceptibility genes for breast cancer. At the conclusion of the final grant year, the authors have collected psychological data on 255 women and immune data on 135 women. As their preliminary analyses have revealed, the results of the research are consistent with the hypothesis that deficits in immune surveillance (e.g., as a result of stress) moderate the effects of mutations in primary susceptibility genes. The study could have important implications for the eradication of breast cancer. These results raise the possibility that appropriate interventions to reduce stress and increase the activity of immune surveillance mechanisms in women carrying mutations in primary susceptibility genes might delay the onset or prevent the development of breast cancer.

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