The Role of Glucocorticoid Receptor in the Racial/Ethnic Disparity of Aggressive Breast Cancer

Breast cancer is the most common malignancy and the second leading cause of cancer-related death in women worldwide. There is a well-documented variation in breast cancer incidence and mortality across nations and among racial/ethnic groups within these nations. In the United States, the incidence of breast cancer is lower among African American and Hispanic women when compared with white women, yet, as a group African American and Hispanic women have a more aggressive disease at diagnosis and worse survival outcomes. The reasons for racial disparity in breast cancer mortality are largely unknown but likely multifactorial involving environmental and biological factors. A number of epidemiological studies have shown that the cellular alterations resulting from chronic psychosocial stress may increase breast cancer development and progression. One of the primary mediators of stress is glucocorticoid. Glucocorticoid is a steroid hormone with a physiological and pathological role in the body; it acts via its cytoplasmic receptor, the glucocorticoid receptor (GCR). Upon binding to glucocorticoid, GCR is activated and released from a chaperone complex. Activated GCR travels to the nucleus to regulate a myriad of physiological processes such as mammary development and differentiation, inflammation, apoptosis as well as glucose and fatty acid metabolism-processes which have been associated with breast cancer development and progression. The main hypothesis is that alterations in the level or localization of GCR might interfere with the glucocorticoid response, resulting in aberrant downstream cellular responses such as decreased apoptosis and chronic inflammation that might contribute to aggressive breast cancer. And if these characteristics vary by race/ethnicity then this may play a role in the pathogenesis of the racial/ethnic disparity of breast cancer. The overarching theme of this research is to understand the role of GCR in breast cancer and its potential involvement in racial/ethnic disparities. To answer our research question, we used data from the Breast Cancer Care in Chicago (BCCC), a large, multiethnic population of incident breast cancer cases between the ages of 30 and 79 with stored biological samples and linked clinical, genetic ancestry and sociodemographic data

Summary of the meta-analyses for the association of zinc and prostate cancer.

<p>Summary of the meta-analyses for the association of zinc and prostate cancer.</p

Flow diagram of systematic literature search on zinc and the risk of prostate cancer.

<p>Flow diagram of systematic literature search on zinc and the risk of prostate cancer.</p

Forest plot of included studies for the highest versus lowest meta-analysis, stratified by zinc intake (dietary, supplement, and total) or zinc status (serum, nail, and hair).

<p>Forest plot of included studies for the highest versus lowest meta-analysis, stratified by zinc intake (dietary, supplement, and total) or zinc status (serum, nail, and hair).</p

Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis

<div><p>Zinc is an essential dietary element that has been implicated in the pathogenesis of prostate cancer, a cancer that disproportionately affects men of African descent. Studies assessing the association of zinc intake and prostate cancer have yielded inconsistent results. Furthermore, very little is known about the relationship between zinc intake and prostate cancer among African Americans. We examined the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study of African Americans. We then compared our results with previous studies by performing a meta-analysis to summarize the evidence regarding the association between zinc and prostate cancer. Newly diagnosed African American men with histologically confirmed prostate cancer (n = 127) and controls (n = 81) were recruited from an urban academic urology clinic in Washington, DC. Controls had higher zinc intake, with a mean of 14 mg/day versus 11 mg/day for cases. We observed a non-significant, non-linear increase in prostate cancer when comparing tertiles of zinc intake (OR _{<6.5 vs 6.5–12.5mg/day} 1.8, 95% CI: 0.6,5.6; OR _{<6.5 vs >12.5mg/day} 1.3, 95% CI: 0.2,6.5). The pooled estimate from 17 studies (including 3 cohorts, 2 nested case-control, 11 case-control studies, and 1 randomized clinical trial, with a total of 111,199 participants and 11,689 cases of prostate cancer) was 1.07_{hi vs lo} 95% CI: 0.98–1.16. Using a dose-response meta-analysis, we observed a non-linear trend in the relationship between zinc intake and prostate cancer (p for nonlinearity = 0.0022). This is the first study to examine the relationship between zinc intake in black men and risk of prostate cancer and systematically evaluate available epidemiologic evidence about the magnitude of the relationship between zinc intake and prostate cancer. Despite of the lower intake of zinc by prostate cancer patients, our meta-analysis indicated that there is no evidence for an association between zinc intake and prostate cancer.</p></div

Dose-response relations between zinc intake and RR of prostate cancer (P for nonlinearity = 0.0022).

<p>The fitted nonlinear trend is represented by the solid line with the 95% confidence intervals line in long dashes. Lines with short dashes represent the linear trend.</p

Demographic and health-related characteristics of the Washington D.C. prostate cancer study by outcome.

<p>Demographic and health-related characteristics of the Washington D.C. prostate cancer study by outcome.</p

Characteristics of papers included in the meta-analysis.

<p>Characteristics of papers included in the meta-analysis.</p

Sensitivity analysis investigating the influence of each individual study on the overall meta-analysis of zinc and risk of prostate cancer.

<p>The meta-analysis of all studies except the “omitted” study named on the left margin is presented as a horizontal confidence interval. The full, “combined” results are shown as the solid vertical lines.</p

Funnel plot of studies examining the association between zinc and prostate cancer incidence as a test for publication bias.

<p>Funnel plot of studies examining the association between zinc and prostate cancer incidence as a test for publication bias.</p