bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A105: Application of national guidelines diminishes racial disparities in end-of-life cancer care
Authors: Austin Laura K. , Pendleton Delinda , Zhu Fang , Engstrom Paul , Levy Michael , Swaby Ramona F.
Published: June 2012

Introduction: There are known racial disparities in cancer mortality among African American (AA) patients with shorter median survival rates compared to white patients. Utilizing evidence based clinical guidelines allows for equitable treatment of all patients and may eliminate disparities. The goal of this study was to determine whether AA patients were referred to hospice earlier in their treatment course at a tertiary academic cancer center that routinely utilizes nationally recognized treatment guidelines (i.e. – National Comprehensive Cancer Center Network, NCCN).

Methods: We retrospectively analyzed 315 charts of patients referred for hospice during 2008–2009. Subjects identified as either AA or Caucasian were analyzed by race, age and socioeconomic category. Subjects residing in geographic neighborhoods corresponding to postal zip codes with median incomes of either > or ≤ $50,000 were used as a surrogate for socioeconomic status. Charts were reviewed to determine how many lines of chemotherapy were administered before hospice referral. Patients were excluded if they were referred to hospice without receiving chemotherapy. Age, number of chemotherapy regimens and socioeconomic status were compared using Wilcoxon rank-sum test within each race. The overall number of lines of chemotherapy stratified by race was compared using Van Elteren's Test. All categorical variables were summarized by year and race and compared using Fisher's exact test.

Results: Patient characteristics and outcomes are as listed in the table below. There was no significant difference between the average number of lines of chemotherapy administered to AA or Caucasian patients, respectively (2.92 vs 2.62; p=0.026), and no racial difference in the percentage of patients referred for hospice discussion prior to hospice transfer [AA (92.2%) Caucasian (83.3%); p=0.36). Similarly, adherence to NCCN treatment guidelines was similar between races [AA (89.1%) Caucasian (93.1%); p=0.36]. AA patients were more likely to reside in a zip code with a lower median income (p<0.001). Interestingly, lower income Caucasian patients were statistically found to have been treated with more lines of chemotherapy prior to hospice, (2.81 compared to 2.39; p=0.04).

Conclusions: In this retrospective single institution analysis, there was no evidence that AA patients or patients from lower median incomes were referred to hospice earlier than white patients or patients with higher median incomes. These results are encouraging and may be partially attributable to the use of evidence based NCCN treatment guidelines, suggesting that applying such guidelines to all patients help to eliminate racial bias and disparities in cancer care.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A105.
Abstract A2: Region 4 NCI CRCHD BMaP: A team science approach towards a multistate network to reduce cancer health disparities
Authors: O'Connell Mary A. , Vilchis Leticia O. , Oushy Mai H. , Ramirez Amelie G. , Gallion Kipling J. , Holden Alan
Published: June 2012

Background/Objectives: NCI CRCHD Region 4 BMaP (Arizona, Colorado, Oklahoma, New Mexico and Texas) was initiated in 2009. The overall goal is achieving measureable reductions in racial cancer health disparities through developing regional networks where resources can be pooled to facilitate team science approaches to cancer health disparity reduction.

Methods: We established a regional hub infrastructure with specific cores: administration, training, bioinformatics, biospecimen/biobanking, clinical trials, community translation, emerging technologies, and ethical-legal-policy issues. Three methods, a group meeting and two survey tools were employed to identify regional resources. The NCI-developed Readiness Assessment Tool (RAT) collected data on cores; the “Face-to-Face” gathering provided for a SWOT analysis in cancer health disparities among Region 4 stakeholders. The online Comprehensive Needs Assessment (CNA) survey identified institutional-level characteristics necessary to develop a regional implementation plan.

Results: 100% complete response for RAT and CNA surveys. Few reported significant needs although many reported significant institutional deficiencies in bioinformatics, biospecimen/biobanking, clinical trials, and emerging technologies. Primary diseases of interest include breast and colorectal cancers. In Region 4, few CRCHD funded investigators collected biospecimens in their research programs; and all members reported strong training programs. The Face-to-Face meeting strengthened existing partnerships and increased collaboration while providing attendees a regional overview of strengths, weaknesses, opportunities, and threats.

Implications/Next Steps: Regional networks of health disparities researchers are already leverging resources to reduce cancer health disparities among minorities in the region. The GMaP/BmaP network provided contacts to leverage CHEs in the region. The program is investigating methods to create a region-wide virtual biorepository, with descriptions of biospecimens collected in research program by Region 4 PIs. Such a virtual biorepository database would be linked with other regioanl BMaP databases that are developed. In addition, Region 4 implementation plan includes creating bioethics training tools for biomedical research on US minority populations. Training materials to be developed would address missing bioethical topics on health disparities issues with an emphasis on Native Americans and Hispanic Populations, and within the topics of biospecimen collection and clinical trial participation. This aims at creating career opportunities in bioethics for students and junior investigators at minority serving institutions.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A2.
Abstract A33: African American men's perceptions of the informed decision-making process for prostate cancer screening: Implications for design and development
Authors: Rivers Brian M. , August Euna M. , Schenck April , Jackson Myron , Scian Joanna , Dimaggio Angela , Quinn Gwen
Published: June 2012

Introduction: Although prostate cancer mortality rates are on the decline, rates in African American men remain more than twice as high as those in white men. Men at risk for prostate cancer are encouraged to utilize informed decision making (IDM) to determine the most appropriate strategy for screening and prevention. However, multiple barriers exist in the provision of culturally and linguistically appropriate IDM models on prostate cancer for African American men, including mistrust of the health system, fear of cancer, and concerns about discrimination and racism. Multimedia approaches have been determined to be an effective means for the dissemination of culturally and linguistically appropriate IDM models for African Americans that minimize barriers within the community.

Methods: Focus groups were conducted with African American men in the Tampa Bay area to determine core elements for the design of a video-based patient decision aid for prostate cancer screening. Lay health advisors from the community recruited African American men to participate in this formative research. The inclusion criteria were: African American men; aged 40 to 70 years; and no diagnosis of prostate cancer or any other type of cancer. The focus groups were transcribed verbatim and analyzed using a combination of content analysis and the constant comparison method with Atlas.ti software.

Results: A total of 18 African American men, ranging in age from 41 to 65 years, were recruited (mean age=48.5 years). Overall, men had limited knowledge regarding prostate cancer, and slightly more than one-third (38.9%) of the men had previously been screened for prostate cancer. Multiple themes emerged through the conduct of focus groups, including the influence of cultural beliefs in screening, the need for more information on risk and protective factors for prostate cancer, the involvement of spouses and family members in decision-making, and the importance of culturally-appropriate educators, advocates, and role models.

Conclusions: Overall, there is a lack of information regarding prostate cancer among African American men. Cultural perceptions and beliefs play a critical role in the determination of screening practices in this community. Patient decision aids on prostate cancer for African American men require the utilization of African American health professionals and peers as purveyors of information. Furthermore, messaging should be tailored for African American men, as well as their spouses and families, to aid in the determination of appropriate prevention and screening strategies. These findings will assist in the design and development of culturally and linguistically appropriate educational resources and interventions on prostate cancer for the African American community.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A33.
Abstract A49: Multifunctional nanocarriers against cervical cancer
Authors: Saunders Mary R. , Olivos David J. , Lim Ryan G. , Berti Lorenzo , Lam Kit S.
Published: June 2012

Cervical cancer accounts for 500,000 new cases and 250,000 deaths in women worldwide. In low-income countries, cervical cancer is the most common cause of cancer-related deaths among women. Novel approaches for the early detection and aggressive treatment of cervical cancer are urgently needed to increase the survival rates. To this end, a promising strategy that might improve the specificity of current diagnostic and therapeutic agents is the development of drugs or contrast agents targeting glycans, polysaccarides decorating normal and cancerous cells that provide a unique fingerprint on the cell surface. Tumor glycans are important in regulating pivotal events during the development and progression of cancer. Changes in their sequence and structure are known to be responsible for cell proliferation, invasion, angiogenesis, and metastasis. Malignant transformation of cervical cells is accompanied by the expression of specific glycans that are absent on normal uterine cervix cells. Peptide-based ligands specific for these cervical cancer glycans have been discovered, and their use as tumor-homing agents for diagnostics and therapeutic purposes has been explored in xenograph models. We have currently developed an innovative drug delivery vehicle for the simultaneous and highly specific imaging and treatment of cervical cancer. To take full advantage of the enhanced permeability and retention effect (EPR) of the nanocarriers and to have deep penetration inside the tumor mass, we have developed a telodendrimer system, comprised of clusters of oligomeric cholic acids (CA) linked to a polyethylene glycol (PEG) chain which self-assemble within an aqueous environment with tunable sizes and efficient drug loading capacity. This vehicle consists of a nanocarrier loaded with the powerful anticancer drug, doxorubicin, and decorated with cervical cancer specific ligands targeting cell surface glycans. Thanks to the presence of the targeting ligands, the nanocarriers carry the otherwise non-selective drug specifically into the targeted cancer cells leading to release of anticancer drug only where needed. Because of the lower doses and the relatively low cost of the nanoparticle employed as drug carriers, we envision that this technology will be amendable for clinical translation and will be a powerful therapeutic tool to address the needs and disparities typical of less developed countries.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A49.
Abstract A88: Ancestry informative markers associated with prostate cancer in African Americans
Authors: Wilson Bradford D. , Ricks-Santi Luisel J. , Mason Tshela , Apprey Victor , Bonney George , Dunston Georgia M. , Kittles Rick A.
Published: June 2012

Purpose: Prostate cancer (Pca) is the most common cancer in US males. African American men have higher incidence and mortality rates than do their European American counterparts. Five single nucleotide polymorphisms (SNPs) were found to be associated with Pca after analyzing data from a Pca mapping by admixture linkage disequilibrium (MALD) study using several different genetic models. The SNPs genotyped have significant allele frequency differences between African Americans and European Americans and are referred to as ancestry informative markers (AIMs). We tested the hypothesis that AIM haplotypes were also associated with Pca risk.

Design Methods: AIM haplotypes were inferred for 98 Pca patients and 140 controls. Binary logistic regression was used to test haplotypes for association with Pca.

Results: We found that haplotypes 5 “GTCCC,” 9 “ATTCT,” and 11 “ACCCC” were associated with Pca risk (OR = 3.97 95% CI: 1.68–9.47, p = 0.0017; OR = 7.17 95% CI: 2.33–20.05, p = 0.0006; OR = 3.68 95% CI: 1.57–8.62, p = 0.0027, respectively). After adjusting for age and ancestry all three haplotypes remained associated with Pca (OR = 3.62 95% CI: 1.42–9.21, p = 0.0070; OR = 7.89 95% CI: 2.36–26.31, p = 0.0008; OR = 4.34 95% CI: 1.75–10.78, p = 0.0016, respectively).

We show that AIM haplotypes are associated with PCa risk. This study also demonstrates the use of a simple model to test for the additive or multiplicative effects of SNPs weakly associated individually.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A88.
Abstract A93: Correlates of total testosterone and testosterone deficiency in African American men
Authors: Murphy Adam B. , Nyame Yaw , Kelley Brian , Ahaghotu Chiledum A. , Kittles Rick A.
Published: June 2012

Introduction: Elevated serum total testosterone (TT) levels have been associated with increased prostate cancer incidence and mortality faced by African American (AA) men. Testosterone deficiency (TD) is linked to several health outcomes including increased cancer and all-cause mortality. Several studies have examined the relationships between TT levels and biochemical and environmental factors, but few have examined these correlates in AA men. This study evaluated TT levels, TD and their correlates in AA men.

Methods: Blood samples were collected from 191 controls recruited from 2000–2003 from the Urology clinic at the Howard University Hospital, along with demographic data, reported alcohol use, and BMI. Measurements of testosterone (total and free), prostate specific antigen (PSA), triglycerides (TG), total cholesterol, HDL, VLDL, LDL, IGF1 and IGFBP3 levels were obtained from the blood. Percentage west African genetic ancestry was determined using a panel of 100 ancestry informative markers.

Results: On linear regression, age, HDL, LDL and IGFBP3 levels were associated with TT levels (p< 0.05). However, TT levels were not associated with degree of West African ancestry (p = 0.52). Using multivariate analysis, TD deficiency (TT < 300 ng/dL) was positively associated with TG levels (p < 0.05), alcohol use and elevated BMI (p = 0.018 for both). The highest quartile BMI (BMI > 31) was at 2.48 times higher risk for TD than the lowest quartile (< 25). The correlates of TT levels and risk factors for TD in AA men are similar to the established risk factors in European American men.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A93.
Abstract A99: Racial disparities in receipt of prostatectomy from a high-volume urologist: The role of diagnosing urologists and doctor changing
Authors: Pollack Craig Evan , Bekelman Justin , Epstein Andrew J. , Liao KJ , Wong Yu-Ning , Armstrong Katrina
Published: June 2012

Background: Though patients who receive surgery from high-volume surgeons tend to have better outcomes, black patients are less likely to receive surgery from high-volume surgeons.

Objective: Among men with localized prostate cancer, we examined whether disparities in use of high-volume urologists resulted from racial differences in patients being diagnosed by high-volume urologists and/or changing to highvolume urologists for surgery.

Research Design: We performed a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) Medicare data. 26,058 black and white men who were diagnosed with localized prostate cancer from 1995 to 2005 and who underwent prostatectomy were included. Patients were linked to both a diagnosing urologist (who submitted a claim nearest the date of diagnosis) and a treating urologist (who performed the surgery). Logistic regression models were used to examine racial differences in diagnosis and treatment by a high versus low volume urologist. Among patients who were diagnosed by a low-volume urologist, multinomial logistic regression models with robust standard errors were used to examine whether patients: (a) did not change physicians (baseline category), (b) changed to a low-volume treating urologist, and (c) changed to a high-volume treating urologist.

Results: Black men were as likely as white men to be diagnosed by a high-volume urologist; however, they were significantly less likely than white men to be treated by a highvolume urologist (Odds ratio 0.76, 95% Confidence Interval [CI] 0.67, 0.87). For men diagnosed by a low-volume urologist, 45.0% changed urologists for their surgery. Black men were less likely to change urologists overall (35.3% versus 45%, p<0.001) and less likely to change to a high-volume urologist than white men (9.1% versus 14.3%, p<0.001). These racial differences in changing providers remained significant in multinomial regression analyses. Racial differences appeared to reflect black and white patients tending to be diagnosed by different urologists (between-provider effects, RRR 0.37, 95%CI 0.18, 0.74) as well as having different rates of changing after being diagnosed by the same urologists (within-provider effects, RRR 0.79, 95%CI 0.66, 0.94).

Conclusions: Lower rates of changing to high-volume urologists for surgery among black men contribute to racial disparities in treatment by high-volume surgeons. The results suggest that interventions that attempt to reduce disparities in access to high-volume surgeons will require a deeper understanding of the specific pathways through which patients come to receive surgical care.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A99.
Abstract B107: Combination therapy of kidney cancer using bortezomib and natural killer (NK) cell transfer
Authors: Pellom Samuel Troy , Malhotra Anshu , Shanker Anil
Published: June 2012

Kidney cancer is a malignant tumor that accounts for about two percent of all cancers in the United States. African American men and women account for a higher incidence rate of kidney cancer compared to other races. The higher rate of failure of current immunotherapeutic strategies is attributed to the immunosuppressive effects as well as modification of the immune-regulatory circuits brought about by cancers. With the aim of enhancing immune mechanisms against kidney cancer, we undertook a combinatorial approach to reveal the therapeutic potential of adoptive cell transfer regimens using mouse models in conjunction with molecular targeting drugs that sensitize kidney tumor cell-death. The proteasome inhibitor, bortezomib, selectively sensitizes kidney tumor cells to apoptosis by activating caspase-8 in the extrinsic apoptosis pathway. Moreover, our studies thus far have revealed that bortezomib can also enhance natural killer (NK) cell antitumor function. We observed that bortezomib upregulates Fas and NK cell activating receptor NKG2D ligand Rae1-on renal cancer Renca cells in vivo. Moreover, preliminary observations suggest that bortezomib can be combined with adoptive NK cell transfer to provide greater therapeutic benefits with little adverse effects in vivo. These new data predict the potential of combining adoptive NK cell transfer regimens with bortezomib-induced sensitization of kidney tumor cells to induce apoptosis. Such a combinatorial approach of NK cell transfer coupled with bortezomib treatment would have dual effects by sensitizing tumor cells to cell death and improve NK cell effector functions. This could prevent tumor metastasis by eliminating tumor escape variants and significantly benefit tumor immunotherapy efforts in kidney cancer.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B107.
Abstract B21: Factors associated with mammography use among foreign-born women and changes over time
Authors: Yao Nengliang (Aaron) , Hillemeier Marianne
Published: June 2012

Background: Disparities in mammography screening remain a problem for immigrant women, while the foreign-born population has been increasing for decades in the United States. Recent studies indicate that factors associated with mammography use may have changed. Little research has been done to analyze the changing patterns of factors associated with mammography use among immigrant women. Purpose: To address these knowledge gaps, this study (1) compares age-adjusted mammography rates among immigrants by certain characteristics in 2000 and 2008; and (2) examines the factors associated with recent mammography use among immigrant women at these two time points.

Methods: National Health Interview Survey 2000 and 2008 data were used to calculate population-based descriptive statistics adjusted for survey design. Multivariate logistic regressions were used to determine factors associated with recent mammography use among immigrant women.

Results: The mammography rates rose from 60.18% in 2000 to 65.47% in 2008 among foreign-born women. Immigrants having poor access to health care, those who recently immigrated, younger immigrants, and those with low education had the lowest mammography rates at both time points. After adjusting for covariates, lack of access to health care persistently contributes to the lower percentage of mammography screening among immigrants. Longer residency in the U.S. was associated with a higher chance of receiving mammography among immigrants in 2000 but not in 2008. In contrast, age 50–64 compared to age 65 or older was associated with a higher chance of receiving mammography among immigrants in 2008 but not in 2000.

Conclusion: Mammography rates have improved over time among immigrant women and some disparities are decreasing, however, lack of health care access remains an important barrier to breast cancer screening for this population.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B21.
Abstract B53: Patterns of meat intake and risk of prostate cancer among African-Americans in a large prospective cohort of men
Authors: Major Jacqueline M. , Cross Amanda J. , Graubard Barry I. , Sinha Rashmi
Published: June 2012

Objective: Given the large racial differences in prostate cancer risk, further investigation of diet and prostate cancer is warranted among high-risk groups. The purpose of this study was to examine the association between type of meat intake and prostate cancer risk among African-American men.

Methods: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995–1996) data from African-American participants, ages 50–71 years. Incident prostate cancer cases (n=1,089) were identified through 2006. Dietary and risk factor data were ascertained by questionnaires administered at baseline. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) within intake quantiles.

Results: Neither white nor processed meat intake was associated with prostate cancer, regardless of meat cooking method. Red meats cooked at high temperatures were associated with an increased risk of prostate cancer (HR=1.18, 95%CI=1.00-1.38 and HR=1.22, 95%CI=1.03-1.44, for the upper two intake tertiles). Intake of the heterocyclic amine (HCA), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx) was positively associated with prostate cancer (HR=1.30; 95% CI=1.05-1.61, P=0.02). No associations were observed for intake of other HCAs.

Conclusion: Red meats cooked at high temperatures were positively associated with prostate cancer risk among African-American men. Further studies are needed to replicate these findings.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B53.
Abstract B54: Biological and environmental predictors of vitamin D status in African American and European American men in Chicago
Authors: Murphy Adam B. , Nyame Yaw , Kelley Brian , Smith Demetria J. , Castaneda Lauren , Minaya Katherine , Hollowell Courtney M.P. , Kittles Rick A.
Published: June 2012

Introduction: Vitamin D deficiency is epidemiologically linked to prostate, breast and colon cancer. African American (AA) men have increased risk relative to European American (EA) men, but few studies evaluate vitamin D status in AA men. We evaluate the biological and environmental predictors of vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet radiation (UVR) environment.

Methods: Blood samples were collected from 492 men, age 40–79, from urology clinics at three hospitals in Chicago, along with demographic and medical information, BMI, and skin melanin content using a portable narrow-band reflectometer. Vitamin D intake (dietary and supplemental) and UVR exposure were assessed using validated questionnaires.

Results: Mean and median 25-OH D levels (normal: 30–80 ng/ml) were 17.2 and 16.0 ng/ml in AA men and 26.0 and 25.0 ng/ml in EA men, respectively (p < 0.01). Also, 93% of AA vs. 69.7% of EA men (OR = 1.33) were vitamin D deficient (P < 0.01). AA status (p = 0.04), age, and BMI (p < 0.01) were positively correlated with vitamin D deficiency, while vitamin D supplement use and sun exposure were negatively correlated (p < 0.05). Our multivariate analysis revealed that AA status, BMI, and lack of vitamin D supplementation were negatively associated with 25-OH D level (p < 0.05).

Conclusion: Sunlight exposure, BMI and vitamin D supplementation are associated with vitamin D deficiency and represent modifiable risk factors. Race and sunlight exposure should be taken into account for recommended daily allowances for vitamin D intake.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B54.
Abstract B58: Promoting healthy lifestyle and cancer awareness through a Pacific Islander fitness day
Authors: Lepule Jonathan “Tana” , Aina Sefa
Published: June 2012

Chronic disease is the leading cause of death for Pacific Islanders in the U.S., who number over 1.1 million and suffer from enormous health disparities. Obesity prevention and reduction are primary concerns among Pacific Islanders, yet there is little information on the physical activity and nutrition knowledge, attitudes, beliefs, and behaviors in the population. For instance, one of five Pacific Islander youth in the U.S. is obese. Western culture and dietary habits have influenced PI lifestyles. Among Samoans, obesity prevalence ranged from 33–75% in males and 46–80% in females in four different islands.

The majority of Pacific Islanders in California live in Southern California, and in May 2011 a unique effort was initiated promoting physical activity and healthy eating tailored after Michelle Obama's “Let's Move” campaign. Pacific Islander Fitness Day was an outreach event in collaboration with numerous entities (including the White House Initiative on Asian Americans and Pacific) to increase awareness for health checkups, cancer screening, physical activity, and nutrition among those ages 5 to 73. This event comprised: speakers from community leaders, physical activity stations lead by NHPI athletes, a Health Village with resources promoting health screenings and a Diet and Healthy Food Village with information on healthy food choices and preparing cultural food with health in mind.

A total of 221 participants completed a brief needs assessment survey. Factors influencing their physical activity and eating behaviors included cost of food (p=0.024), health of food (p=0.036), and exercising more than three times per week (p=0.000). These results will better inform those serving Pacific Islanders by addressing cancer health disparities through physical activity and the prevention of cancer and comorbid diseases.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B58.
Abstract B63: ESR1 variants are not associated with breast cancer in African American women
Authors: Ochs-Balcom Heather M. , Sucheston Lara , Liu Song , Hutter Carolyn , Young Alicia , Peters Ulrike , Chlebowski Rowan , Wactawski-Wende Jean
Published: June 2012

The estrogen receptor alpha (ESR1) gene is a candidate gene for breast cancer due to the ligand-activated transcription factor it encodes. The Breast Cancer Association Consortium (BCAC) identified an association of haplotype tagging SNPs in intron 4 of ESR1 and breast cancer risk in 21 European studies that include 53,994 subjects. We examined whether this association replicated in an African American sample from the Women's Health Initiative Single Nucleotide Polymorphism (SNP) Health Association Resource (WHI SHARe). Using this sample of 7800 postmenopausal women, of whom 316 have incident invasive breast cancer, we measured the genetic association of variants in ESR1 and breast cancer risk using Cox proportional hazards models adjusted for age, region, and principal components 1–4 taken from cluster analyses of genomic ancestry. All samples were genotyped on the Affymetrix 6.0 platform, and imputed with HapMap 2 populations (CEU and YRI) as reference. With regard to ER status, 68% of women in our sample (with known ER status) have ER-positive tumors. The most significant BCAC SNP, rs3020314, was not statistically significant in our study (HR: 1.09, 95% CI: 0.91–1.30) and we found no association between any of the other 130 SNPs tested in the ESR1 locus after Bonferroni correction. While our results for rs3020314 are in the same direction than the reported BCAC association it should be noted that the minor alleles differ by race; the C allele is more common in African Americans and the T allele is more common in BCAC (and the HapMap CEU sample). In our study, the minor (T) allele frequencies for rs3020314 are 0.295 for cases and 0.313 for controls. This lack of replication of the findings in intron 4 and the entire ESR1 locus suggests that ESR1 variants may not be associated with breast cancer in African American women. This may be due to a number of factors including linkage disequilibrium structure differences across races, small sample size and reduced power of the WHI sample, or may reflect disparity in tumor type, as African American women have a higher frequency of tumors that are estrogen receptor-negative.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B63.
Abstract B82: Health disparities of esophageal cancer by histological type in Puerto Rico: 2000–2004
Authors: González Lorena , Magno Priscilla , Ortiz Ana P. , Ortiz-Ortiz Karen , Nogueras Graciela , Suárez Erick
Published: June 2012

Background: Esophageal cancer (EC) has been ranked as the 8th most incident cancer and the 6th most common cause of death from cancer in the world. Hence, the primary aim of this study was to assess the age-standardized incidence (ASI) rates by histology type of EC in Puerto Rico (PR) and contrast these statistics with those of US Hispanics (USH), non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB) in the US.

Methods: We applied the direct method to compute the ASI rates for EC (per 100,000 persons) by histology type during 2000 to 2004, using the World Standard Population. The age specific relative risks (RR) and the overall comparison of two standardized rates (SRR) were estimated with 95% confidence intervals to determine relative differences among the study groups, during the same period of time, using the Poisson regression model and PR as reference.

Results: Overall, in PR during the years 2000–2004, the ASI rates (x 100,000 persons) for all EC were 16.8; among male 36.1 and among females 11.6. The risk of developing any histology type of EC in PR was higher than NHW for both sexes (SRRmales: 1.14, 95%CI: 1.02–1.28; SRRfemales: 1.27, 95%CI: 1.06–1.51) and USH (SRRmales: 1.45, 95%CI: 1.21–1.76; SRRfemales: 2.39, 95%CI: 1.74–3.35). PR also showed 2 to 3 times the risks of developing esophageal squamous cell carcinomas (ESCC) compared to NHW and USH for both sexes (p<0.05); only a risk reduction was observed when Puerto Rican males were compared to NHB males (p<0.05). Inversely, PR showed lower risks of developing esophageal adenocarcinomas (EAC) in comparison to NHW for both sexes (SRRmales: 0.29, 95%CI: 0.22–0.37; SRRfemales: 0.36, 95%CI: 0.21–0.55) and USH (SRRmales: 0.50, 95%CI: 0.35–0.70; SRRfemales: 0.71, 95%CI: 0.36–1.40).

Conclusions: Differences in EC incidence rates exist overall and by histology type among Puerto Ricans, NHW, NHB, and USH. Future research is warranted to elucidate the effect of the different risk factors and genetic predisposition for each histology type of EC in PR and among US racial/ethnic populations.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B82.
Abstract B94: The effect of clinic on identifying predictors of HPV co-testing with Pap in routine cervical cancer screening
Authors: Phelan Darcy F. , Boitnott John K. , Clark Douglas P. , Dubay Lisa C. , Gravitt Patti E.
Published: June 2012

Background: Human papillomavirus (HPV) co-testing with Pap is recommended for cervical cancer screening among women ≥ 30 years. However, little has been reported regarding actual provider use of HPV co-testing with Pap in clinical practice.

Purpose: We sought to identify predictors of HPV co-testing with Pap among women ≥ 30 years by utilizing laboratory and administrative data from the Johns Hopkins Hospital Division of Cytopathology in Baltimore, MD.

Methods: We analyzed 51,027 Pap specimen records and 4,148 HPV test records among 30,272 women ≥ 30 years in 88 clinics from February 2004 to December 2007. The outcome was HPV co-testing with Pap among women ≥ 30 years, and covariates included patient race, age, insurance type, ZIP code median household income, and calendar year. We constructed population-average logistic regression models. These included robust standard error estimation for clinic clustering and, at times, a fixed-effects estimator for within-clinic effects. We also stratified our analyses to five individual clinics.

Results: The overall proportion of HPV co-testing with Pap was 8.1%. Notably, 12.8% of Pap specimens of black women received HPV co-testing compared to 5.2% for specimens of white women and 6.2% for those of women of other races (p<0.01). Bivariate predictors of HPV co-testing with Pap among women ≥ 30 years included race, age, insurance type, ZIP code median household income, and calendar year. Most of these associations, however, could be explained by clinic-level differences in HPV co-testing. For example, the bivariate odds ratio for black race, OR 2.69 (95% CI 1.21–5.98), was modified to OR 0.92 (95% CI 0.82–1.03) by a fixed-effects estimator for clinic. Using five representative large clinics, clinic-stratified analyses did not support an independent association with HPV co-testing for race, insurance type, or ZIP code median household income, although an increase in HPV co-testing over time was observed in most clinics.

Conclusions: Under a population-average public health approach, the predictors of HPV co-testing with Pap varied between the pooled analyses and clinic stratified analyses. Using fixed-effects estimation to account for between-clinics effects in the pooled analyses provided further evidence for the substantial influence of clinics on the findings. This research suggests that the predictors of HPV co-testing with Pap among women ≥ 30 years likely lay at the provider and/or clinic level(s).

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B94.
Abstract ED04-03: Genetic variation among populations
Authors: Kidd Kenneth K.
Published: June 2012

Modern humans evolved in Africa and spread around the rest of the world only within the past 80 to 100 thousand years. During that process and subsequently allele frequency differences among the populations arose and those differences have great biomedical implications. The overall genetic pattern reflects the original expansion pathways out of Africa, but individual loci can vary greatly from that pattern. In contrast to the belief in distinct biological races, we see nearly continuous genetic variation across the globe among indigenous populations. While variation occurs, it is impossible to draw a line separating “races”. Examples of population variation in alleles relevant to cancer risk and therapeutic outcomes illustrate the global differences that do exist. Populations arising more recently with ancestry from geographically separated parts of the world have a mosaic pattern of ancestral DNA along their chromosomes such that an overall level of admixture is a poor predictor of the ancestral origins of alleles at any specified locus. These considerations become important in more personalized medicine.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):ED04-03.
Abstract PL04-04: Population impact: Using modeling to evaluate contributions of screening, treatment, and biology on disparities in breast cancer outcomes
Authors: Mandelblatt Jeanne
Published: June 2012

Purpose: U.S. Black women have higher breast cancer mortality rates than White women despite lower incidence. The disparity is growing and the reasons for this disparity remain uncertain. The aim of this study is to investigate how much of the mortality disparity can be attributed to racial differences in natural history, uptake of mammography screening and use of adjuvant therapy.

Methods: Two simulation models use common national race- and age-specific data for incidence, screening and treatment dissemination, stage distributions, survival and competing mortality from 1975 to 2010. Treatment effectiveness and mammography sensitivity are assumed to be the same for both races. We sequentially substituted Black parameters into the White model to identify parameters that drive the higher mortality for Black women in the current time period (2004–2006).

Results: Both models accurately reproduced observed breast cancer incidence, stage and tumor size distributions and breast cancer mortality for White women. The higher mortality for Black women could be attributed to differences in natural history parameters (26–44%), use of adjuvant therapy (11–19%) and uptake of mammography screening (7–8%), leaving 38–46% unexplained.

Conclusion: Black women appear to have benefited less from cancer control advances than White women, with a greater race-related gap in the use of adjuvant therapy than mammography screening. However, a greater portion of the disparity in breast cancer mortality appears to be due to differences in natural history and undetermined factors.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL04-04.
Abstract PL06-02: Patient navigation and timeliness of diagnostic evaluation: Results from the Patient Navigation Research Program
Authors: Freund Karen M. , Paskett Electra , Corle Donald , Snyder Frederick R. , Calhoun Elizabeth , Dudley Donald J. , Murray David M. , Patierno Steven , Roetzheim Richard G. , Warren-Mears Victoria , Whitley Elizabeth , Winters Paul C.
Published: June 2012

Background: Patient navigation has been proposed as a means to reduce cancer health disparities, through the addition of a trained navigator to the health care team. Patient navigators help patients to identify barriers to receiving needed care, and to develop individually targeted plans to overcome these barriers. The Patient Navigation Research Program is a nine-site program to evaluate the benefit of patient navigation among underserved populations from diverse socioeconomic and geographic locations within the United States.

Methods: Patients with breast, cervical, colorectal or prostate screening abnormalities were eligible for enrollment. The primary outcome was time to diagnostic resolution of the screening abnormality, assessed dichotomously as resolved or not within 365 days, and analyzed using survival curves and Cox proportional hazards models of time to resolution by 12 months. Due to the differing study designs at the 9 sites (RCT, Group randomized, and non randomized group allocation) we calculated an effect size for each cancer type for each site, and utilized a meta-analysis to assess an overall effect size. Models were adjusted for age, race, insurance and marital status.

Results: There were 10,513 subjects (5,055 Navigated and 5,458 Non-navigated) recruited from the 9 sites, 64% with breast cancer screening abnormalities. The study population was diverse with 74% from minority groups (32% African American, 39% Latino, 4% other), and low income with 17% Medicaid insured, and 32% with no insurance. In the control population, 62% to 95% of the participants did not reach diagnostic resolution after their abnormal screening result within 12 months. Those in the navigation arm were more likely to reach resolution after an abnormal test in 13 of the 15 cancer sites, (89 to 99% resolved). Of the 15 hazard rate ratios, 11 showed a statistically significant positive effect of the navigation intervention, 3 others showed a non statistically significant benefit of navigation, and 1 showed a negative effect of navigation on time to diagnostic resolution, (effect sizes ranging from an adjusted HR of 0.38 to 3.94, with a higher HR favoring the navigation arm).

Implications: Compared to non-navigated subjects, participants with an abnormal cancer screening test who were allocated to receive a patient navigation intervention were more likely to receive timely diagnostic resolution of their abnormal screening test. Patient navigation for vulnerable populations may be beneficial in reducing cancer disparities.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL06-02.
Abstract PL06-05: The cost effectiveness of patient navigation
Authors: Bensink Mark E. , Ramsey Scott D. , Raich Peter C. , Seiber Eric , Warren-Mears Victoria , Mandelblatt Jeanne S. , Battaglia Tracy , Everhart Rachel M. , Fiscella Kevin , Freund Karen , Hurd Thelma C. , McKoy June M. , Paskett Electra D. , Patierno Steven R.
Published: June 2012

Navigation requires investment, investment in training and establishing navigators and supporting them to provide navigation to patients. The cost-effectiveness of patient navigation weighs the investment required against the effect produced. The result is a measure of the value provided by navigation. The aim of this presentation is to present data from the PNRP experience estimating the investment required to implement patient navigation and the resulting economic impact on diagnostic and treatment services, weighed against the effect of patient navigation on the PNRP intermediate outcomes of time to diagnosis, time to treatment, patient satisfaction and patient quality of life.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL06-05.
Abstract PR2: Warburg effect revisited: Glucose addiction in precancerous mammary epithelial cells in African American women
Authors: Ibarra-Drendall Catherine , Sistrunk Chris , Hoffman Abigail , Ford Ane , Seewaldt Victoria Louise
Published: June 2012

Background: Only 14% of African American women with triple-negative breast cancers will be alive at one year. Early detection is greatly needed. Here we aimed to investigate whether activation of biologic pathways that predict aggressive triple-negative breast cancers are also activated in atypia in high-risk African American women. Aggressive cancers are known to consume glucose avidly and produce lactic acid (rather than fully metabolize glucose via the Tricarboxylic Acid (TCA) cycle). This shift toward lactate production, even in the presence of adequate oxygen, is termed the Warburg effect. The Warburg effect is thought to be a late event in breast cancer, however, our studies in high-risk African American women provide evidence that the Warburg effect occurs during cancer initiation. This is an important observation as glucose-signaling can be readily targeted for breast cancer prevention with minimal toxicity. Here we investigated the role of the Warburg effect in breast cancer initiation in young high-risk African American women.

Methods and Results: Similar to fluorodeoxyglucose, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) is a fluorescent glucose analog that can be used to track glucose uptake and glycolysis. 2-NBDG spectroscopy provides a means to track glucose metabolism in live mammary epithelial cells from high-risk women. We used 2-NBDG spectroscopy to measure glucose uptake in ER-breast cancer and live atypical mammary epithelial cells from high-risk premenopausal women. We observe that both triple-negative breast cancer and a subset of atypia exhibits accumulation of 2-NBDG.

There is growing recognition that phosphoprotein signaling networks (rather than single genes) play a key role in breast cancer initiation and progression. Our team used Reverse Phase Proteomic Microarray (RPPM) profiling to test for activation of phosphoprotein signaling networks in atypical RPFNA cytology from high-risk premenopausal women in our cohort. RPFNA were obtained from two independent sets of 39 and 38 high-risk premenopausal women; 45% of these women were African American. The signaling network most highly expressed in precancerous cells contained activated signaling proteins associated with the Warburg effect (AKT/mTOR/PI3K), insulin signaling (pACC, IRS1) and epithelial to mesenchymal transition (EMT) IL6/Stat3/vimentin.

Conclusions: This is the first evidence that abnormal glucose uptake and the Warburg effect occurs during breast cancer initiation in high-risk African American premenopausal women. These studies demonstrate our ability to identify abnormal glucose and activated signaling networks associated with the Warburg effect in atypical mammary cells from high-risk African American women and provide an important target for breast cancer early detection and prevention.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PR2.