Lifetime changes in body mass index and risk of breast cancer in minority women

Introduction: Obesity is an epidemic in the United States, especially among Hispanics and African-Americans. Studies of obesity and breast cancer risk and subtype have been conducted primarily in non-Hispanic whites. Obesity is inversely associated with premenopausal breast cancer, but both obesity and weight gain increase the risk of postmenopausal disease. Obesity has been associated with breast cancer subtype in many studies. Methods: To assess the association between changes in body mass index (BMI) over the lifetime, weight gain, and breast cancer in Mexican-American women, we conducted a case-control study using 149 cases and 330 age-matched controls. In a second study, we identified 212 African-American and 167 Mexican-American women with breast cancer in the ongoing ELLA Bi-National Breast Cancer Study, abstracted medical charts to classify tumors as ER+/PR+, HER2+, or ER-/PR-/HER2-, and assessed the association between lifetime changes in body mass index, weight gain, and breast cancer subtype. In both studies, growth mixture modeling was use to identify trajectories of change in BMI over the lifetime, and these trajectories were used as exposures in a logistic regression model to calculate odds ratios (OR). Results: There was no association between trajectories of change in BMI and breast cancer risk in Mexican-American women. In addition, BMI at ages 15 and 30 and at diagnosis was not associated with breast cancer. However, adult weight gain was inversely associated with breast cancer risk (per 5kg, OR=0.92, 95% CI: 0.85-0.99). The case-only analysis found no association between obesity at ages 15 and 30 and at diagnosis and breast cancer subtype. Further, there was no association between adult weight gain (defined as weight change from age 15 to time of diagnosis) and breast cancer subtype. Conclusions: Obesity was not associated with breast cancer risk in Mexican-American women, while adult weight gain reduced the risk independently of menopausal status. These results are contradictory of those in non-Hispanic white women and suggest that the etiology of breast cancer may differ by race/ethnicity. Further, obesity was not associated with breast cancer subtype in African-American and Mexican-American women, contrary to results in non-Hispanic white women. ^

Cardiovascular disease risk factors in Hispanic children identified through a diabetic proband

Prevalence and mortality rates for non-insulin dependent (Type II) diabetes mellitus are two to five times greater in the Mexican-American population than in the general U.S. population. Diabetes has been associated with risk factors which increases the likelihood of developing atherosclerosis. Relatives of noninsulin dependent diabetic probands are at increased risk of developing diabetes; and offspring of diabetic parents are at greater risk. Elevation in risk factor levels clearly began to develop prior to adulthood. Therefore an excess of these risk factors are expected among offspring and relatives of diabetics.^ The purposes of this study were to describe levels of risk factors within a group of Mexican American children who were identified through a diabetic proband, and to determine if there was a relationship between risk factor levels and heritability. Data from three hundred and seventy-six children and adolescents between the ages of 7 and 13 years, inclusively, were analyzed. These children were identified through a diabetic proband who participated in the Diabetes Alert Study. This study group was compared to a representative sample of Mexican American children, who participated in the Hispanic Health and Nutrition Examination Survey.^ For females, there were statistically significant associations between upper body fat distribution and increased systolic and diastolic blood pressure after adjusting for age and measures of fatness. Body mass index was positively related to and explained a significant portion of the variability in systolic blood pressure, total cholesterol, and HDL-cholesterol, for males only. No relationship was found between degree of relationship to the diabetic proband and risk factor levels. The most likely explanations for this were insufficient sample size to detect differences, and/or incomplete ascertainment of pedigree information.^ Although there was evidence that these Mexican American children are fatter and have more central fat distribution than non-Hispanic children, there is no evidence of increased risk for diabetes and/or cardiovascular disease at these ages. ^

Bayesian and survival model for tumor relapse status and disease-specific survival, with applications to breast cancer

Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. Studies on ipsilateral breast tumor relapse (IBTR) status and disease-specific survival will help guide clinic treatment and predict patient prognosis.^ After breast conservation therapy, patients with breast cancer may experience breast tumor relapse. This relapse is classified into two distinct types: true local recurrence (TR) and new ipsilateral primary tumor (NP). However, the methods used to classify the relapse types are imperfect and are prone to misclassification. In addition, some observed survival data (e.g., time to relapse and time from relapse to death)are strongly correlated with relapse types. The first part of this dissertation presents a Bayesian approach to (1) modeling the potentially misclassified relapse status and the correlated survival information, (2) estimating the sensitivity and specificity of the diagnostic methods, and (3) quantify the covariate effects on event probabilities. A shared frailty was used to account for the within-subject correlation between survival times. The inference was conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in softwareWinBUGS. Simulation was used to validate the Bayesian method and assess its frequentist properties. The new model has two important innovations: (1) it utilizes the additional survival times correlated with the relapse status to improve the parameter estimation, and (2) it provides tools to address the correlation between the two diagnostic methods conditional to the true relapse types.^ Prediction of patients at highest risk for IBTR after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The goals of the second part of this dissertation were to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center, to determine the risk of IBTR in patients with DCIS treated with local excision, and to determine whether there is a subset of patients at low risk of IBTR. Patients who had undergone local excision from 1990 through 2007 at MD Anderson Cancer Center with a final diagnosis of DCIS (n=794) were included in this part. Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients with complete data. Nomogram for prediction of 5- and 10-year IBTR probabilities were found to demonstrate imperfect calibration and discrimination, with an area under the receiver operating characteristic curve of .63 and a concordance index of .63. In conclusion, predictive models for IBTR in DCIS patients treated with local excision are imperfect. Our current ability to accurately predict recurrence based on clinical parameters is limited.^ The American Joint Committee on Cancer (AJCC) staging of breast cancer is widely used to determine prognosis, yet survival within each AJCC stage shows wide variation and remains unpredictable. For the third part of this dissertation, biologic markers were hypothesized to be responsible for some of this variation, and the addition of biologic markers to current AJCC staging were examined for possibly provide improved prognostication. The initial cohort included patients treated with surgery as first intervention at MDACC from 1997 to 2006. Cox proportional hazards models were used to create prognostic scoring systems. AJCC pathologic staging parameters and biologic tumor markers were investigated to devise the scoring systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort to validate the scoring systems. Binary indicators for pathologic stage (PS), estrogen receptor status (E), and tumor grade (G) were summed to create PS+EG scoring systems devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups than the current AJCC staging system. The ability of the PS+EG score to stratify outcomes was confirmed in both internal and external validation cohorts. The current study proposes and validates a new staging system by incorporating tumor grade and ER status into current AJCC staging. We recommend that biologic markers be incorporating into revised versions of the AJCC staging system for patients receiving surgery as the first intervention.^ Chapter 1 focuses on developing a Bayesian method to solve misclassified relapse status and application to breast cancer data. Chapter 2 focuses on evaluation of a breast cancer nomogram for predicting risk of IBTR in patients with DCIS after local excision gives the statement of the problem in the clinical research. Chapter 3 focuses on validation of a novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention. ^

The relationship of obesity and cardiovascular disease

Aim. To review published literature on the relationship of obesity and cardiovascular disease.^ Methods. To look at all the studies published on the topic from 2005.^ Results. In the studies done prior to 2011, body mass index and in particular waist to hip ratio (51.57) was found to be associated with coronary heart disease. But, this relationship was challenged by the latest Lancet 2011meta-analysis 1 which concluded that singly or in combination, body-mass index, waist circumference, and waist-to-hip ratio did not importantly improve prediction of first-onset cardiovascular disease when additional information exists on blood pressure, history of diabetes, and cholesterol measures were available. Furthermore, they also found long-term reproducibility of BMI to be superior to that of waist-to-hip ratio (or waist circumference). Interestingly, body mass index in later childhood and early adult life showed positive association with coronary heart disease later in life 2. In US female health professionals 3 increasing body mass index was found to be associated with increased coronary heart disease risk. Overall 4, physical activity was found to be independently associated with fewer risk factors, less coronary artery disease, and fewer adverse events in women. Finally, obesity was found to be associated with increased overall cardiovascular mortality and coronary heart disease mortality 5.^ Conclusions. There is insufficient data to draw guidelines regarding parameters of obesity affecting cardiovascular disease. But there is data to support that lower body mass index would lead to decreased cardiovascular disease mortality. And physical activity has a direct association with less coronary artery disease in women.^

Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred

Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mnl1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease.

Lipotoxic heart disease in obese rats: Implications for human obesity

To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.

Health-related quality of life and determinant factors in celiac disease. A population-based analysis of adult patients in Spain

Background: Celiac disease (CD) has a negative impact on the health-related quality of life (HRQL) of affected patients. Although HRQL and its determinants have been examined in Spanish CD patients specifically recruited in hospital settings, these aspects of CD have not been assessed among the general Spanish population. Methods: An observational, transversal study of a non-randomized, representative sample of adult celiac patients throughout all of Spain's Autonomous Regions. Subjects were recruited through celiac patient associations. A Spanish version of the self-administered Celiac Disease-Quality of Life (CD-QOL) questionnaire was used. Determinant factors of HRQL were assessed with the aid of multivariate analysis to control for confounding factors. Results: We analyzed the responses provided by 1,230 patients, 1,092 (89.2%) of whom were women. The overall mean value for the CD-QOL index was 56.3 ± 18.27 points. The dimension that obtained the most points was dysphoria, with 81.3 ± 19.56 points, followed by limitations with 52.3 ± 23.43 points; health problems, with 51.6 ± 26.08 points, and inadequate treatment, with 36.1 ± 21.18 points. Patient age and sex, along with time to diagnosis, and length of time on a gluten-free diet were all independent determinant factors of certain dimensions of HRQL: women aged 31 to 40 expressed poorer HRQL while time to diagnosis and length of time on a gluten-free diet were determinant factors for better HRQL scores. Conclusions: The HRQL of adult Spanish celiac subjects is moderate, improving with the length of time patients remain on a gluten-free diet.

The conception of disease : its history, its versions, and its nature /

Includes index.

Men and heart disease : an atlas of racial and ethnic disparities in mortality /

Includes bibliographical references and index.

Standard hand-book of household economy for the people : comprising plain directions for the management of a family, servants, lying-in room, nursery, sick-room, flower-garden, and household pets, and also, for the preparation and administration of remedies for disease /

Includes index.

Ralston gardens of life : a study of health and the best way of living, including the natural cure of disease and the perfecting of the faculties : also private walks and talks with the author and a complete presentation of diets in health and disease and foods of the Ralstonites /

Includes index.

National death index user's manual.

Shipping list no.: 98-0050-P.

Armillaria root disease /

Includes index.

House-flies and how they spread disease /

Includes bibliographical references and index.

Contagious bovine pleuropneumonia and Mycoplasma mycoides var. mycoides, 1852-1968 : a bibliography and index ; appendix 1969-April 1970 /

Kept up to date by supplements.