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    Article: How will GINA influence participation in pharmacogenomics research and clinical testing?
    L G Dressler, S F Terry
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    ABSTRACT: After a 13-year battle in Congress--longer than it took to map the human genome--the Genetic Information Nondiscrimination Act (GINA) was passed into law on 21 May 2008. Before its passing, Francis Collins, then director of the National Human Genome Research Institute, testified before the 110th Congress that the success of personalized medicine hinged on the passing of the legislation. How will GINA, which takes effect in 2009, influence participation in pharmacogenomic research and clinical testing?
    Clinical Pharmacology &#38 Therapeutics 11/2009; 86(5):472-5. · 6.04 Impact Factor
  • Article: Reproductive factors in relation to breast cancer characterized by p53 protein expression (United States).
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    ABSTRACT: To evaluate the potential etiologic heterogeneity of breast cancer by examining whether associations with reproductive and other personal characteristics differed by p53 protein expression status. Data from the Carolina Breast Cancer Study, a population-based, case-control study of 861 cases and 790 controls, were utilized. Immunohistochemical staining for the p53 protein was performed on 638 archived tumor specimens; 46% of cases were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for p53+ and p53- breast cancer relative to controls for reproductive and other personal characteristics. Analyses were performed separately for younger (< or = 45 years) and older (>45 years) women. Risk factor profiles largely overlapped for p53+ and p53- breast cancer, with the exception of oral contraceptive (OC) use among younger women and a family history of breast cancer. Prolonged OC use was more strongly associated with p53+ breast cancer [OR 3.1 (95% CI: 1.2-8.1) than p53- breast cancer (OR 1.3 (95% CI: 0.6-3.2)] among younger women only. A first-degree family history of breast cancer was associated with p53+ breast cancer among younger women [OR 1.5 (95% CI: 1.0-2.2)] and older women [OR 1.4 (95% CI: 0.9-2.3)], but not p53- breast cancer in either age-group. These results provide little evidence of breast cancer heterogeneity as classified by p53 expression status. However, although not statistically significant, OC use among younger women and family history of breast cancer may operate through a pathway involving p53 alterations to increase risk of breast cancer.
    Cancer Causes and Control 09/2003; 14(7):609-18. · 2.88 Impact Factor
  • Article: Reproductive factors in relation to breast cancer characterized by p53 protein expression (United States)
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    ABSTRACT: Objective: To evaluate the potential etiologic heterogeneity of breast cancer by examining whether associations with reproductive and other personal characteristics differed by p53 protein expression status. Methods: Data from the Carolina Breast Cancer Study, a population-based, case–control study of 861 cases and 790 controls, were utilized. Immunohistochemical staining for the p53 protein was performed on 638 archived tumor specimens; 46% of cases were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for p53+ and p53– breast cancer relative to controls for reproductive and other personal characteristics. Analyses were performed separately for younger (45 years) and older (>45 years) women. Results: Risk factor profiles largely overlapped for p53+ and p53– breast cancer, with the exception of oral contraceptive (OC) use among younger women and a family history of breast cancer. Prolonged OC use was more strongly associated with p53+ breast cancer [OR 3.1 (95% CI: 1.2–8.1) than p53– breast cancer (OR 1.3 (95% CI: 0.6–3.2)] among younger women only. A first-degree family history of breast cancer was associated with p53+ breast cancer among younger women [OR 1.5 (95% CI: 1.0–2.2)] and older women [OR 1.4 (95% CI: 0.9–2.3)], but not p53– breast cancer in either age-group. Conclusions: These results provide little evidence of breast cancer heterogeneity as classified by p53 expression status. However, although not statistically significant, OC use among younger women and family history of breast cancer may operate through a pathway involving p53 alterations to increase risk of breast cancer.
    Cancer Causes and Control 01/2003; 14(7):609-618. · 2.88 Impact Factor
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    Article: Environmental factors in relation to breast cancer characterized by p53 protein expression.
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    ABSTRACT: Findings from studies of cigarette smoking and low-dose ionizing radiation exposure and breast cancer are unclear. Laboratory studies indicate that both exposures can cause DNA damage, potentially increasing cancer risk if such mutations occur in growth control genes, such as p53. We examined the potential etiologic heterogeneity of breast cancer by evaluating whether associations between cigarette smoking and low-dose ionizing radiation and breast cancer differed by p53 protein expression status. Data were obtained from the Carolina Breast Cancer Study, a population-based, case-control study conducted among African-American and white women ages 20-74 years. Questionnaire data were available from 861 women with incident, primary invasive breast cancer and 790 community-based controls. p53 immunostaining was performed on tissue from 683 women with breast cancer; 46% were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (ORs) for p53+ and p53- breast cancer, as compared with controls, in relation to smoking and low-dose ionizing radiation exposure. Smoking was not differentially associated with p53+ or p53- breast cancer, even when duration, dose, and passive smoking status were considered. Exposure to individual sources of radiation did not differ for p53+ and p53- breast cancers. However, ORs for combined exposure to chest X-rays and occupational radiation were higher for p53+ [OR, 2.2; 95% confidence interval (CI), 1.0-5.3] than p53- breast cancer (OR, 1.2; 95% CI, 0.5-3.4). Combined exposure to radiation from other medical sources as well as occupational exposure was also higher for p53+ (OR, 3.7; 95% CI, 0.8-16.8) than for p53- breast cancer (OR, 1.7; 95% CI, 0.3-10.5). Although preliminary, our results suggest that exposure to multiple sources of low-dose ionizing radiation may contribute to the development of p53+ breast cancer.
    Cancer Epidemiology Biomarkers &amp Prevention 10/2002; 11(9):829-35. · 4.12 Impact Factor
  • Article: Handling, storage, and preparation of human tissues.
    L G Dressler, D Visscher
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    ABSTRACT: Human tissue for flow cytometry must be prepared as an adequate single-cell suspension. The appropriate methods for tissue collection, transport, storage, and dissociation depend on the cell parameters being measured and the localization of the markers. This unit includes a general method for collecting and transporting human tissue and preparing a tissue imprint. Protocols are supplied for tissue disaggregation by either mechanical or enzymatic means and for preparation of single-cell suspensions of whole cells from fine-needle aspirates, pleural effusions, abdominal fluids, or other body fluids. Other protocols detail preparation of intact nuclei from fresh, frozen, or paraffin-embedded tissue. Support protocols cover fixation, cryospin preparation, cryopreservation, and removal of debris.
    Current protocols in cytometry / editorial board, J. Paul Robinson, managing editor ... [et al.] 06/2001; Chapter 5:Unit 5.2.

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