Background: The NCI Patient Navigator Research Program (PNRP) is designed to assist racial/ethnic minorities, individuals with low socioeconomic status, and residents of rural areas, disproportionately affected by cancers, to obtain health care services in an affordable and timely manner. One significant challenge to fulfilling its mission is the availability of resources and services that are affordable and accessible within communities in need. Specifically, for colon cancer services, the cost and availability of screening and treatment colonoscopies represents a considerable barrier. Community partnerships and advocacy are needed to address these barriers. Objective: The aims of this study were to 1) assess the affordability of colonoscopies, 2) explore policies of charitable and discounted care, and 3) partner with community groups to identify resources and facilitate linkages and accessibility to colonoscopy screenings. Methods: An assessment of patients9 demographic information, reported symptoms, income level and insurance status was completed using data extracted from patient medical records. Additionally, reports of available services from local health systems9 providers were reviewed and summarized as a resource guide detailing guidelines and policies of local charity care. Finally, informal interviews were conducted with health institutions, navigators, and study participants to compare availability and affordability of services with patients9 preferences for services. Results: 88 colorectal cancer patients9 medical records from seven participating clinics were reviewed. The patients were predominately Hispanic, within the recommended age for colon cancer screening, uninsured, and receiving health care in medically underserved counties of central Florida. Each patient was recommended for a colonoscopy and approximately one-third received the exam via charity care. The policies and guidelines for charity care within the local healthcare systems were often not readily accessible and of those reported, many were limited in scope or non-existent. Of the systems providing colonoscopies, the cost of the exam ranged from $0 to $2200 (as a discounted rate). This study provided additional valuable information including methods of identifying community resources as well as insights into participants9 preferences for service. Conclusions: PNRP, community partnerships, and advocacy are instrumental in assisting the medically underserved in affording and utilizing healthcare services. Considerable barriers exist in accessing colorectal cancer screening and treatment services. Healthcare systems9 policies for charity care substantially facilitate the receipt of screening and treatment that prevents the unnecessary burden of cancer health disparities.
Objective: Arab Americans (ArA) are classified racially as white by many federal agencies and thus few statistics are kept on this group, but local and regional studies have shown this group is not only culturally different but may face unique health challenges. Because of racial classification as white, both numerator and denominator data are lacking. In addition, as with other minority/immigrant groups, ArA are subject to undercounting, thus rendering population estimates suspect. Therefore, little is known about cancer in this population because incidence and mortality rates cannot be calculated due to lack of numerator and denominator data. We assessed different population numbers for estimating Detroit-area ArA cancer incidence and mortality rates, while using a name list and algorithm for numerator data. Methods: Age-adjusted rates were calculated following the National Cancer Institute9s Surveillance, Epidemiology, and End Results (SEER) methodology. Numerator data (new cancers and cancer-related fatalities, 5-year average from 2000–2004) were obtained by linking the Detroit SEER database with an Arab/Chaldean surname database and algorithm previously developed and validated. For the denominator data, we used the Public-Use Microdata Sample (PUMS) from the U.S. 2000 decennial census to calculate two different population estimates. The first population estimate (ArA Pop1) used self-report of Arab or Chaldean ancestry. The second population estimate (ArA Pop2) was a combined value of Arab/Chaldean ancestry, birthplace in an Arab League country, or Arabic/Syriac language spoken at home. These responses are from the U.S. Census Bureau long form questionnaire. To assess the feasibility of calculated rates, we compared incidence and mortality rates to those published by SEER for Detroit black and white population groups. Results: Both cancer incidence and mortality rates calculated using ArA Pop2 as the denominator were comparable to published rates for Detroit black and white subpopulations. We also calculated incidence rates for the 4 most common cancers (breast, prostate, lung, colorectal), as well as overall mortality, cancer mortality and heart disease mortality. ArA Pop2 again provided comparable estimates. Confidence intervals are fairly large due to small numbers. The published rates for Detroit black and white cancers are included within the confidence intervals for ArA rates; the rates for the 3 sub-populations are similar for all sites combined and the most common cancers. Conclusions: Using a surname matching system for numerator estimates and several indicators of ArA ethnicity from a publicly available dataset to estimate the denominator provides a reasonable approximation of the cancer burden in the Detroit ArA population. This approach may work for other common chronic diseases and is useful for public health surveillance activities. It also will be helpful for health planning in geographic areas with large ArA sub-populations, such as metropolitan Detroit.
Introduction: Breast cancer is the second leading cause of cancer deaths in women. In 2008, an estimated 180,000 people will be diagnosed with breast cancer while approximately 40,000 will die from this disease. Breast cancer has been found to affect different ethnic groups disproportionately. Estrogen receptor negative (ER-) tumors are more common in AA women, when compared to Caucasian women. These aggressive tumors are more common at every age and stage of breast cancer, which causes increased mortality rate. A comprehensive approach to understand the biological factors associated with poorer outcomes among AA patients is urgently needed. We are addressing this need by investigating the role of insulin-like growth factor-II (IGF-II) in the survival disparity gap observed in AA women. ProIGF-II is a fetal growth factor regulated by estrogen to promote proliferation, prevent apoptosis and regulate energy production by signaling through the IGF-I (IGF-IR) and Insulin Receptors (IR). Methods: In our studies we used obtained four breast cancer cell lines from ATCC: AA ER−/PR− and HER2/Neu− (CRL-2335), AA ER+/PR− and Her2/Neu− (CRL-2315), Caucasian ER−/PR− and Her2/Neu+ (HS578t) and Caucasian ER+/PR+ and Her2/Neu+ (MCF-7). We evaluated the phosphorylation and subcellular localization of ER-α and ER-β, with and without proIGF-II treatment, using Real-time Polymerase Chain Reaction (RT-PCR) and western blot analysis. Results and Discussion: We have demonstrated that not only do these cell lines express ER-α and ER-β, but also the ERs become phosphorylated/activated and translocate to other cellular compartments when treated with precursor Insulin-like growth factor II (proIGF-II). Our study demonstrates that proIGF-II binding to the IGF-IR and IR can phosphorylate and activate the ER in cell membranes to stimulate a rapid non-genomic response. This activation of the estrogen receptor does not require estrogen. We report here, for the first time, that ER-α negative breast cancer cells express significant levels of ER-α and ER-β in the cytosol, membranes and mitochondria. When treated, with proIGF-II, ER-α and ER-β shifted from its predominant localization in the cytosol to the membrane/organelles and nucleus. Thus, without the requirement of estrogen binding, IGF-II can stimulate estrogen-like responses. Conclusion: We propose that proIGF-II mediates estrogen actions in these cells by phosphorylating/activating both ERs to promote estrogen independent growth and control mitochondrial and nuclear function to provide energy and cell survival proteins. Thus, IGF-II contributes to the survival disparity observed among AA breast cancer patients, because it promotes higher activation/phosphorylation of the IGF-1R and ERs. This independent activation of ERs promotes estrogen independent breast cancer cell survival and chemoresistance characteristic of triple-negative (ER−-/PR− and HER2/neu-) tumors.
To combat a significant differential in breast cancer mortality in minorities compared to whites in Washington, DC, the George Washington Cancer Institute (GWCI) instituted the DC Citywide Patient Navigation Research Program (DC-PNRP). While included among the 9 PNRP National sites funded by NCI to evaluate the effectiveness of patient navigation, the DC site is unique in its approach. Navigators from several unaffiliated clinical and community sites across DC were trained to work collaboratively to enroll patients in the research study, increase screening rates, and assure each patient receives timely, quality care. Many difficulties inherent to a complex citywide network were encountered and overcome including problems with administrative coordination, different operating procedures, and varying IRB requirements. Frequent trainings, efforts that promote increased communication between navigators, and sharing of information about community resources were implemented to enhance care coordination and to assure appropriate referral strategies such that navigators at screening sites “hand-off” patients to navigators at treatment sites. This integrative approach assures longitudinal navigation coverage for the patient from point of suspicious finding through treatment and into survivorship. It represents an innovative and creative way to address the barriers to access and underlying fragmentation of services that exist in DC for low-income uninsured or under-insured women. In developing DC-PNRP, GWCI learned that the same barriers affecting access to treatment also interfere with access to, and utilization of, screening programs, suggesting that “screening navigation” will overcome these barriers when integrated longitudinally with our outreach, education, and diagnostic services. Many reports suggest the barriers that underlie treatment disparities also contribute to survivorship disparities indicating that “survivorship navigation” integrated longitudinally with both treatment navigation and, when necessary, palliative care and end-of-life-care, may help overcome these barriers and facilitate the often stressful period of transition from active care. Hence, GWCI has developed the concept of “Longitudinal Navigation”, or navigation integrated across the full health care continuum. Our objective is to maintain the DC-PNRP framework for Network Navigation for use with other types of cancer and to expand the integrative navigation services longitudinally at both ends of the spectrum to improve health care access for all residents of the DC metro area, particularly the underserved. By increasing the effectiveness of our outreach services using navigators who will direct residents to low-cost screening facilities, those with suspicious findings will become integrated within our already established navigation network. Patients diagnosed with cancer will then be followed through the treatment process and survivorship becoming integrated within our longitudinal navigation network. Our experience with DC-PNRP has shown that navigation services positioned at various points in the healthcare system and linked to one another through systems of care coordination can reduce fragmentation, increase patient satisfaction, and improve adherence to life saving treatments.
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring subtype of lymphoma in the United States. Until 2001, chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) had been the traditional standard of care for patients with DLBCL. Beginning in 2001, published randomized , controlled clinical trials demonstrated that when rituximab (an anti-CD20 antibody immunotherapy) is added to standard CHOP chemotherapy complete response (CR) rates improved from 63% (CHOP alone) to 76% (p= 0.005), and 2-year OS improved from 57% to 70% (p = .007). However, it remains unclear how these results have influenced the use of combination chemoimmunotherapy in clinical practice. We undertook this study in order to assess differences between clinical and demographic features of patients with DLBCL who receive immunotherapy and those who do not receive immunotherapy. Methods: Data on diffuse large B cell lymphoma cases diagnosed between 2001 and 2004 were selected from the National Cancer Database, a hospital-based cancer registry jointly sponsored by the American Cancer Society and the American College of Surgeons. Patient demographics, health insurance, area-level education and income, stage of diagnosis, and facility characteristics were collected. The principle outcome of this study was receipt of immunotherapy plus chemotherapy versus chemotherapy alone. To assess other potential treatment options, two ancillary outcomes were examined 1) chemotherapy treatment versus radiation only/no treatment and 2) the receipt of some type of treatment (immunotherapy, chemo or radiation) versus no treatment. Multivariate logistic regression was performed to examine the association between race, insurance and treatment allocation, adjusting for other independent covariates. Results: The total analytic study population included 40,262 patients. Uninsured and Medicaid insured patients were less like likely to receive the recommended chemotherapy and immunotherapy (vs. chemotherapy alone) as compared to privately insured odds ratio ([OR]=0.80, 95% confidence interval [CI] 0.69–0.92;OR =0.83, 95% CI= 0.73 to 0.95, respectively). Blacks were also less likely receive recommended chemotherapy and immunotherapy (OR=0.76, 95% CI 0.69 to 0.85) compared to whites. Receiving treatment at a high volume facility was also associated with better odds of receipt of combined chemo-immunotherapy (OR 2.0, 95% CI 1.78 to 2.27). Conclusions: Our results indicate disparities exist in the receipt of recommended chemotherapy and immunotherapy for diffuse large cell lymphoma. Blacks, uninsured and Medicaid-insured patients had lower odds of receiving Rituximab with their chemotherapy.
Background: Colorectal cancer screening (CRCS) rates vary across subgroups with Hispanic Americans and uninsured populations having among the lowest levels. Recent reports also suggest that screening disparities among Hispanics persist, with a slower decline in death rates among Hispanics compared with non-Hispanic whites. Objective: To increase understanding of the barriers to CRCS in low income Hispanics, this cross-sectional study examines cultural (language and nativity), structural (financial and availability of health care), and sociodemographic factors associated with CRCS among Hispanics residing on the Texas-Mexico border. Methods: Five hundred and forty-four people meeting eligibility criteria (50 years or older, self-identified as Hispanic or Latino, and no history of cancer) were randomly recruited from colonias (unincorporated, un-zoned, semi-rural communities) in three counties along the Texas-Mexico border. Univariate and multivariate analyses using 2 tests were used to examine associations of the dependent variable, CRCS (FOBT, colonoscopy, sigmoidoscopy and barium enema), and independent variables (i.e., gender, age, birth place combined with years in the U.S., primary language spoken, household income, highest education, marital status, health insurance coverage, travel time to health care provider, and having a place for usual health care). Odds ratios and 95% confidence ratios are reported. Results: Overall, 34% of participants reported receiving any kind of CRCS. Seventy-three percent of the study participants were women and 27% were men. Mean age of participants was 63 years. Almost all (98%) were Mexican American: 77% were born in Mexico, 71% of whom have lived in the US over 20 years. Roughly 14% reported speaking English well. Only 9% were high school graduates, 72% had an annual household income of less than $10,000, and almost half had no form of health insurance coverage. The majority (73%) reported a usual place to receive health care and 89% traveled less than one hour to this provider. Factors significantly associated with any CRCS in univariate analyses included a combination variable representing nativity (birth place combined with years in the U.S.; P=0.029), health insurance (P Conclusion: Structural factors such as nativity, health insurance and having access to a usual source of health care, were significant independent risk factors for not being screened for CRC in a minority, low income Hispanic population. However, these factors were no longer significant in adjusted multivariate models. Further research is needed to understand the mediating structural and cultural barriers impacting colorectal cancer screening in this population. Findings from this research have the potential to inform policy aimed at decreasing structural barriers to improve CRCS in this population.
This paper examines cancer incidence, staging, and survivals between 1991 and 2005 by using 6 mutually exclusive race-ethnicity groups in Nebraska. The paper first assessed definition consistency, case and population changes during the study period. It is observed that Hispanic white population increased rapidly in Nebraska, and they tended to have relatively low incidence rates for most cancer sites. Some changes in incidence rates could be due to subtle differences in race-ethnicity definition used by the US Census and the NAACCR. The paper highlighted major differences in cancer burden, such as heavier and persistent burdens for prostate cancer for NH blacks, increased NH white females in lung cancer incidence, high cervical cancer incidence in Vietnamese Americans concentrated counties, and shared cancer burden Nebraska and North Plain Indians versus the general population of American Indians and Alaska Natives. It also pointed out that increased screening for several cancer sites have not translated into increased early stage diagnosis rates and five-year survival rates among the selected race-ethnicity groups. The paper also discussed difficulties of comparing results from state data and national data for detailed race-ethnicity categories. The paper evaluated the small percentage of missing race-coding (1.12%) in the cancer registry and its potential impacts on incidence rates in Nebraska, which has predominantly white population. It is suggests that the gold standard of NAACCR is not sufficient for states with 5%–8% of minority populations. It is recommended that increased effort should be made to collect race and ethnicity data cancer registry. This includes 1) cleaning and linking death certificates and other administrative data, 2) better training local tumor registrars, and 3) communicating with health professionals for better race-ethnicity probing and documentation at the frontline patient encounters. It is also suggested to use Bayesian methods for small population incidence benchmarking. The paper also made several attempts to link evidence-based cancer registry data with existing State programs that directly related to reducing cancer burden for some preliminary evaluations. Due to the fact that minority populations are concentrated in few counties in Nebraska, localized programs to reduce cancer disparity seemed more effective. It is recommended that future evidence-based program evaluations include existing population-based surveys and health care quality information, so that findings can have a direct impact on existing and future programs planning.
Purpose: To describe the incidence of prostate cancer and subsequent mortality in the predominantly African-origin population of Barbados,West Indies. This population shares a common heredity with African Americans (with lower admixture), and experiences similarly high rates of lifestylerelated noncommunicable disease. Methods: We identified all new cases of histologically confirmed prostate cancer occurring in Barbados between July 01, 2002 and December 31, 2007. We used death certification records to ascertain mortality for a 10-year period commencing January 1995. We identified prostate cancer as the underlying cause of death using nosology algorithms, and classified this cause as definite (a single listed cause, or death directly attributable to prostate cancer, including metastatic disease), or probable (multiple causes of death cited; death likely attributable to prostate cancer). Results: During the study period, 923 cases of prostate cancer were diagnosed for a rate of 158.9 (95% Confidence Interval: 148.7 – 169.6) per 100,000 standardized to the U.S. population. Comparable rates reported in the USA SEER (2000 – 2005) were 251.9 (95% CI: 249.2 – 254.6) and 158.6 (95% CI: 158.0 – 159.3) per 100,000 in African-American and White men, respectively. Age specific rates in Barbados increased from 5.3 (95% CI: 1.1 – 15.5) per 100,000 among those aged 40 to 44 to a peak at 988.7 (95% CI: 852.8 – 1140.2) per 100,000 at 70 to 74 years, declining thereafter. For the period 2002 – 2005, annual age-adjusted incidence was between 1.3 and 1.9 times higher in African American men (p Discussion: Prostate cancer incidence was lower in Barbadian than African American men, and was more comparable with rates in white American men. This may be partly due to a lower prevalence of PSA screening in Barbados with clinically more significant disease at presentation. In contrast, mortality rates in Barbadians were similar to those of African- mericans, highlighting the need for clinical and public health interventions to reduce the disproportionate disease burden.
Purpose: Colorectal cancer develops through genetic, epigenetic, and environmental events that result in uncontrolled cell proliferation. Colorectal cancer incidence and mortality is higher in African Americans (AA) than in the general population. Here, we carried out a molecular analysis of sporadic colorectal cancer tumors from AAs to investigate possible explanations for the observed disparities.Experimental Design: A total of 222 AA colorectal cancer tumors were analyzed for microsatellite instability (MSI) for protein expression of two DNA mismatch repair genes, MLH1 and MSH2, by immunohistochemistry; for the methylation silencing of MLH1, p16, APC, and APC2 promoters by methylation-specific PCR; and for point Mutations in two oncogenes, KRAS and BRAF; by sequencing.Results: In our sample, 19.8% of the AAs colorectal cancer tumors were MSI high (MSI-H) and did not associate with any of the clinicopathologic features, except tumor differentiation. Higher levels of inactive DNA mismatch repair proteins MLH1 (41%) and MSH2 (33%) were found by immunohistochemistry. Methylation-specific PCR analysis revealed a high level of methylation for MLH1 (66%), APC (53%), and APC2 (90%), but not for p16 (26%). BRAF mutations were only within the MSI-H tumors, whereas most (64%) of KRAS mutations were found within the non - MSI-H group.Conclusions: MLH1, MSH2, and BRAF alterations are significantly associated with MSI-H phenotype, unlike APC, APC2 and KRAS alterations. The prominent role of DNA mismatch repair gene suppression in MSI-H and a distinctive role of BRAF and KRAS mutations with respect to MSI status are supported by this study.
Background: Most of the estimated 12 million US cancer survivors live years after diagnosis, emphasizing the importance of health care access for survivors. Ethnic minority persons have reduced access to many health care services, but it is not known if having cancer might influence disparities. This research compares individuals with and without a history of cancer on prevalence of forgoing different types of health care services due to cost and examines whether ethnic minority survivors report poorer access to care. Method: We identified 6,602 adult cancer survivors (64.3% female; 4.8% Hispanic, 6.4% Non-Hispanic Black (NHB), 88.8% Non-Hispanic White (NHW); 57.8% more than 5 years post-diagnosis, 52.4% 65 years and older) and 104,364 individuals with no history of cancer from the United States National Health Interview Survey (NHIS)-2003–2006. The NHIS is an annual, in person, nationwide survey of approximately 30,000–40,000 households assessing many health outcomes. During the survey, individuals were asked if they did not get medical care, prescription medications, dental care, or mental health services during the past year because of concerns about cost. To account for the weighting associated with a complex sampling design, we used SUDAAN 9.0 to conduct logistic regression analyses. A significant interaction between ethnicity and cancer history would indicate that disparities among survivors differ from those in the general adult population. Results: The prevalence of forgoing care due to cost among cancer survivors was 7.8% for medical care, 9.9% for prescription medication, 11.3% for dental care, and 2.7% for mental health care. When compared with NHW survivors, Hispanic and NHB cancer survivors were more likely to forgo prescription medications (Hispanic OR = 2.14, 95% CI 1.52–3.00 & NHB OR = 1.87, 95% CI 1.38–2.54) and dental care ((Hispanic OR = 2.31, 95% CI 1.68–3.17 & NHB OR=1.57, 95% CI 1.18–2.10). Hispanic survivors were also more likely to not get medical care compared to NHW survivors (OR= 1.55, 95% CI 1.05–2.29). Disparities among cancer survivors were largely reflective of those in the general adult population. After adjusting for education, health insurance coverage, and non-cancer medical comorbidities, none of the interactions between ethnicity and cancer history were statistically significant in those persons 65 years of age and older. For those persons less than 65 years of age, there were significant interactions between Hispanic ethnicity and cancer history for forgoing dental care and prescription medications. After adjustment, Hispanic adults without a history of cancer were less likely than NHW adults to forgo medications (OR= .76, p Conclusions: More than a million cancer survivors living in the United States report that they did not get medical care that they needed because of concerns about cost. Hispanic and NHB survivors are at even greater risk of not receiving needed care. Future research needs to examine the impact of forgoing care on survivors9 long-term physical and mental well-being and survival.
Background: Colorectal cancer can be prevented via screening by the detection and removal of colorectal adenomas. Given that by the year 2030 Arizona is expected to be the tenth largest and the second fastest-growing state in the U.S., it is important to learn the extent to which this state has the colorectal screening capacity to accommodate the expected population growth. Since rural residents are less likely to receive preventive services, it is also necessary to understand capacity differences between urban and rural regions. Methods: In 2004, we surveyed 234 gastroenterologists and colorectal surgeons practicing in Arizona to assess current colonoscopy and sigmoidoscopy screening and to estimate future endoscopic capacity. In addition, we asked respondents to identify resources needed to increase capacity were identified. Differences between rural and urban regions of the state were examined. Standard descriptive statistics, including means and medians and the two-sample test of proportions were used to analyze these data. Results: The response rate was 44.9% (105/234). Responders were more likely to practice in an urban region (89.5%). Physicians reported performing 8,717 endoscopic procedures weekly (8,312 in urban and 405 in rural regions) and the vast majority were colonoscopies (91% in urban and 97% in rural regions). Urban physicians estimated being able to increase their capacity by an additional 2,968 procedures or 35.7% (95% CI 34.7–36.7) whereas rural physicians estimated an increase of 215 procedures or 53.1% (95% CI 48.1–58.0); p-value = 0.07. The most commonly cited resource needed to increase capacity in urban regions was a greater number of physicians (52.1%); whereas the top response in rural areas was appropriate compensation (54.6%). Lastly, 27.3% of rural physicians noted they did not need additional resources to increase their capacity. Conclusions: Our findings suggest that Arizona has the ability to expand the number of endoscopic procedures performed, and this potential increase in capacity was more pronounced in rural as compared to urban regions. This is an important finding given the lower screening rates reported in rural compared to urban areas in Arizona, which underscores the need to expand services to rural communities. In some cases, capacity in rural areas can be enhanced even without additional resources. Finally, findings from the present study are critical in demonstrating that accommodation of the growing population of screening-eligible residents is possible in the state of Arizona.
Human biospecimens_blood, urine, and tissue samples_are the foundation of the translational research that will transform patient care. In order for meaningful progress to occur, the biospecimens used in research must meet the highest technical and ethical standards. At present, variability pervades the collection, processing, storage, and annotation of the majority of human specimens available for research. Such heterogeneous practices lead to biospecimens of unknown molecular integrity and contribute to irreproducible research results. In today9s cancer medicine, the analysis of human biospecimens supports diagnosis, staging, and prognosis. Biospecimens will provide a critical link between molecular and clinical information for the personalized medicine of the future. Providing Guidance: The NCI Best Practices for Biospecimen Resources: Over the past several years, the National Cancer Institute (NCI) has undertaken an intensive due diligence process to understand the state of its funded biospecimen resources and the quality of biospecimens used in cancer research. In 2003, the National Biospecimen Network Blueprint was published, and an extensive examination of the NCI9s biospecimen resources was conducted the following year. During 2004–2005, the NCI established a trans-NCI Biorepository Coordinating Committee (BCC) and created the Office of Biorepositories and Biospecimen Research (OBBR) to lead and coordinate a strategic plan to confront and resolve biospecimen issues in a stepwise fashion. These efforts culminated in the development of the NCI Best Practices for Biospecimen Resources in June 2007. The NCI Best Practices identify salient guiding principles that define state-of-the-science biospecimen resource practices, promote biospecimen and data quality, and support adherence to ethical and legal requirements. The NCI Best Practices serve as an initial step towards harmonizing biospecimen resource practices and will be revised iteratively, with input from stakeholders. Education and Outreach: Refining the NCI Best Practices through Stakeholder Input: The OBBR is committed to education and outreach activities in order to ensure that the NCI Best Practices remain current and state-of-the-science. In 2007 and 2008, the OBBR launched the NCI Biospecimen Best Practices Forums to educate the cancer research community about and receive feedback on the NCI Best Practices. The Forums targeted physicians, investigators, industry representatives, hospital administrators, patient advocates, and the general public. These forums provided information about the importance of best practices in guiding biospecimen use, the operational and ethical standards in the NCI Best Practices, and resources for achieving high-quality and accessible biospecimens. In total, over 600 people attended the series of Forums. Input obtained from stakeholders during these forums will be taken into account during the development of future versions of the NCI Best Practices and new guidance documents. The NCI recognizes that some topics within the NCI Best Practices are difficult to resolve and will require extensive community input. In 2007 the OBBR held a workshop entitled “Custodianship and Ownership Issues in Biospecimen Research” to better define the parameters of custodianship that would allow biospecimen resources to operate in a culture of transparency, fairness, and accountability. The workshop convened experts from the academic community, private sector, patient advocacy groups, and government agencies to suggest recommendations about custodianship of biospecimens and associated data for NCI-supported biospecimen resources. Issues discussed at this workshop included: informed consent models, withdrawal of participation in research, custodial obligations for biospecimen resources, conflict of interest for resource staff, and intellectual property rights derived from research on biospecimens. The results of this workshop will be used to refine recommendations in the NCI Best Practices and provide further guidance to the cancer research community. The quality and availability of biospecimens impacts research efforts across the biomedical enterprise. Accordingly, the OBBR is dedicated to bringing researchers together to share knowledge and develop solutions for issues relating to biospecimen quality. Approximately 300 physicians, investigators, industry representatives and patient advocates attended the March 2008 Biospecimen Research Network Symposium, “Advancing Cancer Research through Biospecimen Quality.” The meeting featured presentations and interactive discussions from a diverse group of experts who demonstrated the critical need to address biospecimen handling variables and their impact on clinical diagnoses, drug discovery, and research and development. This symposium defined both the current scientific understanding of the biology of the biospecimen and the challenges that must be met to create evidence-based standards for human biospecimen use in translational research Developing Evidence-Based Practices: Biospecimen Research for Molecular Medicine: There is a considerable lack of scientific data assessing the effects of biospecimen handling variables on the molecular analysis of human tissues. In 2006, the OBBR received approval to establish an intramural program, the Biospecimen Research Network (BRN), to systematically address the impact of specimen handling variables on different biospecimen types and on different molecular measures. The goal of the BRN is to address these issues by sponsoring, conducting, and collaborating on studies to assess the effects of biospecimen preanalytical variables on the outcome of genomic and proteomic studies conducted for clinical diagnosis and cancer research purposes. The results of BRN research will contribute to the development of evidence-based standard operating procedures for the collection, processing, storage, and analysis of biospecimens, building on the NCI Best Practices. In June 2007, the OBBR received approval from the NCI Board of Scientific Advisors for a new extramural funding program entitled “Biospecimen Research for Molecular Medicine” (BIOREMM) to support extramural research on biospecimen science. This funding program is intended to generate the data needed to develop state-of-the-science processes that will insure the molecular integrity and clinical relevance of biospecimens used in cancer research and clinical medicine. BIOREMM will complement the existing BRN program and will consist of a range of funding mechanisms to assess the effects of variability in handling both prior to and after the biospecimen is collected. BIOREMM will also encourage researchers to find innovative solutions and approaches to issues related to quality and reproducibility. Bridging the Gap: Biospecimens and Disparity Issues: Evidence from a wide range of studies suggests that cancer patients diagnosed and treated in a setting of multi-specialty care and clinical research may live longer and have a better quality of life. The NCI Community Cancer Centers Program (NCCCP) will offer more Americans access to research-based cancer care in their home communities by affiliating with the hospitals and clinics where most cancer patients already receive care. During the three-year pilot phase, sites participating in the NCCCP will seek to bring the latest scientific advances and the highest level of innovative and integrated, multi-specialty care to a much larger population of cancer patients. The program is intended to complement other NCI initiatives in seeking to achieve four major goals: Expand clinical trials. Reduce cancer healthcare disparities. Collect, store, and share biospecimens for research. Explore the utility of a national database of electronic medical records. The availability of biospecimens representing diverse communities will help accelerate our understanding of disparities in clinical outcomes and ensure that the diagnostics and treatments developed are effective for all populations. With access to a broad cross-section of cancer patients and healthy patients participating in clinical trials, researchers will have greater opportunity to study both cancerous and normal cells provided through tissue and blood samples. The pilot will also assess how the NCI Best Practices for Biospecimen Resources can be applied nationwide to benefit the entire cancer research community. In addition to the physical quality of biospecimens, ethical, legal and social issues must also be considered. Differing social, cultural, and religious backgrounds among research participants contribute to heterogeneous views on biospecimen donation and use. Researchers and physicians must be cognizant of a donor9s cultural, religious, and racial background, while also ensuring that collected biospecimens and associated information meet the highest scientific and ethical standards. Researchers and clinicians must respect the beliefs of the communities in which they work and operate transparently in order to maintain the trust of research participants. Conclusion: Awareness of the importance of biospecimens to translational research has increased greatly and many of the collaborations necessary to advance this field have been established. Continued support and teamwork is required to fulfill the stringent requirements for high-quality and appropriately accessible biospecimens in order to advance translational research. Above all, the patient must be recognized as both an essential participant in the research process and the motivation behind advancements in cancer care.
Purpose: The aim of this study was to determine the micro-RNA (miRNA) expression profile of African American and European American prostate cancer cell lines. In addition, experimentally determine the possible functional role of those mi-RNAs determined to be significantly expressed within both groups. Experimental Design: The expression profile was investigated using novel African American and European American prostate cells with pathological stages determined to be normal, benign, metastatic, and primary tumors. The expression pattern was determine by miRNA microarray analysis and validated by Real-Time quantitative Reverse Transcription-PCR (qRT-PCR). Results: We detected 37 known miRNAs in African American androgen-dependent prostate cancer cells compared to those in European American androgen-independent prostate cancer cell lines using microarray analysis. Mir-26a was selected for validation by qRT-PCR, the results showed that African American androgen dependent cell line RC-165N/hTERT, RC-77N/hTERT and RC-77T/hTERT expressed higher levels of mir-26a compared to European American prostate cell lines. All androgen independent prostate cells DU-145, DU-145 WT, and PC-3 cells, show a substantial decrease in mir-26a compared to African American prostate cell lines. In addition, as cells lines increase in aggression in both groups, the expression of mir-26a also increased significantly, indicating that mir-26a could be a possible contributor to metastasis. Conclusion: To date, we are unaware of any studies that compare the miRNA profile in different stages of prostate cancer along with comparison within two ethnic groups, showing the importance of epigenetics in relation to such factors. Furthermore, this experiment suggests that miRNA9s could possibly contribute to the aggressiveness associated in African American patients with prostate cancer.
Background: Weight gain and obesity are associated with increased risk of postmenopausal breast cancer. Further, women who develop breast cancer and are obese have a poorer prognosis compared to women of normal weight. Regular mammography every 1–2 years has been recommended by many organizations as the gold standard for early breast cancer detection, but adherence to these recommendations may differ both by weight and race/ethnicity. In the Hawaii and Los Angeles Multiethnic Cohort (MEC) Study, only 53% of non-Hispanic White, 49% of Japanese American, 45% of Native Hawaiian, 42% of Hispanic and 44% of African American women reported having had a mammography regularly every 1–2 years over a 6-year period of follow-up. Purpose: The purpose of this study was to describe the association between body mass index (BMI) and frequency of regular mammography over an approximate 6-year period within this study after controlling for the influence of demographic and behavioral factors, and medical history. This association was examined overall and by race/ethnicity in a multiethnic cohort of women aged 45–74 years including African American, Japanese American, Hispanic, Native Hawaiian, and non-Hispanic White women. Data Analysis: The data analysis included 81,722 women from the Hawaii and Los Angeles MEC. Unconditional logistic regression was used to assess the association between BMI and regular annual or biennial (every 1–2 years) mammography overall and by race/ethnicity. Findings: The findings of the study revealed approximately 71% of MEC African American women were overweight or obese (body mass index [BMI] ≥ 25 kg/m2), followed by Native Hawaiian (65%); Hispanic (64%), non-Hispanic White (42%) and Japanese American (27%) women. Women who were overweight (OR=0.96; 95% CI 0.92–1.01) or obese (OR=0.88; 95% CI 0.84–0.93) were less likely to have regular annual mammography compared to women of normal weight. With the exception of Japanese Americans, the odds of having regular annual mammography was lower for women with BMI ≥ 25 kg/m2 compared to normal BMI for each racial/ethnic group; this association was statistically significant for non-Hispanic White, Native Hawaiian and African American women (p Conclusions: BMI is negatively associated with regular annual and biennial mammography in multiethnic women warranting the need for culturally sensitive educational strategies that promote healthy behaviors toward regular mammography and maintenance of normal BMI.
In the United States, there will be over 21,000 new cases and more than 15,000 deaths from ovarian cancer in 2008. With a 70% death rate within one year of diagnosis, ovarian cancer is righteously coined the ‘silent killer.’ Multidrug resistance (MDR) and the lack of effective alternate drug treatments pose further serious dilemmas to ovarian cancer patients. Orlistat, an anti-obesity drug, functions by inhibiting fatty acid synthase (FASN), an enzyme up-regulated in approximately 50% of cancers. Current research indicates that orlistat preferentially destroys cancer cells via an apoptotic mechanism; however, the exact pathway of orlistat-induced tumor cell death is unclear. Our objective is to elucidate the basic mechanism of orlistatinduced cell death so that an emerging class of new drugs (FASN inhibitors) can be better tailored to treat ovarian cancer patients. The ovarian cancer lines OVCAR-8 and NCI/ADR (OVCAR-8 drug-resistant) were treated with increasing concentrations of orlistat over a period of 96 hrs. We hypothesized that the MDR cells will undergo less cell death compared to the sensitive ovarian cancer cells with orlistat. Using a combination of three different cell proliferation/death assays, it was determined that MDR cells are more robust and have increased proliferative capacity compared to the OVCAR-8 cells under equivalent conditions of orlistat treatment. In contrast, additional results by immunoblotting show that orlistat can more effectively reduce FASN protein expression over time. Furthermore, orlistat can induce an endoplasmic reticulum stress-response by up-regulating GRP78/BiP. Taken together, our data demonstrates that MDR ovarian cancer cells are not as susceptible to orlistat-induced cell death despite increased FASN reduction and this suggests that alternative stress-response or survival pathways may be active.
Background and Rational: Ethnic-specific disparities in breast cancer (BC) stage of presentation and survival rates are well documented. To further investigate possible ethnic-specific genetic contributions to these disparities, we are completing gene expression profiling studies in a South Florida multiethnic cohort consisting of thirty “Triple Negative” BC patients [10 each African-American (AA), His (His) and non-Hispanic white (Cauc) women] matched for age of diagnosis and hormone receptor status, as well as in a cohort of “Triple Negative” patients from West Africa. For comparison purposes, we are conducting similar analyses in bona fide normal breast tissue surgical specimens from Cauc and AA women. The overall study aim is an increased understanding of the biological basis of ethnic-specific BC disparities, leading ultimately to individualized, ethnic-specific diagnostic and therapeutic approaches. Two immediate study goals are to demonstrate the utility of FFPE samples in obtaining consistent, reproducible data from gene expression arrays, and secondly, to identify differentially expressed genes between tumor and normal breast tissue that are common or unique among the three ethnic groups. Methods: Pathology specimens were freshly cut from FFPE blocks and marked by a pathologist as to normal vs. tumor tissue. RNA isolation, labeled cDNA preparation, and hybridization of tumor and normal cDNAs to a breast focused gene expression microarray (Breast Cancer DSA Research Tool) was performed by Almac Diagnostics. Each South Florida patient had self-matched (tumor vs. normal) tissues for gene expression studies. Results: Using 36 matched tumor and normal FFPE samples from 18 patients, approximately 17516 transcripts were detected on the Breast Cancer DSA with intensity significantly greater than background. For normal and tumor tissue samples, 9399 and 10,296 transcripts respectively, were detected in all three ethnic groups. Importantly, a subset of transcripts (hundreds to one thousand) was detected in only one or two ethnic groups. Using two-way ANOVA (disease state and ethnicity), a subset of 6479 transcripts was identified with p-value less than 0.01 in the statistical test and was selected and further used in data quality control. Data QC indicated that patient samples clustered well with respect to both ethnicity and normal versus tumor tissue. Additional analytical methods included K-means 2-Dimensional clustering and Principal Component Analysis. From these analyses, we identified ethnic-specific expression patterns in the matched normal and tumor tissue samples, which are being validated by qPCR, as well as through comparisons to data derived from the ethnically-matched normal tissues. We are refining these current studies by focusing further data analyses on lymph node negative triple negative samples, and through comparisons with similar study data from the native African samples. Summary: These analyses indicate that consistent, high quality gene expression data can be generated from FFPE samples, and that even with a small sample size, ethnic specific gene expression differences can be detected in tumor and matched normal breast tissue samples across ethnic groups. Once validated, these results have vast future implications for addressing breast cancer health disparities.
Objective: The purpose of this study was to examine levels of medical mistrust among African American, Latina and Arab American women and to assess the association between their medical mistrust and breast cancer screening behaviors. We hypothesized high levels of medical mistrust in all groups of women and a negative correlation between medical mistrust and breast cancer screening. Methods: Using community health workers from our partner health organizations a 7-item Medical Mistrust Index measured on a 4-point rating scale was administered to 341 women (116 African American, 113 Latina and 112 Arab American women). The previously validated index (reliability 0.70–0.93) was orally administered in English, Spanish or Arabic depending on the respondent9s choice. Data on breast cancer screenings and sociodemographics were also collected. We performed frequency distribution analyses to estimate the levels of medical mistrust. Bivariate associations between medical mistrust and screening behaviors were assessed using cross-tabulations and Fisher9s exact tests were employed to assess statistical significance Results: High levels of medical mistrust were found, regardless of the racial-ethnic group; more than 40% of women in any of the racial-ethnic groups agreed or strongly agreed with all the mistrust statements in the Medical Mistrust Index. For instance, 49% of the women agreed with the statement “Patients have sometimes been deceived or mislead by healthcare organizations” while 18% strongly agreed. African American women were found to have higher levels of mistrust, e.g. 39% strongly agreed with statement “Health care organizations don9t always keep your information totally private” compared to 15% for Latina and 9% for Arab American women (Chi-square = 88.960; Fisher9s exact P Conclusion: This study reveals an important association between medical mistrust and appropriately timed breast cancer screening among African American, Latina and Arab-American women. Women who had not received appropriately timed clinical breast exams were found to have higher levels of medical mistrust than those who had. Understanding medical mistrust is important for better design of tailored breast cancer screening educational programs.
Background: In 2003 the Volunteers in Medicine (VIM) clinic in downtown Jacksonville, Florida started providing free primary healthcare for low socio-economic status (income below 250% poverty level) working uninsured. VIM has now provided 18,000 patient evaluations and follows about 2,500 active patients. Volunteer physicians, ARNPs, nurses, and lay persons staff VIM to meet the needs of its patient population. VIM is funded through private and corporate donations, grants, and ongoing fundraising. Methods: VIM evaluates patients on a non-emergency appointment basis for basic care, laboratory testing, and medication dispensing. VIM partners with the community to provide free medical services: the University of North Florida (UNF) provides the ARNP Director of VIM, St. Vincent9s Health System provides free access to its extensive laboratory services and Mayo Clinic provides physician and nursing quality care as well as access to cancer clinical trials. VIM9s primary care services include mammograms, clinical breast examinations, pap smears, blood pressure testing, GI screenings, and basic laboratory testing. When results warrant further investigation, VIM refers patients to Mayo Clinic volunteer personnel for additional diagnostics and/or treatments. Results: Since 2005, 57 VIM patients were treated at Mayo Clinic: 33 patients were African American, 10 were Hispanic, 2 were of Asian descent, and 12 were Caucasian (77.2% minorities). Forty-three of the 57 (75.4%) patients were referred to Mayo Clinic because of abnormal mammogram screenings or abnormal breast examinations. Referred breast patients received chemotherapy, breast and reconstructive surgery, and radiation therapy. Overall, VIM9s referrals to Mayo Clinic generated 55 clinical trial entries in 7 separate trials. Twelve of these 57 patients were diagnosed with breast cancer and received diagnostic mammograms, ultrasounds, ultrasound-guided biopsies, stereotactic biopsies, breast MRIs, MRI-guided biopsies, and treatments as necessary at Mayo Clinic. Procedures were completed during initial visits to reduce the number of visits patients needed for diagnostic evaluations, based on feasibility. A Mayo Clinic-funded ARNP, who also volunteers at VIM, navigates the care of these patients and ensures timely patient evaluation and continuity of care at both VIM and Mayo Clinic. Conclusion: A partnership between an academic medical center and a volunteer medical clinic serving working uninsured patients can improve breast cancer disparities in a given community and increase minority representation in cancer clinical trials. Expansion and funding of similar programs will markedly ameliorate breast cancer care disparities and disparities in minority representation in cancer clinical trials.
Background: Infection with high-risk human papillomavirus (HPV) has been linked to nearly all cervical cancer. Although cervical cancer is preventable with regular screening, many women, especially in rural and low-resource areas, do not receive screening. In Cook County, which includes the city of Chicago, more than 10% of women report never having a Pap smear in their lifetime, which is notably higher than the 6.6% statewide. It is possible that the percentage of women not receiving regular pap screening is one reason why Illinois has rates of invasive cervical cancer (ICC) that are higher than the rest of the United States (9.5 vs. 8.6 persons per 100,000). In Cook County the rates are even higher 10.7/100,000 for all races and 15.8/100,000 for African Americans, with death rates following the same trend. ICC is a cancer of disparities, with a higher risk among poor, ruraldwelling, and African American, Hispanic and Native American women. For women disenfranchised from the medical community and who refuse traditional Pap smear screening, a self-administered cervico-vaginal sample (self-sampling) for HPV may aid in the identification of women at high-risk for cervical cancer. Objective: We are conducting a study of a cervico-vaginal self-sampling screening for high-risk women living in a medically underserved community of Chicago. The first step toward achieving this goal was to collect input from the African American women living in the target community. We queried women on appropriate methods for recruitment and plans for implementing this community based HPV self-sampling study. Methods: African American women who were between the ages of 30–50 years and lived in the Austin community of Chicago were recruited for two community advisory board meetings. The first group included women affiliated with the clergy and the second comprised lay community women. The advisory boards met for 2 hours, in separate closed door sessions, where they were asked to review recruitment materials, introduced to the study design and provide both oral and written comments on each. Sessions were taped as board members engaged in conversation and answered directed questions from a facilitator who works in the Austin community. Results: Advisory board members expressed several key themes. Women in the community must feel empowered by the programs slogan for it to be effective. All recruitment materials must be eye catching, women must be able to relate to its contents, and photos need to reflect images of typical community women. Recruitment should include strategies aimed at enrolling a group of women simultaneously. Community women need to feel as if this program is specifically targeting them, “that they belong”. Researchers must be accessible to the community as historical trauma impedes collaborations between the community and Universities, and should employ community members for key outreach roles. Researchers must provide a tangible service to the community and report all findings back to the community in a timely manner. Conclusions: Community advisory board members presented key concerns, and gave community perspectives that otherwise may have been overlooked in the development and implementation of this study. Advisory boards can make important contributions to research seeking to engage and enroll community members.
Introduction: Exposure to secondhand smoke (SHS) is influenced by social class and immediate personal interactions; and it occurs in various social contexts, including the living space, workplace, institutions, and other physical environments. In addition, current smokers become exposed to SHS by opting to be in areas where smoking is permitted. We examined the association between exposure to SHS and nicotine dependence. Methods: We conducted a face-to-face interview with a cross-sectional sample of 313 African-American current smokers (59% male and 41% female) age 40–86 from Baltimore City and the District of Columbia. Clinical nicotine dependence was assessed based on the Diagnostic and Statistical Manual of Mental Disorders, Text Revision (2000). Logistic regression was used to assess the association between SHS exposure setting and nicotine dependence, controlling for known confounders. Results: In a preliminary analysis, exposure to SHS at home was associated with clinical nicotine dependence (P Conclusion: These data highlight the importance of examining social contextual factors as determinants of nicotine dependence, and suggest that promotion of a smoke-free environment may reduce the prevalence of nicotine dependence among current smokers.
