bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B116: Comparison of African American (AA) and Caucasian patients with respect to radiotherapy (RT) delivery in National Surgical Adjuvant Breast & Bowel Project (NSABP) breast cancer treatment trials
Authors: Thomas Charles R. , Glover Khaleelah Z. , Wilson John W. , Feingold Eleanor , Constantino John P.
Published: December 2010

Purpose/Objective(s): Outcomes in racial disparities among cancer patients (pts) is established. The specific aim of this study was to determine if RT delivery differed by race as measured by total dose, duration of RT, and dose-intensity (DI), in a major cooperative group dataset.

Methods and Materials: 9,646 Caucasian (C) pts & 1,040 African-American (AA) pts were enrolled in NSABP breast cancer protocols: B15, B16, B18, B22, B23, B25, & B28. Adjuvant AC was given in all protocols. Within the total cohort, 3,504 C pts & 377 AA pts received RT. Statistical methodology: Logistic regression was used as the method of analysis. The dependent, or outcome, variables were binary (Y/N): total dose at least 5,000 Gy, RT duration < 35 days, & DI at least 142.86 (= 50 Gy/35 days). The primary predictor variable was race (AA vs C). Potential confounder variables considered were race, age, no. of positive nodes (0,1-3,4-9,10+), completion of 4 cycles of AC (Y/N), pathologic tumor size, & protocol. Association between race & outcome was initially assessed without adjustment. Next, logistic regression models were constructed in a forward stepwise fashion, considering the above potential confounder variables in turn, using α = 0.05 for entry & removal. For all 3 outcomes, the only potential confounder variable that reached significance in the stepwise analysis was protocol. Finally, race & race-by-protocol interaction were added to the models & assessed for statistical significance.

Results: Most pts completed the recommended dose [n=331 AA (87.7%); 3,182 C (90.8%)] within the recommended number of days (< 35) per protocol [327 AA (86.7%), 3,096 C (88.3%)] & received the appropriate Dl [296 AA (78.5%), 2,860 C (81.6%)]. Race was not a significant univariate predictor for total dose (p=0.06, 0R=0.73; 95% Cl=0.52−1.01) & did not reach significance after adjustment for protocol (p=0.07, 0R=0.73, Cl=0.52−1.02). Race was not a predictor for completion of RT within 35 days (p=0.35, 0R=0.86, Cl=0.63 −1.18) & remained non-significant after adjustment for protocol (p=0.51, 0R=0.90, Cl=0.66–1.23). As a univariate predictor of RT Dl, race was not significant (p=0.16, 0R=0.83, Cl=0.64–1.08). After adjustment for protocol, race remained non-significant (p=0.25, 0R=0.86, Cl=0.66–1.12). The interaction between race & protocol was non-significant for all outcomes.

Conclusions: Randomized trials guide evidence-based approaches for breast cancer treatment. This study did not find evidence of racial disparity in the delivery of RT in NSABP breast cancer trials examined.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B116.
Abstract B17: Providing access and reducing barriers to mammography use in an underserved area
Authors: Drake Bettina F. , Tannan Shivon , Anwuri Victoria , Colditz Graham
Published: December 2010

Purpose: A federally-qualified health care center (FQHC) and a university in St. Louis, MO have partnered to increase access and reduce barriers to mammography in an underserved area. The purpose of this study is 1. to assess the barriers to mammography use in this underserved population; 2. the proportion of women in this population who are uninsured and do not quality for governmental assistance; 3. the previous lack of compliance to mammography among the women currently being navigated.

Background: Even though black women have higher rates of utilizing mammography services than that of white women in Missouri, black women's mortality rate is much higher in comparison to other groups and it is steadily increasing. This data reflects the importance of continuing to encourage routine mammography use among minority and underserved women in accordance with screening recommendations. The female patient population of the target clinic is 87.0% black and has a disproportionate number of women who were due or overdue for a mammogram (87.7%).

Methods: The FQHC, Betty Jean Kerr People's Health Centers, has instituted a mammography screening program in one of its clinics that previously did not provide mammography services. The university, through the Program for the Elimination of Cancer Disparities, provides training in patient navigation as well as financial assistance for uninsured participants who do not qualify for governmental co-payment assistance. The patient navigator assists women, age 40 and over in determining their eligibility for financial assistance, scheduling appointments, as well as any follow-up services. If the participant is uninsured and does not qualify for co-payment assistance, a study voucher is provided. All navigated women are surveyed on barriers to mammography use as well as the date of their last mammogram. Results: To date, 309 women have been navigated through the clinic. 65% report cost as a barrier. 72% of the navigated women are uninsured. Among those uninsured, 13% also do not qualify for state co-pay assistance. Of the women currently navigated, 60% were non-compliant for a mammogram, having a mammogram over 1 year previously. Among these women, 53%, 21%, and 25% of women were non-compliant for 1, 2 and 3 or more years respectively.

Conclusions: There is a need for increased access to mammography in underserved areas. Even when access is achieved, financial barriers remain. FQHCs can subsidize these services, however even co-payments can be financial barriers for some uninsured women and there is a proportion of uninsured women who do not qualify for governmental assistance for co-payment.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B17.
Abstract B2: Educational intervention to reduce breast cancer disparities: The Dallas Cancer Disparities Community Research Coalition
Authors: Cardarelli Kathryn M. , Haley Sheila , Linnear Kim , Jackson Rachael , Martin Marcus , Lopez Roy , Senteio Charles , Weaver Preston , Hill Anna , Banda Jesse , Epperson-Brown Marva , Morrison Janet , Parrish Deborah , Newton Johnrice , Royster Marcene , Lafayette Camille , Harris Phyllis , Vishwanatha Jamboor K. , Johnson Eric S.
Published: December 2010

Purpose: South Dallas experiences significant disparities in breast cancer mortality, with a high proportion of stage III and IV diagnoses. In an effort to address these rates, the Dallas Cancer Disparities Community Research Coalition created an educational intervention in 2009 to promote breast health and early detection efforts. The goals of the intervention were to increase: (1) knowledge regarding the chief contributing factors for breast cancer and steps to reduce breast cancer risk; (2) awareness of the importance of screening for early detection; and (3) the proportion of women who have engaged in appropriate breast cancer screening practices. The innovation of the project lies in the community-based participatory research (CBPR) approach, which brings together scientists and community representatives.

Methods: This study was approved by the UNT Health Science Center IRB. Women residing in South Dallas were recruited for the intervention, and West Dallas was chosen as the control group. In addition to residence in one of these two communities, eligibility criteria included age 40 and older, English-speaking, and no personal history of cancer. Participants were recruited through community partnerships, posting flyers throughout the community in high-traffic areas, and door-to-door visits in the targeted areas. Participants in the control group received only written breast health educational materials. Intervention participants attended 8 weekly sessions that included written educational materials, cooking demonstrations and discussions with clinicians from the Dallas/Fort Worth area. All study participants completed a one-hour survey at baseline and 4 months later to assess the outcome variables as well as a variety of possible intervening variables.

Results: A total of 59 women were enrolled in the intervention and 60 in the control group. Retention for the 8-week intervention was 71 %. After controlling for baseline mammography status, women in the intervention group were 10.4 times more likely (95% CI: 2.9-36.4) to report having had a screening mammogram in the last year compared to the control group. Intervention participants demonstrated statistically significantly higher rates of breast self examination (OR: 3.0,95% CI: 1.0-8.6) and breast cancer knowledge (p=.003). Conclusion: Lessons learned from this study can be used to create sustainable cancer disparity reduction models that can be replicated in similar communities across the United States.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B2.
Abstract B24: When promotores and advanced technology meet: A qualitative analysis of promotores’ use of advanced technologies to increase colorectal cancer screening among South Texas Latinos
Authors: Sarah Arvey R. , Fernandez Maria E. , Bartholomew L. Kay
Published: December 2010

Advanced multimedia technologies can be used to tailor health messages, but promotores (lay health workers for Spanish speakers) rarely use these tools. Health messages intended to increase colorectal cancer screening among medically underserved Latinos in South Texas were delivered by promotores using a “usual practice” modality (flipchart and video) or a tailored, interactive modality via a computer. Using ethnographic methods, we observed promotor training and promotor delivery of the intervention, and conducted semi-structured, open-ended interviews with five promotores to assess the differences between the two technological modalities, and benefits and challenges of each. Findings reveal crosscutting benefits of the two modalities relating to cultural fit, as well as differing ways the two modalities acted as an aid or a burden to promotor/participant communication. This study makes significant contribution to the understudied area of combining the effective health promotion strategy of lay health workers with advanced multimedia technologies to increase cancer screening among Latinos.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B24.
Abstract B39: Administrative tools to promote cancer health disparities research partnerships
Authors: O'Connell Mary A. , Thompson Beti , Loest Helena , Anderson Jennifer
Published: December 2010

For the past eight years New Mexico State University (NMSU) a minority-serving institution, and the Fred Hutchinson Cancer Research Center (FHCRC), a comprehensive cancer center, have increased the cancer research, training and outreach programs at NMSU through partnership activities. The institutional differences in missions, values and cultures presented challenges that were overcome by proactive planning, administrative energy and committees with bi-institutional representation. A number of surveys, handbooks, guidelines and policy statements were developed and used by the administrative team and committees that would be useful as templates or guides to other groups developing networks or partnerships that involve multiple organizations. The success of the partnership is documented in part by the publications written and subsequent grants awarded by the partnering scientists; as well as the number of students trained and their career paths in cancer research. These data will be presented chronologically. To provide the administrative tools that facilitated these activities, we have created a web portal from which these materials can be downloaded (http://cancer.nmsu.edu/). Examples of documents available in pdf format will be presented, these include (1) materials for local workshops on cancer health disparities; (2) surveys for student tracking and surveys for pre and post knowledge tests; (3) the career development templates for proposals from junior investigators, and the evaluation forms for use by the mentoring committee to monitor junior investigators progress; (4) the scoring sheets for use by the proposal reviewers; (5) conflict resolution policy for partnership projects; and (6) handbooks for student training.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B39.
Abstract B42: Short-term cancer research experiences for medical students: Goals and outcomes
Authors: Bhatt Ananta , Cho May , Beech Derrick , Marshall Dana
Published: December 2010

Over the last five years, we have implemented an NIH-R25-funded program that exposes minority medical students to cancer research. Our goals are to increase awareness of our medical students in regards to the various research opportunities available in cancer research and to access how this program has impacted their medical education and future goals. Through the students evaluation and documentation we gained an understanding of 1) overall evaluation of the program and its strengths and weaknesses, 2) impact of this program in the students residency selection, and 3) impact of this program on their choice of a career, both clinical and research, in the field of oncology. The R25 has been successful in increasing the number of minority students who participate in cancer research, present their research at regional and national meetings, and publish articles in peer reviewed medical journals. Overall, the experiences of the students in this program suggest that this program has been a positive part of their medical education. This program provides minority students at Meharry Medical College an opportunity to learn and participate in cancer research and attracts trainees to cancer research. The true success of this program will be determined in future after following the students to see if the experiences from this program impacted their career choice in cancer research.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B42.
Abstract B43: Assessment of an educational video and brochure in four languages: Cantonese, Hmong, Vietnamese, and English for biospecimen contributions
Authors: Dang Julie H. T. , Chen Moon S.
Published: December 2010

Background: Racially specific biospecimens increase the likelihood of developing personalized treatment approaches for cancer patients in comparison to utilizing biospecimens that may have originated from individuals of a different race than the patient. Thus increasing the proportion of biospecimens from Asian Americans would increase the likelihood of having biospecimens that may be more applicable to cancer treatments for Asian American cancer patients. We have not found any reliable data on the proportion of biospecimens derived from Asian Americans in any database due to a variety of factors. However, we assume that the proportion is relatively low. Therefore to increase contributions among Asian Americans, particularly for English-limited patients, we are developing a video and accompanying brochure in Cantonese, Hmong, Vietnamese and English for Asian Americans that explain the need for biospecimens and recruit them to donate biospecimens for cancer research.

Objectives: To test the feasibility of an in-language biospecimen education video and brochure intervention to increase biospecimen contributions among Asian Americans

Methods: By mid-August, our educational video and brochure in Cantonese, Hmong, Vietnamese, and English will have been professionally produced. Our assumption is that respondents will use the language that they will be most comfortable in. Thus, respondents who view the video and ask for the brochure in one of the Asian language are presumed to be less acculturated than those who view the video and ask for the English language brochure. By mid-September, we shall have pilot-tested it with multiple Asian Americans both in a group and in individualized settings. In particular, Chinese, Hmong, and Vietnamese UC Davis Cancer Center patients undergoing cancer surgery will be given the educational video to view and the brochure to read prior to surgery and prior to receiving the biorespository consent form.

Results: We anticipate presenting data by language and report responses on the basis of the extent to which respondents learned more about biospecimens and whether their new knowledge about biospecimen would now predispose them to more likely contribute biospecimens. We shall report on the extent to which the educational materials increased knowledge and willingness to contribute biospecimens for research.

Conclusions: Increasing the proportion of Asian American biospecimens for cancer research will increase the likelihood of more personalized cancer therapies for Asian Americans. Our pilot study is among the first to empirically assess the potential of in-language video and brochures to increase biospecimen contributions by Asian Americans.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B43.
Abstract B44: GMaP/BMaP Region 3: Coming together to eliminate cancer disparities in the South and Puerto Rico
Authors: Meade Cathy , Scarinci Isabel , Muñoz-Antonia Teresita
Published: December 2010

Background: The Transdisciplinary Geographic Management Program (GMaP) and Minority Biospecimen/Biobanking Geographic Management Program (BMaP) for Region 3 is designed to develop a systematic and comprehensive strategy for building a state-of-the-art network for the support and efficient management of cancer health disparities research, training, and outreach in the five Southeastern states and Puerto Rico. The overall goal of the GMaP/BMaP-3 Network is to eliminate racial/ethnic cancer health disparities by identifying factors associated with such disparities, developing culturally-relevant approaches to address these factors, and disseminating evidence-based interventions across the cancer control continuum and across the continuum of the socio-ecological model. Specific to biobanking the ultimate goal of this network is to create unique, centralized, public resources for multi-ethnic biobanking/biospecimens. These goals are being accomplished in three phases: 1) network establishment, 3) needs/assets assessment, and 3) implementation plan.

Methods: We first established a working infrastructure for a GMaP/BMaP hub in the southeast United States and Puerto Rico as a collaborative partnership among the following institutions: H. L. Moffitt Cancer Center and Research Institute, University of Alabama at Birmingham Comprehensive Cancer Center, Tulane University, Xavier University of Louisiana, University of Mississippi, Tuskegee University, Morehouse School of Medicine, Emory University - Winship Cancer Center, and Ponce School of Medicine. Although the partners have worked closely together in all aspects of the project, we established specific cores in order to obtain an in-depth examination of specific areas in cancer disparities: clinical trials, advanced/emerging technologies, biomedical informatics, communication/dissemination, and evaluation. Given the importance of biospecimen/biobanking (BMaP), additional cores were established specific to this topic: collection, processing, storage and analysis of biospecimen; community and sociocultural beliefs; ethical, legal, and policy. Once the network was established, we designed a comprehensive needs/assets assessment of current strengths, weaknesses, capabilities, needs and interest in cancer health disparities in our participating institutions, CRCHD programs, and targeted communities with regard to research, training, and infrastructure development.

Results: A draft of the Comprehensive Assessment Tool (CAT) specific to our region has being developed through a participatory and methodic process with active involvement of all partnering institutions.

Conclusions: The data obtained from the needs assessment will inform the planning, nature, and extent of activities associated with the development of an operational plan to prioritize cancer research and biobanking activities in the Southeast US and PR.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B44.
Abstract B47: Potential role for RNF8 in breast cancer development
Authors: Anduro-Corona Ivan , Thompson Patricia , Buckmeier Julie , Martínez María Elena , Gutiérrez-Millán Luis Enrique
Published: December 2010

Background: Women of Mexican descent have a higher mortality and higher proportion of triple negative or basal-like breast cancers with BRCA like features and a higher population burden of BRCA mutations. Basal-like breast cancer subtype is associated with an elevated Ki67 index and extensive genomic instability. This increase in the Ki67 index indicates cell proliferation and perhaps greater cell DNA damage. In another report it was shown that knockdown of ring finger 8 (RNF8), an E3 ubiquitin-protein ligase, by siRNA inhibited focus formation at double strand break sites suggesting that RNF8 is an important regulator of the DNA repair system. We hypothesized that loss of RNF8 would be associated with more aggressive tumors such as those having high Ki67 levels. We are investigating the hypothesis that RNF8 is a tumor suppressor gene and acts as a novel regulatory protein of BRCA1 expression in human breast cancers.

Methods: We tested whether 37 formalin fixed paraffin embedded human breast cancers taken from a population of Mexican women enriched for basal-like cancers show altered RNF8 and Ki67 mRNA expression compared to median expression as reference value.

Results: Copy number differences in tumors for Ki67 and RNF8 mRNA were observed. The average differences in copy number for Ki67 between low and high expressing tumors was 8.8 fold and for RNF8 the average copy number differences between high and low expressors were 5.5 fold. When we compared the relationship between RNF8 and Ki67 expression within individual tumors, RNF8 expression was positively associated with Ki67 gene expression (p=0.04). Tumors that were high RNF8 were significantly more likely to also be high for Ki67. We found a non-significant but similar direction between RNF8 and cyclin B1 (p=0.08) but no relationship between RFN8 and cyclin D1 gene expression (p=0.318). This suggests that RNF8 is overexpressed in the tumors that are undergoing high mitoses.

Conclusion: This is the first report demonstrating differential expression of RNF8 in a series of human breast cancers and a positive association between Ki67 and RNF8 levels. This finding is counter to our hypothesis that RNF8 acts as a tumor suppressor and that we would observe loss of gene expression. Interestingly, a recent study found that among BRCA deficient backgrounds, the involvement of an alternative DNA repair pathway that is prone to more mistakes involving p53 binding protein (53BP1), which interacts with RNF8 in cells, modifies susceptibility of the BRCA1 deficient background to carcinogenesis. Our findings may suggest that among some breast tumors overexpression of this altered DNA repair pathway including activation of RNF8 made contribute to the genomic instability in more aggressive tumors. Additional studies to assess the relationship between 53BP1 and RNF8 in these tumors are ongoing.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B47.
Abstract B48: Do the gut flora play a role in the high incidence of colon cancer in African Americans?
Authors: Brim Hassan , Lee Edward , Zoetendal Erwin , Nelson Karen , Torralba Mannolito , Smoot Duane , Ashktorab Hassan , Sears Cynthia
Published: December 2010

Colonic adenomatous polyps are common tumors occurring in 50% of Western populations with 10% risk of malignant progression. To date, the environmental exposures proposed to promote the development of colorectal cancer (CRC) have been primarily dietary agents. However, the local environment to which the colonic mucosa is exposed is created by the bacterial microbiota of the colon and their metabolic products that include toxins. African Americans are known to have a higher incidence of colon cancer than other groups.

We analyzed the gut flora from African Americans patients by both 16S rDNA sequencing and HIT (Human Intestinal Tract) Chip. Our findings reflected a high prevalence of Bacteroidetes and Clostridia groups with the Bacteroidetes slightly more represented in patients with colon polyps than healthy ones. While Bifidobacteria were not detected at all in all samples, Lactobacilliwere present at a very low frequency. Both bacteria are referred to as “good bacteria” and are generally associated with healthy colon. Helicobacter bacteria, associated with gastric cancer, were also detected in all analysed samples. Bacteroides fragilis and relatives were present in all samples at a high frequency. It is noteworthy that an enterotoxigenic Bacteroides fragilis have been found to trigger colon polyps formation in Min mice through a pSTAT3 pathway. A tissue microarray immunohistochemistry experiment on colon adenoma and matched normals revealed a strong expression of pSTAT3 both in colonic epithelial cells and in colonic immune cells in adenoma samples but not as much in normal ones. These findings highlight the presence of a possible ETBF-like induction mechanism in the analysed samples.

Enzyme immunoassay for the detection of antibodies against ETBF toxin would confirm such findings and a metagenomic analysis of the analysed samples would shed light on predominant bacterial functions in adenoma patients that might play a role in colon oncogenic transformation in this population.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B48.
Abstract B50: Telomerase expression is upregulated in response to severe oxidative stress
Authors: Uzamere Theodor U.
Published: December 2010

Overcoming cancer health disparities is one of the best opportunities available for lessening the burden of cancer. Telomerase is an enzyme predominantly associated with its ability to extend the ends of chromosomes, or telomeres, and is expressed in 90% of all cancers. Recent findings suggest that telomerase has multiple cellular functions completely independent of its catalytic ability. Some of these functions help promote cell survival in response to severe oxidative stress which in turn should aid in the ongoing battle against cancer health disparities. Telomerase expression has been implicated in aiding a cell's response to double strand strand breaks in DNA, mitochondria dysfunction, inhibition of apoptosis, and the promotion of cell proliferation. The protein component of telomerase, TERT, is thought to specifically enhance cell viability in response to the hypoxic microenvironment of a tumor. These protective roles of TERT could be vital in promoting cell survival during severe hypoxia. Telomerase expression is upregulated by the kinase Akt, which is in turn induced by the neuregulin/ErbB signaling pathway. Neuregulin is a glycoprotein that is necessary for smooth muscle and neuronal development. Neuregulin activates the ErbB tyrosine kinase family, which promotes cell survival, proliferation, and differentiation. Recently, neuregulin has been shown to be upregulated in response to serve hypoxia, and may reduce the inflammation response to oxidative stress. The mechanism of neuregulin expression protection is unclear, though microarray data shows that neuregulin expression decreases the expression of several pro-inflammatory cytokines. Based on these facts, our hypothesis states that neuregulin can regulate the expression of telomerase during severe oxidative stress, and that telomerase expression promotes cell survival during hypoxia. The addition of physiologic levels of neuregulin was able to induce telomerase expression, indicating that telomerase activation could play an important role in the cellular response to oxidative stress.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B50.
Abstract B51: Neuregulin induces telomerase expression in response to oxidative stress
Authors: Uzamere Theodor , Butts DeMario , Sharif Wallace
Published: December 2010

Telomerase is an enzyme that can extend the ends of chromosomes and is aberrantly expressed in 90% of all cancers. Recent findings suggest that telomerase has cellular functions independent of its catalytic ability to elongate the telomere. Telomerase expression has been implicated in aiding cellular response to double strand breaks in DNA, to mitochondria dysfunction, inhibition of apoptosis, and the promotion of cell proliferation. The protein component of telomerase, TERT, can specifically enhance cell viability in response to the hypoxic microenvironment of a tumor. Telomerase expression is upregulated by the kinase Akt, which is induced by the neuregulin/ErbB signaling pathway. Neuregulin is a glycoprotein that is necessary for smooth muscle and neuronal development. Neuregulin activates the ErbB tyrosine kinase family, which promotes cell survival, proliferation, and differentiation. Recently, neuregulin has been shown to be upregulated in response to severe hypoxia, and may reduce the inflammation response to oxidative stress. The mechanism of neuregulin expression protection is unclear, though microarray data shows that neuregulin expression decreases the expression of several pro-inflammatory cytokines. We hypothesize that neuregulin can regulate the expression of telomerase during severe oxidative stress, and that telomerase expression promotes cell survival during hypoxia. We examined telomerase expression in differentiated rat neuroblastoma cell and observed a significant increase in telomerase expression in response to the addition of physiological levels of neuregulin. Surprisingly, treatment with the oxidizing agent diidopropyl flourosphophate (DFP) had no effect on telomerase expression in these cells. The neuregulin-mediated telomerase expression did confer a mild survival benefit in this cell line. These results could strengthen the link between neurodegeneration and cancer.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B51.
Abstract B59: A novel mechanism in tumor development and progression
Authors: Osman Mahasin A.
Published: December 2010

Cancer is a progressive disease that can culminate in acquisition of metastatic potential by tumor cells and directly contributes to patient mortality. An understanding of the involved genetic elements and their cellular networks offer an exceptional opportunity for defining potentially relevant and effective targets for improving cancer therapy. IQGAP1 is a widely conserved effector of CDC42 GTPase and has emerged as a potential oncogene associated with diverse human cancers, however, its role in tumor development and progression remains unclear. Here we discuss a novel mechanism by which IQGAP1 generates neoplastic lesions and promotes progression to metastasis.

Our work shows that IQGAP1 binds mTOR and regulates cell homeostasis. Expression of the N-terminal domain, which binds mTOR, enhances insulin secretion, enlarges the cell size and arrests cytokinesis whereas expression of the C-terminal domain that binds and activates CDC42GTPase, accelerates the cell cycle and decreases the cell size. Expression of full-length or the C-terminal domain also increases serine phosphorylation of IQGAP1 and generates transformed phenotypes that are sensitive to rapamycin and PI3K-Akt1 inhibitors.

These findings suggested that IQGAP1 serves as a phosphorylation-sensitive conformational switch to modulate cell proliferation. Indeed, treatment with EGF increases IQGAP1 phosphorylation and the phosphomimetic, but not the phosphodefective, mutant generates transformed phenotypes and promotes cell invasion. In response to EGF, IQGAP1 attenuates mTORC1 signaling and activates Akt1, which may provide an in vivo mechanism by which it generates neoplastic transformation and progression to metastasis. Thus our work has uncovered a novel pathway CDC42-IQGAP1 -mTORC1 -Akt1 in tumor development and progression that may yield new approaches for cancer detection and treatment.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B59.
Abstract B60: NR4A2: A novel therapeutic target in triple negative breast cancer
Authors: Williams Christopher C. , Llopis Shwan D.
Published: December 2010

Despite the lack of an increased rate of breast cancer occurrence among African American women, African American women suffer greater mortality due to breast cancer as compared with other ethnic groups. Recent studies suggest that the increase in mortality is likely multifactorial, however the elevated occurrence of triple negative (ER-/PR-/HER2-) breast cancer may be a key factor in decrease survival among African American women. Since the lack of ER and HER2 make these patients ineligible for hormonal therapy or Her2 targeted therapies such as trastuzumab, patients are often relegated to cytotoxic chemotherapeutic strategies. As such, it is imperative to identify therapeutic targets which can be exploited to design highly selective, less toxic regimens which are effective in treating triple negative breast cancer. The NR4A (NR4A1, NR4A2, and NR4A3) orphan nuclear receptors have the potential to serve as distinct, specific pharmacological targets which can directly affect apoptosis in triple negative breast cancer cells. Breast tumor microarrays demonstrate that NR4A2 is highly expressed in the nucleus of normal, but not malignant breast epithelial cells. shRNA-mediated silencing of NR4A2 in triple negative breast cancer cells leads to increased proliferation in vitro and in breast cancer xenograft models. In vitro studies also revealed that shRNA silencing of NR4A2 expresssion mediated partial resistance to doxorubicin, while overexpression of NR4A2 leads to cell cycle arrest. Additionally, gene expression arrays show that overexpression of NR4A2 induces expression of angiogenic factors, as well as causes suppression of markers associated epithelial-mesenchymal transition. Taken together, these studies suggest that NR4A2 is a viable pharmacological target in triple negative breast cancer. Targeting triple negative breast cancer may prove an effective means to address the disparity in survival rates of African American women as compared to other ethnicities.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B60.
Abstract B65: Targeted resequencing of the EphB2 gene in colorectal cancer for SNP discovery using next generation sequencing
Authors: Robbins Christiane M. , Harris Jake A. , Tembe Waibhav , Shamugam Vijayalakshmi , Kittles Rick A. , Ellis Nathan A. , Carpten John D.
Published: December 2010

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality in the United States. CRC is the third most common cause of deaths in the U. S. with the highest incidence observed in the African American (AA) population compared to other American populations. Our group was the first to implicate the EphB2 tyrosine kinase receptor as a tumor suppressor in prostate cancer (PC), where we reported somatic inactivating mutations occurring in 5%-10% of sporadic tumors. With its role in maintaining normal epithelial architecture and functional data suggestive of a tumor suppressor in both prostate and colon cancer.

Recent advances in next-generation sequencing (NGS) afford new opportunities for large scale SNP discovery using a targeted resequencing approach. Several methodologies have been developed for targeted resequencing. Among these methods is the RainDance picoliter massive single-plex PCR assay, which provides the capability to assess up to 10,000 independent amplicons in a single reaction. We designed a RainDance PCR assay containing 700 amplicons, encompassing the entire 225,000bp genomic region of the EphB2 gene. These individual pools of amplicons from each sample were then used as template for NGS and barcoded to generate pools of 16 unique individuals using the Life Technologies SOLiD version 3-Plus system. Utilizing this method we screened 20 colorectal cancer cases and 27 sporadic prostate cancer cases. Thus far we have identified both known and novel variants within the EphB2 gene region among of which are several common coding variants including the 2055A>T nonsense mutation (K1019X) in three of 10 female CRC cases. We will provide data on the number of novel and known single nucleotide polymorphisms (SNPs) for all CRC and PC cases as well as quality assessment and overall performance of the RainDance method and performance metrics for SOliD NGS along with a comparison of utilizing several different analyses pipelines to identify the novel and known SNPs. These data will provide us with unprecedented details of the genetic variation of the EphB2 gene in African Americans.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B65.
Abstract B71: Residential racial segregation and prostate cancer treatment decisions
Authors: Wells Kristen , Stukenborg George , Oliver M. Norman
Published: December 2010

Residential racial segregation, or the relative degree to which members of two or more racial groups are spatially distributed throughout a defined geographical area, is associated with the health status of individuals living in racially segregated communities. Despite pronounced racial disparities in prostate cancer incidence and mortality, no known study has investigated the association between racial residential segregation and prostate cancer post-diagnosis treatment. The objective of this study is to evaluate the independent effect of residential racial segregation as measured by the isolation index on prostate cancer treatment decisions. Incident prostate cancer cases among men living in metropolitan statistical areas that were reported to the SEER-Medicare linked database between 1995 and 2002 were identified. Differences between individual and area-level characteristics at varying degrees of residential segregation were statistically evaluated using Chi Square and Student's t tests and ANOVA. Hierarchical logistic regression models with MSA- level random effects were used to characterize the relationship between level of residential segregation and post-diagnosis prostate cancer treatment received. African American men living in metropolitan areas with high segregation were statistically significantly more likely to receive expectant management (OR=1.42, 95% CI= 1.09, 2.23) and were statistically significantly less likely to receive radiation therapy (OR=0.56, 95% CI=0.34, 0.93) compared to white men living in areas of low segregation. Black men living in metropolitan areas with high segregation were more likely to receive radical prostatectomy (OR=1.59, 95% CI= 0.57, 4.45) and hormone therapy (OR= 2.08, 95% CI=0.91, 4.77) than white men living in areas of low segregation, although these differences were not statistically significant. Researchers should continue to investigate the implications of access to care and healthcare utilization by various populations and their effect on prostate cancer treatment decisions.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B71.
Abstract B76: The effect of ethnicity on esophageal cancer survival in British Columbia, Canada
Authors: Bashash Morteza , Hislop Greg , Shah Amil , Le Nhu , Brooks-Wilson Angela , Bajdik Chris
Published: December 2010

Background: Esophageal cancer is one of the most lethal human malignancies. This study compares the survival of esophageal cancer patients among ethnic groups in British Columbia (BC), specifically Chinese, South Asians and Iranians.

Methods: Data was obtained from the population-based BC Cancer Registry for patients diagnosed with invasive esophageal cancer between 1984 and 2006. Complete follow-up information was available for all patients to 31 August 2007. The ethnicity of patients was determined according to their names and categorized as Chinese, South Asian, Iranian or Other. Cox proportional hazards regression analysis was used to estimate the effect of ethnicity adjusted for patient gender, patient age, disease histology, tumor location, disease stage and treatment.

Results: The survival of esophageal cancer patients was significantly different among ethnic groups when evaluated without adjusting for other variables (p=0.03), but not in the multivariate model (p=0.06). A significant survival difference was observed among ethnic groups only for non-metastatic disease (p=0.049). The results indicate that South Asians have better survival than the other groups.

Discussion: Ethnicity may represent underlying genetic factors that could affect survival. Such factors could influence host-tumor interactions by altering the tumor's etiology and therefore its chance of spreading. Host pharmacogenetic factors can also affect a patient's response to treatment. Differences in survival by ethnicity support the importance of ethnicity as a prognostic factor, and may provide clues for the future identification of genetic or lifestyle factors that underlie these differences.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B76.
Abstract B8: Research on HIV/AIDS-related cancers among racial/ethnic minority and underserved persons in the United States
Authors: Richardson Sandra F
Published: December 2010

Purpose: To develop a community based participatory research (CBPR) program that establishes an effective way to engage Africans in Zambia and underserved Alabama Black Belt communities in HIV awareness, stigma reduction, voluntary HIV testing and engagement in care, active and appropriate prevention and early detection of HIV-related malignancies, and proper treatment, when necessary.

Background: The Deep South Network for Cancer Control has trained over 800 community health advisors (CHAs) that have functioned to increase cancer awareness in their communities, leading to considerable improvement in breast and cervical cancer screening in the targeted communities. The UAB Center for Infectious Disease Research in Zambia (CIDRZ) has reached over 500,000 women for preventing mother-to-child transmission and has enrolled over 200,000 HIV patients into care. They screen over 1,000 women per month for cervical cancer. A major common issue in both programs is the stigma associated with HIV. This leads to unwillingness to be screened, continuous transmission of disease, and subsequent development of HIV-related malignancies.

Methodology: Bring the two communities together to learn from each other in order to develop an appropriate community based participatory research strategy to overcome the major issues. This would be accomplished by: (1) establishing an organizational infrastructure to form a foundational research program (2) conducting onsite meetings in the United States and Zambia to experience the unique attributes of each country (3) conducting a needs assessment to evaluate infrastructure addressing HIV testing and HIV-related cancer prevention, early detection and/or treatment at three levels: community, investigators and institution (4) developing a CBPR plan to insure underserved minorities in the Alabama Black Belt and Zambia receive appropriate HIV testing and HIV-related cancer prevention, early detection, and/or treatment.

Results: There were many lessons learned in Lusaka and in Alabama: 1) Peer educators play a vital role in outreach and support. Peer educators who are a part of the program, must be involved in support groups as well. 2) Peer educators have more impact when they are trained individuals. 3) Community ownership is important; have to find the passion in the community and have the ownership working from the inside out. 4) Education offered in the work place yields positive results. 5) Mass media dissemination has a great influence on the message being carried. 6) Targeted campaigns have proven beneficial. 7) Health fairs are widely received.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B8.
Abstract B85: Impact of patient/provider communications on quality of care for cancer
Authors: Khan Shahnaz , Colosia Ann D. , Peltz Gerson , Pohl Gerhardt , Liu Esther , Kaye James A.
Published: December 2010

Objectives: Quality of care for cancer could be impacted by a variety of factors. The objective of this study was to identify aspects of patient/provider communications that impact the quality of care for cancer patients in general.

Methods: A systematic literature review regarding perceptions of the quality of cancer care in the U.S. was conducted in PubMed, EMBASE and Cochrane Reviews for the last ten years, English only articles. Oncology medical subject heading (MESH) terms were cross-matched with quality of care MESH terms to obtain 875 abstracts. Of these, 140 publications were selected for full-article review based on defined inclusion/ exclusion criteria.

Results: Most of the articles on patient/physician communications and quality of care were for breast cancer. The amount of information patients receive regarding their cancer and their communications with providers affects their perceptions of quality of cancer care. Women with breast cancer who reported high levels of surgeon-initiated communication were more likely to be satisfied with their care than women receiving low-levels of communications. Women who were provided with a nurse case manager had more positive perception regarding their treatment choices and quality of care. Poor communication and lack of information are often cited as factors affecting service quality. While providers may consider technically proficient care to mean quality care, patients with cancer define quality care as care that comes with good communication, provision of adequate information, respect, and attention.

Conclusions: Communications with providers and provision of adequate information are important aspects of quality of cancer care for patients with cancer. These findings may be more pronounced in circumstances where diversity issues are relevant.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B85.