Yvonne M. Coyle

The effect of environment on breast cancer risk

Environmental factors are believed to explain a large proportion of breast cancer incidence. Known risk factors for breast cancer, which are related to the reproductive life of women, and other factors, such as inheritance and socioeconomic status, explain only about half of the breast cancer cases in the US. Ionizing radiation is a well established environmental risk factor for breast cancer. Chemicals that induce mammary cancer in rodents have served as leads for studies in humans, but occupational and environmental exposure to these chemicals have for the most part lacked association with breast cancer risk. However, there is recent evidence in rats that cadmium at very low doses acts as an estrogen mimic, indicating a need to investigate the effects of metals on breast cancer risk. Studies suggest that circadian rhythm disruption is linked with breast cancer, but too few studies have been done to be conclusive. Over the years, cigarette smoking as a risk factor for breast cancer has remained controversial. However, recent research has found passive smoke exposure to be associated with increased breast cancer risk, which is hypothesized to be accounted for on the basis of an antiestrogenic effect of smoking. Solar radiation has been noted to be associated with reduced breast cancer, supporting the hypothesis that vitamin D plays a protective role in reducing this risk. Although, most of the environmental factors discussed in this review have not been convincingly found to influence breast cancer risk, research suggests that environmental exposure in combination with genetic pre-disposition, age at exposure, and hormonal milieu have a cumulative effect on breast cancer risk.

Effectiveness of a graduate medical education program for improving medical event reporting attitude and behavior

Objectives: To evaluate the effectiveness of an educational program for improving medical event reporting attitude and behavior in the ambulatory care setting among graduate medical trainees. Design: One group pre- and post-test study. Setting: The University of Texas Southwestern Medical Center at Dallas Family Medicine Residency Program. Participants: All family practice residents (n = 30). Intervention: Patient safety educational program implemented through an introductory lecture and 6 monthly conferences, June to December 2002, involving medical events that occurred in the ambulatory care setting. Outcome measures: Medical event reporting attitude and behavior at baseline and at 6 month follow up, and barriers to medical event reporting at the 6 month follow up. Results: Program attendance was significantly correlated with medical event reporting attitude and behavior change (rho = 0.525, p = 0.003). The median change in medical event reporting attitude and behavior was zero and not statistically significant (p = 0.566). Major barriers to medical event reporting were lack of time, extra paper work, and concern about career and personal reputation. Conclusions: Attending the patient safety educational program was key for promoting a positive medical event reporting attitude and behavior change among graduate trainees. Major barriers to medical event reporting were lack of time, extra paper work, and concern about career and personal reputation. Future research will need to focus on reducing these barriers and to evaluate the effectiveness of such a program over longer periods of time, since making a positive change in medical event reporting attitude and behavior must be made at the individual and organizational levels.

Role of Physical Activity in Modulating Breast Cancer Risk as Defined by APC and RASSF1A Promoter Hypermethylation in Nonmalignant Breast Tissue

Physical activity reduces breast cancer risk. Promoter hypermethylation of the tumor suppressor genes APC and RASSF1A, which is potentially reversible, is associated with breast cancer risk. We conducted a cross-sectional study in 45 women without breast cancer to determine the association of physical activity with promoter hypermethylation of APC and RASSF1A in breast tissue. We used quantitative methylation-specific PCR to test the methylation status of APC and RASSF1A, and questionnaires to assess study covariates and physical activity (measured in metabolic equivalent hours per week). In univariate analyses, the study covariate, benign breast biopsy number, was positively associated with promoter hypermethylation of APC (P = 0.01) but not RASSF1A. Mulitvariate logistic regression indicated that, although not significant, physical activities for a lifetime [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.22-1.45; P = 0.24], previous 5 years (OR, 0.62; 95% CI, 0.34-1.12; P = 0.11), and previous year (OR, 0.72; 95% CI, 0.43-1.22; P = 0.22) were inversely related to promoter hypermethylation of APC but not RASSF1A for all physical activity measures. Univariate logistic regression indicated that physical activities for a lifetime, previous 5 years, and previous year were inversely associated with benign breast biopsy number, and these results were approaching significance for lifetime physical activity (OR, 0.41; 95% CI, 0.16-1.01; P = 0.05) and significant for physical activity in the previous 5 years (OR, 0.57; 95% CI, 0.34-0.94; P = 0.03). The study provides indirect evidence supporting the hypothesis that physical activity is inversely associated with promoter hypermethylation of tumor suppressor genes, such as APC, in nonmalignant breast tissue. (Cancer Epidemiol Biomarkers Prev 2007;16(2):192–6)

Lifestyle, genes, and cancer.

It is estimated that almost 1.5 million people in the USA are diagnosed with cancer every year. However, due to the substantial effect of modifiable lifestyle factors on the most prevalent cancers, it has been estimated that 50% of cancer is preventable. Physical activity, weight loss, and a reduction in alcohol use can strongly be recommended for the reduction of breast cancer risk. Similarly, weight loss, physical activity, and cessation of tobacco use are important behavior changes to reduce colorectal cancer risk, along with the potential benefit for the reduction of red meat consumption and the increase in folic acid intake. Smoking cessation is still the most important prevention intervention for reducing lung cancer risk, but recent evidence indicates that increasing physical activity may also be an important prevention intervention for this disease. The potential benefit of lifestyle change to reduce prostate cancer risk is growing, with recent evidence indicating the importance of a diet rich in tomato-based foods and weight loss. Also, in the cancers for which there are established lifestyle risk factors, such as physical inactivity for breast cancer and obesity for colorectal cancer, there is emerging information on the role that genetics plays in interacting with these factors, as well as the interaction of combinations of lifestyle factors. Integration of genetic information into lifestyle factors can help to clarify the causal relationships between lifestyle and genetic factors and assist in better identifying cancer risk, ultimately leading to better-informed choices about effective methods to enhance health and prevent cancer.

Physical activity as a negative modulator of estrogen-induced breast cancer

Physical activity is a protective factor for breast cancer. Exposure to estrogen is an important determinant of breast cancer risk and exercise reduces estrogen levels, with the level of evidence being stronger for post-menopausal women. Possible mechanisms for estrogen induced breast cancer include increased breast epithelial cell proliferation, the metabolism of estrogen to genotoxic metabolites, such as DNA-adducts, and the silencing of tumor suppressor genes (TSGs) that have been implicated in breast carcinogenesis by inducing gene promoter hypermethylation, which is potentially reversible. Animal studies suggest that physical activity decreases breast tumor growth by promoting changes in cellular proliferation and apoptosis. Human studies provide some support for exercise producing favorable changes in estrogen metabolism that may lead to reduced breast epithelial cell proliferation. No studies have been performed to determine whether exercise decreases the accumulation of estrogen metabolite DNA-adducts in breast tissue. However, research supports the hypothesis that physical activity reduces promoter hypermethylation of TSGs implicated in breast carcinogenesis by lowering circulating estrogen levels. Thus, further research is necessary to clarify the mechanisms that relate to physical activity as a negative modulator of breast cancer risk to develop meaningful guidelines for the use of physical activity in breast cancer prevention.

An Ecological Study of the Association of Metal Air Pollutants with Lung Cancer Incidence in Texas

Background: Air pollution particulate matter and tobacco smoke, which contain metals that are human lung carcinogens, are associated with lung cancer risk. We conducted an ecological study to examine the association of metal air pollutants with lung cancer incidence in Texas. Methods: During the period 1995 to 2000, 81,132 lung cancer cases were reported in Texas. We identified eight metals that (1) are in airborne particulate matter or tobacco smoke or are human lung carcinogens and (2) had consistent Environmental Protection Agency air release reporting for multiple counties from 1988 through 2000. We examined the association of metal air releases with the average annual age-adjusted primary and non-small cell lung cancer rates in the 254 Texas counties. Results: Univariate analysis indicated the following positive associations: (1) zinc with the primary (p = 0.02) and non-small cell (p < 0.01) lung cancer rates and (2) chromium and copper with the non-small cell lung cancer rate, p = 0.01 and p = 0.01, respectively. In the multivariate analyses, risk adjusted for sex, race and ethnicity, and urbanization, zinc was positively associated with the primary (β = 0.13, p = 0.01) and non-small cell (β = 0.14, p = 0.02) lung cancer rates, and when interaction terms among the eight metals were included, zinc was significantly and positively associated with these rates. Smoking prevalence was similar for counties with and without releases for the eight metals. Conclusions: The study suggests that inhalation exposure to metals, including those that are essential human nutrients, play a role in lung carcinogenesis.

Development and initial evaluation of a culturally sensitive cholesterol-lowering diet program for Mexican and African American patients with systemic lupus erythematosus

OBJECTIVE To develop and evaluate acceptability of an intensive and ethnic-specific cholesterol-lowering diet program with a strong behavioral component in patients with systemic lupus erythematosus (SLE). METHOD A comprehensive program with a behavioral component and culturally sensitive menus was developed in an effort to alter dietary behavior in patients with SLE. Four SLE patients, 2 African American and 2 Mexican American, enrolled in this program. Data on food intake (3-day food record), acceptability of the program (subjective response), and physiologic variables were collected at baseline, 6 weeks, and 12 weeks. RESULTS The program was highly rated by all patients and found to be informative, easy to understand, ethnically sensitive, and to contain useful behavioral maintenance strategies. All 4 patients surpassed or were close to their diet goals at both 6 and 12 weeks. In this small group of patients, there was a statistically significant reduction in low-density lipoprotein cholesterol (P = 0.04) and body weight (P = 0.001), as assessed by repeated measures analysis of variance. CONCLUSION The culturally specific cholesterol-reducing diet program was highly rated and appeared to be effective in changing the diet of this small group of SLE patients, as determined by their food records and body weight. The impact of this program, including the individual components on cardiovascular disease risk factors, needs to be evaluated in a larger multiple-arm study with a lengthier intervention.

Developing Theoretical Constructs for Outcomes Research

BACKGROUND In March of 1998, The Advisory Commission on Consumer Protection and Quality in Health Industry released a report in response to the US Presidential Executive Order that recommended increasing funding for outcomes research. This report indicated that outcomes research was critical to assessing the effectiveness of treatment and the quality of care. METHODS A systematic review was conducted of the pertinent English literature that describes the development, methods, and limitations of outcomes research to identify methods for minimizing its limitations. RESULTS Current evidence indicates that approximately 80% of commonly used medical treatments have not been shown to be efficacious, primarily because the necessary randomized controlled trials have not been conducted because of methodological problems, the time required for their execution, the expense, or ethical reasons. Therefore, physicians disagree on the value of many common clinical practices, which is reflected in the large variation in medical care prescribed for different populations. Outcomes research, which is conducted under actual clinical practice conditions using effectiveness studies, offers an efficient approach for investigating the link between medical care and outcomes. However, the major limitation of past outcomes research has been its limited ability to link medical care with outcomes, because of the lack of theory development to guide the research process, inadequate data sources, or both. CONCLUSIONS The literature review suggests that the use of pertinent theoretical constructs to guide the outcomes research process will generate the results needed to assess the effectiveness of treatment and the quality of care.

Predictors of Acute Asthma Relapse: Strategies for Its Prevention

Acute asthma often requires expensive emergency department (ED) visits and hospitalizations. It is estimated that between 5% and 10% of asthmatics will have an acute exacerbation requiring a visit to the ED each year (1). Approximately one-quarter of asthmatics relapse after acute asthma care within 10 days (2–4). Previous studies indicate that recovery from acute asthma in adults occurs slowly, requiring up to 7 days in many patients (5–8). The incidence of relapse after treatment for acute asthma in children is less clear, because reported rates vary from 0% to 31% in the days to weeks after ED discharge (2,9–13). These relapses may be considered treatment failures. Hence, if patients at high risk for acute asthma relapse could be identified at the time of initial treatment for acute asthma, preventive interventions could be introduced to reduce relapse occurrence. Asthma is a chronic and common medical condition in which a patient’s environmental context must be taken into account to effectively evaluate the outcomes of care. A major focus of asthma research has been on the long-term control of asthma. However, very few studies have been performed to address the control of asthma immediately after acute asthma care. In this article we will review the previous work on predictor factors for acute asthma relapse and suggest strategies for its prevention. These factors will be reviewed according to the following categories: (1) patient sociodemographics and characteristics, (2) environment, (3) emotional and mental health status, (4) health care utilization for asthma, (5) physiological and physical health status, and (6) treatment (Table 1).

Southwestern Internal Medicine Conference: Developing Theoretical Constructs for Outcomes Research

BackgroundIn March of 1998, The Advisory Commission on Consumer Protection and Quality in Health Industry released a report in response to the US Presidential Executive Order that recommended increasing funding for outcomes research. This report indicated that outcomes research was critical to asses