|
1
|
Lee SM, Oh H. RAS/RAF mutations and microsatellite instability status in primary colorectal cancers according to HER2 amplification. Sci Rep 2024; 14:11432. [PMID: 38763942 PMCID: PMC11102903 DOI: 10.1038/s41598-024-62096-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 05/13/2024] [Indexed: 05/21/2024] Open
Abstract
HER2 amplification-associated molecular alterations and clinicopathologic features in colorectal cancers (CRCs) have not been well established. In this study, we assessed the prevalence of HER2 amplification and microsatellite instability (MSI) status of 992 patients with primary CRC. In addition, molecular alterations of HER2 amplified and unamplified CRCs were examined and compared by next-generation sequencing. HER2 amplifications were found in 41 (4.1%) of 992 primary CRCs. HER2 amplification was identified in 1.0% of the right colonic tumors, 5.1% of the left colonic tumors, and 4.8% of the rectal tumors. Approximately 95% of HER2 amplification was observed in the left colon and rectum. Seven (87.5%) of eight metastatic tumors showed HER2 amplification. Most clinicopathologic features were unrelated to HER2 amplification except tumor size and MSI status. All 41 HER2 amplified CRCs were microsatellite stable. In a molecular analysis of frequently identified somatic mutations in CRCs, HER2 amplified CRCs showed a lower rate of KRAS mutations (24.4%) but a higher rate of TP53 mutations (83%) than unamplified CRCs. No BRAF and NRAS mutations were identified in HER2 amplified CRCs. Our study suggests that HER2 amplified CRCs are mutually exclusive of MSI and harbor less frequent KRAS/NRAS/BRAF mutations but frequent T53 mutations.
Collapse
Affiliation(s)
- Sun Mi Lee
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W. 11th Street, Indianapolis, IN, 46202, USA.
- Department of Pathology, Jeju National University Hospital, Jeju-si, South Korea.
| | - Hyunjoo Oh
- Department of Internal Medicine, Jeju National University Hospital, Jeju-si, South Korea
| |
Collapse
|
|
2
|
Moten AS, Taylor GA, Fagenson AM, Poggio JL, Philp MM, Lau KN. Diminishing racial disparities in the treatment of colon adenocarcinoma. SURGERY IN PRACTICE AND SCIENCE 2023; 13:100166. [PMID: 39845396 PMCID: PMC11749994 DOI: 10.1016/j.sipas.2023.100166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 04/11/2023] [Indexed: 01/24/2025] Open
Abstract
Background Prior research has demonstrated racial disparities in the treatment of colon cancer. We sought to determine if treatment disparities persist. Methods Patients with colon adenocarcinoma diagnosed from 2012 to 2016 were identified using the Surveillance, Epidemiology and End Results database. Associations between race and clinical characteristics were assessed using Chi square tests. The likelihood of receiving treatment based on race was assessed using logistic regression. Results Of 18,841 patients, 69.7% were White, 10.2% Black, 8.7% Hispanic and 11.4% Asian. Among patients with early-stage disease (stage I or II), 96.1% of Whites, 94.6% of Blacks, 95.6% of Hispanics and 97.7% of Asians underwent surgery (p = 0.01), while 8.9% of Whites, 9.3% of Blacks, 12.4% of Hispanics and 8.9% of Asians received chemotherapy (p = 0.03). For years 2012 to 2016 collectively, Blacks with early-stage disease were less likely than Whites to undergo any surgery (aOR = 0.54; 95% CI: 0.36 - 0.81) and more likely to receive neither surgery nor chemotherapy (aOR = 1.91; 95% CI: 1.25 - 2.93). However, when assessing each year individually, the most recent years revealed no difference in the likelihood of receiving surgery in (aOR = 0.45; 95% CI: 0.16 - 1.29 in 2016) or receiving neither surgery nor chemotherapy (aOR = 2.17; 95% CI: 0.70 - 6.70 in 2016). Conclusion Racial disparities in the treatment of colon adenocarcinoma have improved in recent years. Health care providers must continue to provide equitable, evidence-based care to ensure that treatment disparities are eliminated.
Collapse
Affiliation(s)
- Ambria S Moten
- Division of Surgical Oncology, Department of Surgery, University of Tennessee Health Science Center, 875 Monroe Ave, Memphis, TN 38163, USA
| | - George A Taylor
- Department of Surgery, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, USA
| | - Alexander M Fagenson
- Department of Surgery, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, USA
| | - Juan Lucas Poggio
- Department of Surgery, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, USA
- Lewis Katz School of Medicine at Temple University, 3500 N Broad Street, Philadelphia, PA 19140, USA
| | - Matthew M Philp
- Department of Surgery, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, USA
- Lewis Katz School of Medicine at Temple University, 3500 N Broad Street, Philadelphia, PA 19140, USA
| | - Kwan N. Lau
- Department of Surgery, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, USA
- Lewis Katz School of Medicine at Temple University, 3500 N Broad Street, Philadelphia, PA 19140, USA
| |
Collapse
|
|
3
|
Baker FA, Taher R, Ganayem M, Mari A, Kopelman Y. Ethnic disparities in colorectal cancer outcomes : a population study from Israel. ETHNICITY & HEALTH 2022; 27:554-564. [PMID: 32692255 DOI: 10.1080/13557858.2020.1795630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 07/09/2020] [Indexed: 06/11/2023]
Abstract
Objectives: Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Clear ethnic disparities in the incidence of CRC and its outcomes have been observed globally, but only few research efforts have been invested so far in the unique ethnic scene of Israeli population. This study aims to compare the clinico-pathologic features, tumor's characteristics and prognosis between Arab and Jewish CRC patients as well as among Jewish subgroups living within the same central coastal region in Israel.Methods: In this retrospective, single center study, a total of 401 patients with pathologically confirmed CRCs diagnosed during the years 2008-2015 were included. These were divided into Jewish (n = 334) and Arab (n = 67) groups. Data collected included demographics, country of birth, clinical presentation and family history. Tumor stage, location, histologic grade and mortality rate were compared retrospectively between both groups and within Jewish sub-populations.Results: Arabs were significantly younger at diagnosis (62.7 ± 12.9 vs. 69.3 ± 13.01; P < 0.01), presented more frequently with rectal bleeding, and were less likely to be diagnosed due to positive fecal occult blood test (9% vs. 22.6%; P = 0.012). Tumor distribution through the colon was comparable between both groups and characterized by a distal predominance. Arabs had a significantly higher rate of advanced stage at diagnosis (58% vs. 50.5%, OR = 2.454, 95%CI = 1.201-5.013; P = 0.02) when compared to Jews. Mortality rates were comparable between both groups. In the Jewish subpopulation analysis, we found that immigrants, especially those born in the former USSR, presented with significantly advanced tumor stages when compared to native Israelis (55% vs. 37.5%; P = 0.02).Conclusion: CRC in two major ethnic populations in Israel, Arabs and Jews, varied in terms of age at diagnosis, clinical presentation and stage at diagnosis. Similar findings were documented within a non-native Jewish subpopulation, raising the possibility of a low utilization of screening programs in these groups.
Collapse
Affiliation(s)
- Fadi Abu Baker
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center (Affiliated to the Technion Faculty of Medicine, Haifa, Israel), Hadera, Israel
| | - Randa Taher
- Department of Internal Medicine, Hillel Yaffe Medical Center (Affiliated to the Technion Faculty of Medicine, Haifa, Israel), Hadera, Israel
| | - Mohanad Ganayem
- Department of Internal Medicine, Hillel Yaffe Medical Center (Affiliated to the Technion Faculty of Medicine, Haifa, Israel), Hadera, Israel
| | - Amir Mari
- Department of Gastroenterology, Nazareth EMMS Hospital (Affiliated with the Faculty of Medicine, Bar Illan University), Nazareth, Israel
| | - Yael Kopelman
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center (Affiliated to the Technion Faculty of Medicine, Haifa, Israel), Hadera, Israel
| |
Collapse
|
|
4
|
Lee S, Zhang S, Ma C, Ou FS, Wolfe EG, Ogino S, Niedzwiecki D, Saltz LB, Mayer RJ, Mowat RB, Whittom R, Hantel A, Benson A, Atienza D, Messino M, Kindler H, Venook A, Gross CP, Irwin ML, Meyerhardt JA, Fuchs CS. Race, Income, and Survival in Stage III Colon Cancer: CALGB 89803 (Alliance). JNCI Cancer Spectr 2021; 5:pkab034. [PMID: 34104867 PMCID: PMC8178799 DOI: 10.1093/jncics/pkab034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 12/10/2020] [Accepted: 02/19/2021] [Indexed: 01/01/2023] Open
Abstract
Background Disparities in colon cancer outcomes have been reported across race and socioeconomic status, which may reflect, in part, access to care. We sought to assess the influences of race and median household income (MHI) on outcomes among colon cancer patients with similar access to care. Methods We conducted a prospective, observational study of 1206 stage III colon cancer patients enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial. Race was self-reported by 1116 White and 90 Black patients at study enrollment; MHI was determined by matching 973 patients’ home zip codes with publicly available US Census 2000 data. Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary, and lifestyle factors. All statistical tests were 2-sided. Results Over a median follow-up of 7.7 years, the adjusted hazard ratios for Blacks (compared with Whites) were 0.94 (95% confidence interval [CI] = 0.66 to 1.35, P = .75) for disease-free survival, 0.91 (95% CI = 0.62 to 1.35, P = .65) for recurrence-free survival, and 1.07 (95% CI = 0.73 to 1.57, P = .73) for overall survival. Relative to patients in the highest MHI quartile, the adjusted hazard ratios for patients in the lowest quartile were 0.90 (95% CI = 0.67 to 1.19, Ptrend = .18) for disease-free survival, 0.89 (95% CI = 0.66 to 1.22, Ptrend = .14) for recurrence-free survival, and 0.87 (95% CI = 0.63 to 1.19, Ptrend = .23) for overall survival. Conclusions In this study of patients with similar health-care access, no statistically significant differences in outcomes were found by race or MHI. The substantial gaps in outcomes previously observed by race and MHI may not be rooted in differences in tumor biology but rather in access to quality care.
Collapse
Affiliation(s)
| | - Sui Zhang
- Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA
| | - Chao Ma
- Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA
| | - Fang-Shu Ou
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA
| | - Eric G Wolfe
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA
| | - Shuji Ogino
- Department of Oncologic Pathology, Dana-Farber/Partners CancerCare and Harvard Medical School, Boston, MA, USA.,Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Donna Niedzwiecki
- Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA
| | | | - Robert J Mayer
- Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA
| | - Rex B Mowat
- Toledo Community Hospital Oncology Program, Toledo, OH, USA
| | | | - Alexander Hantel
- Loyola University Stritch School of Medicine, Naperville, IL, USA
| | - Al Benson
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | | | - Michael Messino
- Southeast Clinical Oncology Research Consortium, Mission Hospitals, Asheville, NC, USA
| | - Hedy Kindler
- University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
| | - Alan Venook
- University of California at San Francisco Comprehensive Cancer Center, San Francisco, CA, USA
| | - Cary P Gross
- Yale School of Medicine, Department of Internal Medicine, New Haven, CT, USA
| | | | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA
| | - Charles S Fuchs
- Yale School of Medicine, New Haven, CT, USA.,Yale Cancer Center, Smilow Cancer Hospital and Yale School of Medicine, New Haven, CT, USA.,Genentech, South San Francisco, CA, USA
| |
Collapse
|
|
5
|
Wu W, Yang J, Li D, Huang Q, Zhao F, Feng X, Yan H, Lyu J. Competitive Risk Analysis of Prognosis in Patients With Cecum Cancer: A Population-Based Study. Cancer Control 2021; 28:1073274821989316. [PMID: 33491489 PMCID: PMC8482702 DOI: 10.1177/1073274821989316] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: The presence of competing risks means that the results obtained using the classic Cox proportional-hazards model for the factors affecting the prognosis of patients diagnosed with cecum cancer (CC) may be biased. Objective: The purpose of this study was to establish a competitive risk model for patients diagnosed with CC to evaluate the relevant factors affecting the prognosis of patients, and to compare the results with the classical COX proportional risk model. Methods: We extracted data on patients diagnosed with CC registered between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate analysis utilized the cumulative incidence function and Gray’s test, while a multivariate analysis was performed using the Fine-Gray, cause-specific (CS), and Cox proportional-hazards models. Results: The 54463 eligible patients diagnosed with CC included 24387 who died: 12087 from CC and 12300 from other causes. The multivariate Fine-Gray analysis indicated that significant factors affecting the prognosis of patients diagnosed with CC include: age, race, AJCC stage, differentiation grade, tumor size, surgery, radiotherapy, chemotherapy and regional lymph nodes metastasis. Due to the presence of competitive risk events, COX model results could not provide accurate estimates of effects and false-negative results occurred. In addition, COX model misestimated the direction of association between regional lymph node metastasis and cumulative risk of death in patients diagnosed with CC. Competitive risk models tend to be more advantageous when analyzing clinical survival data with multiple endpoints. Conclusions: The present study can help clinicians to make better clinical decisions and provide patients diagnosed with CC with better support.
Collapse
Affiliation(s)
- Wentao Wu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Jin Yang
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Daning Li
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Qiao Huang
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Fanfan Zhao
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Xiaojie Feng
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Hong Yan
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Jun Lyu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| |
Collapse
|
|
6
|
Augustus GJ, Ellis NA. Colorectal Cancer Disparity in African Americans: Risk Factors and Carcinogenic Mechanisms. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 188:291-303. [PMID: 29128568 DOI: 10.1016/j.ajpath.2017.07.023] [Citation(s) in RCA: 118] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 07/01/2017] [Accepted: 07/20/2017] [Indexed: 12/13/2022]
Abstract
African Americans have the highest incidence and mortality rates of colorectal cancer (CRC) of any ethnic group in the United States. Although some of these disparities can be explained by differences in access to care, cancer screening, and other socioeconomic factors, disparities remain after adjustment for these factors. Consequently, an examination of recent advances in the understanding of ethnicity-specific factors, including genetic and environmental factors relating to risk of CRC, the biology of CRC progression, and the changes in screening and mortality, is important for evaluating our progress toward eliminating the disparities. An overarching limitation in this field is the number and sample size of studies performed to characterize the etiological bases of CRC incidence and mortality in African Americans. Despite this limitation, significant differences in etiology are manifest in many studies. These differences need validation, and their impacts on disparities need more detailed investigation. Perhaps most heartening, improvements in CRC screening can be attributed to the smallest difference in CRC incidence between African Americans and whites since the late 1980s. Cancer mortality, however, remains a persistent difference.
Collapse
Affiliation(s)
- Gaius J Augustus
- Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, Arizona.
| | - Nathan A Ellis
- University of Arizona Cancer Center, University of Arizona, Tucson, Arizona; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona.
| |
Collapse
|
|
7
|
Ashktorab H, Ahuja S, Kannan L, Llor X, Ellis NA, Xicola RM, Laiyemo AO, Carethers JM, Brim H, Nouraie M. A meta-analysis of MSI frequency and race in colorectal cancer. Oncotarget 2017; 7:34546-57. [PMID: 27120810 PMCID: PMC5085175 DOI: 10.18632/oncotarget.8945] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 03/28/2016] [Indexed: 01/19/2023] Open
Abstract
PURPOSE African Americans (AA) are at a higher risk of colorectal cancer (CRC) and some studies report a higher frequency of microsatellite instability (MSI) in this population while others report lower frequency compared to Caucasians. AIM To determine and evaluate the association of race and clinical factors with MSI frequency through meta- analysis. METHODS Twenty-two studies out of 15,105 (1997-2015) were evaluated after a search in different literature databases, using keywords “colorectal cancer, microsatellite instability, African Americans, Caucasians and Hispanics”. We used random effect meta-analysis to calculate the MSI frequency in all studies as well as in African American and Caucasian samples. Meta-regression analysis was used to assess the univariate effect of race, gender, age, tumor location and stage on MSI frequency. RESULTS The overall MSI frequency among CRCs was 17% (95%CI: 15%-19%, I²=91%). In studies with available race data, The MSI rate among AAs, Hispanics and Caucasians were 12%, 12% and 14% respectively and was not significantly different. Sub-group analysis of studies with racial information indicates MSI OR of 0.78 for AAs compared to Caucasians. CONCLUSION CRCs demonstrate an overall MSI frequency of 17%. MSI frequency differences between AAs and Caucasians were not pronounced, suggesting that other factors contribute to the racial disparity. The methodological approaches and biological sources of the variation seen in MSI frequency between different studies need to be further investigated.
Collapse
Affiliation(s)
- Hassan Ashktorab
- Department of Medicine and Cancer Center, Howard University College of Medicine, Washington DC, USA
| | - Sadhna Ahuja
- Department of Pathology, Howard University College of Medicine, Washington DC, USA
| | - Lakshmi Kannan
- Department of Medicine and Cancer Center, Howard University College of Medicine, Washington DC, USA
| | - Xavier Llor
- Department of Medicine and Cancer Center, Yale University, New Haven, CT, USA
| | - Nathan A Ellis
- Cancer Biology Research Program, The University of Arizona Cancer Center, Tucson, AZ, USA
| | - Rosa M Xicola
- Department of Medicine and Cancer Center, Yale University, New Haven, CT, USA
| | - Adeyinka O Laiyemo
- Department of Medicine and Cancer Center, Howard University College of Medicine, Washington DC, USA
| | - John M Carethers
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Hassan Brim
- Department of Pathology, Howard University College of Medicine, Washington DC, USA
| | - Mehdi Nouraie
- Department of Medicine and Cancer Center, Howard University College of Medicine, Washington DC, USA
| |
Collapse
|
|
8
|
Manne U, Jadhav T, Putcha BDK, Samuel T, Soni S, Shanmugam C, Suswam EA. Molecular Biomarkers of Colorectal Cancer and Cancer Disparities: Current Status and Perspective. CURRENT COLORECTAL CANCER REPORTS 2016. [PMID: 28626361 DOI: 10.1007/s11888-016-0338-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
This review provides updates on the efforts for the development of prognostic and predictive markers in colorectal cancer based on the race/ethnicity of patients. Since the clinical consequences of genetic and molecular alterations differ with patient race and ethnicity, the usefulness of these molecular alterations as biomarkers needs to be evaluated in different racial/ethnic groups. To accomplish personalized patient care, a combined analysis of multiple molecular alterations in DNA, RNA, microRNAs (miRNAs), metabolites, and proteins in a single test is required to assess disease status in a precise way. Therefore, a special emphasis is placed on issues related to utility of recently identified genetic and molecular alterations in genes, miRNAs, and various "-omes" (e.g., proteomes, kinomes, metabolomes, exomes, methylomes) as candidate molecular markers to determine cancer progression (disease recurrence/relapse and metastasis) and to assess the efficacy of therapy in colorectal cancer in relation to patient race and ethnicity. This review will be useful for oncologists, pathologists, and basic and translational researchers.
Collapse
Affiliation(s)
- Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.,Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.,Comprehensive Cancer Center, Wallace Tumor Institute, University of Alabama at Birmingham, Room # 420A, 1530 3rd Avenue South, Birmingham, AL 35294, USA
| | - Trafina Jadhav
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.,Wallace Tumor Institute, University of Alabama at Birmingham, Room # 430A, 1530 3rd Avenue South, Birmingham, AL 35294, USA.,Present address: Division of Cardiovascular Medicine, Vanderbilt University, 1215 21st Avenue South, Medical Center East, Suite 5050, Nashville, TN 37232-8802, USA
| | - Balananda-Dhurjati Kumar Putcha
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.,Wallace Tumor Institute, University of Alabama at Birmingham, Room # 430A, 1530 3rd Avenue South, Birmingham, AL 35294, USA.,Present address: 2502 East Woodlands, Saint Joseph, MO 64506, USA
| | - Temesgen Samuel
- Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA
| | - Shivani Soni
- Department of Biological Sciences, Alabama State University, Room # 325, Life Science Building, 1627, Hall Street, Montgomery, AL 36104, USA
| | - Chandrakumar Shanmugam
- Wallace Tumor Institute, University of Alabama at Birmingham, Room # 430A, 1530 3rd Avenue South, Birmingham, AL 35294, USA.,Present address: Department of Pathology, ESIC Medical College and Hospital, Sanathnagar, Hyderabad, Telangana 500 038, India
| | - Esther A Suswam
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.,Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.,Department of Pathology, Wallace Tumor Institute, University of Alabama at Birmingham, 1720 2nd Avenue South, # 410C, Birmingham, AL 35294-3300, USA
| |
Collapse
|
|
9
|
A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer. BMC Cancer 2016; 16:368. [PMID: 27316467 PMCID: PMC4912774 DOI: 10.1186/s12885-016-2365-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 05/16/2016] [Indexed: 01/08/2023] Open
Abstract
Background African American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer. Methods We retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions. The 12-gene assay and mismatch repair (MMR) status were performed by Genomic Health (Redwood City, California). Student’s t-test and the Wilcoxon rank sum test were used to compare Recurrence Score data and gene expression data from AA and CA patients (SAS Enterprise Guide 5.1). Results Samples from 122 AA and 122 CA patients were analyzed. There were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median age was 66 years for AA patients and 68 for CA patients. Age, gender, year of surgery, pathologic T-stage, tumor location, the number of lymph nodes examined, lymphovascular invasion, and MMR status were not significantly different between groups (p = 0.93). The mean Recurrence Score result for AA patients (27.9 ± 12.8) and CA patients (28.1 ± 11.8) was not significantly different and the proportions of patients with high Recurrence Score values (≥41) were similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC and GADD45B), was significantly different between the racial groups. After controlling for clinical and pathologic covariates, the means and distributions of Recurrence Score results and gene expression profiles showed no statistically significant difference between patient groups. Conclusion The distribution of Recurrence Score results and gene expression data was similar in a cohort of AA and CA patients with stage II colon cancer and similar clinical characteristics, suggesting that tumor biology, as represented by the 12-gene assay, did not differ between patient groups.
Collapse
|
|
10
|
Lai Y, Wang C, Civan JM, Palazzo JP, Ye Z, Hyslop T, Lin J, Myers RE, Li B, Jiang BH, Sama A, Xing J, Yang H. Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study. Gastroenterology 2016; 150:1135-1146. [PMID: 26836586 PMCID: PMC4842115 DOI: 10.1053/j.gastro.2016.01.030] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Revised: 01/20/2016] [Accepted: 01/24/2016] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage. METHODS We collected data from the Surveillance, Epidemiology, and End Results-Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed up through 2011. Three sets of 6190 white patients were matched sequentially, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age; sex; diagnosis year; and Surveillance, Epidemiology, and End Results registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a subcohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS After patients were matched for demographic variables, the absolute 5-year difference in survival between black and white patients was 8.3% (white, 59.2% 5-y survival; blacks, 50.9% 5-y survival) (P < .0001); this value decreased significantly, to 5.0% (P < .0001), after patients were matched for tumor presentation, and decreased to 4.9% (P < .0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to an 11.1% difference) vs early stage cancer (stages I or II, up to a 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5-year racial survival disparity was 7.7% after demographic match, which was less than the 8.3% observed in the complete cohort. This reduction likely was owing to the differences between the subcohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% (P = .0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% (P = .090) after tumor presentation match, but was not reduced further after treatment match. CONCLUSIONS We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been affected more strongly by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage vs early-stage cancer.
Collapse
Affiliation(s)
- Yinzhi Lai
- Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Chun Wang
- Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Jesse M. Civan
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Juan P. Palazzo
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Zhong Ye
- Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Terry Hyslop
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA
| | - Jianqing Lin
- Division of Solid Tumor Oncology, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Ronald E. Myers
- Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Bingshan Li
- Center for Human Genetics Research, Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN 37232, USA
| | - Bing-Hua Jiang
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Ashwin Sama
- Division of Solid Tumor Oncology, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Jinliang Xing
- Experimental Teaching Center, School of Basic Medicine, Fourth Military Medical University, Xi’an, 710032, China
| | - Hushan Yang
- Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
| |
Collapse
|
|
11
|
Yoon HH, Shi Q, Alberts SR, Goldberg RM, Thibodeau SN, Sargent DJ, Sinicrope FA. Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients. J Natl Cancer Inst 2015; 107:djv186. [PMID: 26160882 PMCID: PMC5758035 DOI: 10.1093/jnci/djv186] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 04/28/2015] [Accepted: 06/19/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND It is unknown if, after controlling for clinicopathologic variables and treatment, racial disparities in colon cancer outcomes persist. Molecular marker analysis in North American patients comparing Asians with other races has not been reported. METHODS BRAF (V600E) and KRAS mutations were analyzed in node-positive colon cancer patients (n = 3305) treated with FOLFOX-based chemotherapy in an adjuvant trial (Alliance N0147). Race categories included Asian, black, or white. Cox models were used to estimate disease-free survival (DFS) and time to recurrence (TTR). All statistical tests were two-sided. RESULTS BRAF mutation frequency in tumors from whites (13.9%) was twice that of tumors from Asians or blacks. KRAS mutation rates were highest in tumors from blacks (44.1%). KRAS/BRAF wild-type tumors were most common among Asians (66.7%) (P overall < .001). The prognostic impact of race differed by age and N stage (both P interaction < .02). Compared with whites, blacks had shorter DFS among patients younger than age 50 years (hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 1.73 to 4.66) or with N1 disease (HR = 1.54, 95% CI = 1.04 to 2.29), independent of BRAF, KRAS, and other covariates. Findings were consistent using TTR as the outcome. Asians had longer DFS among N2 tumors that was partly mediated by less frequent BRAF mutation. CONCLUSIONS Colon cancers from Asians have a lower rate of BRAF and KRAS mutations than blacks or whites. We report a novel interaction of race with age and N stage in node-positive disease, indicating that racial disparities in survival persist despite uniform stage and treatment in a phase III trial.
Collapse
Affiliation(s)
- Harry H Yoon
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
| | - Qian Shi
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG)
| | - Steven R Alberts
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG)
| | - Richard M Goldberg
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG)
| | - Stephen N Thibodeau
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG)
| | - Daniel J Sargent
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG)
| | - Frank A Sinicrope
- Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
| |
Collapse
|
|
12
|
Fang SH, Efron JE, Berho ME, Wexner SD. Dilemma of stage II colon cancer and decision making for adjuvant chemotherapy. J Am Coll Surg 2014; 219:1056-69. [PMID: 25440029 DOI: 10.1016/j.jamcollsurg.2014.09.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Revised: 05/14/2014] [Accepted: 05/22/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Sandy H Fang
- Colon and Rectal Surgery, Department of Surgery, Ravitch Division, Johns Hopkins Medical Center, Baltimore, MD
| | - Jonathan E Efron
- Colon and Rectal Surgery, Department of Surgery, Ravitch Division, Johns Hopkins Medical Center, Baltimore, MD
| | - Mariana E Berho
- Department of Pathology, Cleveland Clinic Florida, Weston, FL.
| | - Steven D Wexner
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL
| |
Collapse
|
|
13
|
Kang M, Shen XJ, Kim S, Araujo-Perez F, Galanko JA, Martin CF, Sandler RS, Keku TO. Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer. Cancer Biomark 2014; 13:359-66. [PMID: 24440976 DOI: 10.3233/cbm-130366] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVE African Americans have worse outcomes in colorectal cancer (CRC) than Caucasians. We sought to determine if KRAS, BRAF and PIK3CA mutations might contribute to the racial differences in CRC outcome. METHODS DNA was extracted from tissue microarrays made from CRC samples from 67 African Americans and 237 Caucasians. Mutations in KRAS, BRAF, and PIK3CA were evaluated by PCR sequencing. We also examined microsatellite instability (MSI) status. Associations of mutation status with tumor stage and grade were examined using a logistic regression model. Cox proportional hazards models were used to estimate the all-cause mortality associated with mutational status, race and other clinicopathologic features. RESULTS KRAS mutations were more common in African Americans than among Caucasians (37% vs 21%, p=0.01) and were associated with advanced stage (unadjusted odds ratio (OR)=3.31, 95% confidence interval (CI) 1.03-10.61) and grade (unadjusted OR=5.60, 95% CI 1.01-31.95) among African Americans. Presence of BRAF mutations was also positively associated with advanced tumor stage (adjusted OR=3.99, 95%CI 1.43-11.12) and grade (adjusted OR=3.93, 95%CI 1.05-14.69). PIK3CA mutations showed a trend toward an association with an increased risk of death compared to absence of those mutations (adjusted for age, sex and CRC site HR=1.89, 95% CI 0.98-3.65). Among African Americans, the association was more evident (adjusted for age, sex and CRC site HR=3.92, 95% CI 1.03-14.93) and remained significant after adjustment for MSI-H status and combined education-income level, with HR of 12.22 (95%CI 1.32-121.38). CONCLUSIONS Our results suggest that African Americans may have different frequencies of somatic genetic alterations that may partially explain the worse prognosis among African Americans with CRC compared to whites.
Collapse
Affiliation(s)
- Melissa Kang
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Xiang J Shen
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Sangmi Kim
- Georgia Regents University Cancer Center, Section of Hematology/Oncology, Department of Medicine, Medical College of Georgia, Augusta, GA, USA
| | - Felix Araujo-Perez
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Joseph A Galanko
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Chris F Martin
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Robert S Sandler
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Temitope O Keku
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| |
Collapse
|
|
14
|
Tammana VS, Laiyemo AO. Colorectal cancer disparities: Issues, controversies and solutions. World J Gastroenterol 2014; 20:869-876. [PMID: 24574761 PMCID: PMC3921540 DOI: 10.3748/wjg.v20.i4.869] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Revised: 11/14/2013] [Accepted: 12/06/2013] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. There are significant differences in CRC incidence and mortality by race with the highest burden occurring among blacks. The underlying factors contributing to CRC disparities are multiple and complex. Studies have suggested that a higher prevalence of putative risk factors for CRC, limited access to healthcare services, lower utilization of healthcare resources and increased biological susceptibilities contribute to this disparity by race. This article reviews the factors associated with the disproportionally higher burden of CRC among blacks; addresses the controversies regarding the age to begin CRC screening and the screening modality to use for blacks; and proffers solutions to eliminate CRC disparity by race.
Collapse
|
|
15
|
Hanna MC, Go C, Roden C, Jones RT, Pochanard P, Javed AY, Javed A, Mondal C, Palescandolo E, Van Hummelen P, Hatton C, Bass AJ, Chun SM, Na DC, Kim TI, Jang SJ, Osarogiagbon RU, Hahn WC, Meyerson M, Garraway LA, MacConaill LE. Colorectal cancers from distinct ancestral populations show variations in BRAF mutation frequency. PLoS One 2013; 8:e74950. [PMID: 24066160 PMCID: PMC3774610 DOI: 10.1371/journal.pone.0074950] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 08/06/2013] [Indexed: 02/07/2023] Open
Abstract
It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer.
Collapse
Affiliation(s)
- Megan C. Hanna
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- The Broad Institute, Cambridge, Massachusetts, United States of America
| | - Christina Go
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Christine Roden
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Robert T. Jones
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Panisa Pochanard
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Ahmed Yasir Javed
- Boston Baskin Cancer Foundation, Baptist Cancer Center, Memphis, Tennessee, United States of America
| | - Awais Javed
- Boston Baskin Cancer Foundation, Baptist Cancer Center, Memphis, Tennessee, United States of America
| | - Chandrani Mondal
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Emanuele Palescandolo
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Paul Van Hummelen
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Charles Hatton
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Adam J. Bass
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- The Broad Institute, Cambridge, Massachusetts, United States of America
| | - Sung Min Chun
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Deuk Chae Na
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Tae-Im Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Se Jin Jang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Raymond U. Osarogiagbon
- Boston Baskin Cancer Foundation, Baptist Cancer Center, Memphis, Tennessee, United States of America
| | - William C. Hahn
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- The Broad Institute, Cambridge, Massachusetts, United States of America
| | - Matthew Meyerson
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- The Broad Institute, Cambridge, Massachusetts, United States of America
| | - Levi A. Garraway
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- The Broad Institute, Cambridge, Massachusetts, United States of America
| | - Laura E. MacConaill
- Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America
- The Broad Institute, Cambridge, Massachusetts, United States of America
- * E-mail:
| |
Collapse
|
|
16
|
Lumpkins C, Cupertino P, Young K, Daley C, Yeh H, Greiner K. Racial/Ethnic Variations in Colorectal Cancer Screening Self-Efficacy, Fatalism and Risk Perception in a Safety-Net Clinic Population: Implications for Tailored Interventions. ACTA ACUST UNITED AC 2013; 3. [PMID: 24244894 DOI: 10.4172/2161-0711.1000196] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Ethnic and racial minority groups in the U.S. receive fewer colorectal cancer (CRC) screening tests and are less likely to be up-to-date with CRC screening than the population as a whole. Access, limited awareness of CRC and barriers may, in part, be responsible for inhibiting widespread adoption of CRC screening among racial and ethnic minority groups. The purpose of this study was to examine the role of self-efficacy, fatalism and CRC risk perception across racial and ethnic groups in a diverse sample. This study was a cross-sectional analysis from baseline measures gathered on a group of patients recruited into a trial to track colorectal cancer screening in underserved adults over 50. Out of 470 Participants, 42% were non-Hispanic; 27% Hispanic and 28% non-Hispanic White. Hispanic and non-Hispanic Blacks were more likely to have fatalistic beliefs about CRC than non-Hispanic Whites. Non-Hispanic Blacks perceived higher risk of getting colon cancer. Self-efficacy for completing CRC screening was higher among Non-Hispanic Blacks than among Hispanics. Racial and ethnic differences in risk perceptions, fatalism and self-efficacy should be taken into consideration in future CRC interventions with marginalized and uninsured populations.
Collapse
Affiliation(s)
- Cy Lumpkins
- Center Department of Family Medicine, University of Kansas Medical Center, Kansas City, Kansas, 66160, USA
| | | | | | | | | | | |
Collapse
|
|
17
|
Sylvester BE, Huo D, Khramtsov A, Zhang J, Smalling RV, Olugbile S, Polite BN, Olopade OI. Molecular analysis of colorectal tumors within a diverse patient cohort at a single institution. Clin Cancer Res 2011; 18:350-9. [PMID: 22114137 DOI: 10.1158/1078-0432.ccr-11-1397] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE African American colorectal cancer patients have worse survival outcomes than Caucasian patients. To determine whether differences exist in the molecular mechanisms driving colorectal cancer between African Americans and Caucasians, we characterized patient tumors from a single institution by assessing genetic alterations involved in colorectal cancer progression and response to treatment. EXPERIMENTAL DESIGN We retrospectively examined 448 African Americans and Caucasians diagnosed with colorectal cancer at The University of Chicago Medical Center between 1992 and 2002. Microsatellite instability (MSI) status was determined by genotyping the BAT25, BAT26, BAT40, D5S346, and BAX loci. Mutations in KRAS codons 12 and 13 and BRAF codon 600 were identified by direct sequencing. MSI and detected mutations were correlated with clinicopathologic features. RESULTS Overall, no difference existed in MSI or BRAF mutation frequencies between African Americans and Caucasians. However, African Americans with microsatellite stable (MSS)/MSI-low (MSI-L) tumors had a higher proportion of KRAS mutations than Caucasians (34% vs. 23%, P = 0.048) that was isolated to proximal colon cancers and primarily driven by mutations in codon 13. There was no racial difference in receipt of chemotherapy, but African Americans with MSS/MSI-L tumors had a 73% increased risk of death over Caucasians that could not be explained by known prognostic factors. CONCLUSIONS The significantly higher risk of death among African Americans with MSS/MSI-L tumors may be related to differences in the distribution of factors influencing response to standard therapies. These data underscore the need for further research into the molecular mechanisms driving colorectal cancer progression in underserved and understudied populations.
Collapse
Affiliation(s)
- Brooke E Sylvester
- Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Ethnic disparities are reduced in VA colon cancer patients. Am J Surg 2011; 200:636-9. [PMID: 21056144 DOI: 10.1016/j.amjsurg.2010.07.020] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Revised: 07/07/2010] [Accepted: 07/07/2010] [Indexed: 01/07/2023]
Abstract
BACKGROUND Inequalities in access to care have been hypothesized to be the cause of ethnic disparities in colon cancer. The aim of this study was to determine if ethnic disparities in the outcomes of colon cancer patients exist in a system with equal access. METHODS A review of 214 consecutive patients who underwent elective colon resection for adenocarcinoma at 1 institution was conducted. Statistical analysis was performed using independent t tests and χ² tests. The Kaplan-Meier method was used for survival estimates. RESULTS Of the 214 patients who underwent colon cancer resection, 38% (n = 82) were African American, while 62% (n = 132) were Caucasian. There was no significant difference in the stage of disease at presentation and between the mean times from diagnosis to surgical resection for African American and Caucasian patients. Also, there were no differences in survival. CONCLUSION There does not appear to be a disparity in outcomes for colon cancer patients where equal access to medical care exists. This is based on findings of equal stages at presentation, time to referral, and survival among groups.
Collapse
|
|
19
|
Quality and safety of screening colonoscopies performed by primary care physicians with standby specialist support. Med Care 2010; 48:703-9. [PMID: 20613663 DOI: 10.1097/mlr.0b013e3181e358a3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Expanding the population's access to colonoscopy screening can reduce colorectal cancer disparities. Innovative strategies are needed to address the prevailing 50% colonoscopy screening gap, partly attributable to inadequate specialist workforce. This study examined the quality of colonoscopies by primary care physicians (PCPs) with standby specialist support at a licensed ambulatory surgery center. METHODS Retrospective data on 10,958 consecutive colonoscopies performed by 51 PCPs on 9815 patients from October 2002 to November 2007 were used to calculate the rates of cecal intubation, detection of polyps, adenomas, advanced neoplasia and cancer, adverse events, and time taken for endoscope insertion and withdrawal. The center's protocol requires a 2-person technique (using a trained technician), polyp search and removal during both scope insertion and withdrawal, and onsite expert always available for rescue assistance (either navigational or therapeutic). FINDINGS Mean patient age was 58.3 (+/-10.9) years, 48.0% were male, and 48.1% African-American. The cecal intubation rate was 98.1%, polyp detection rate 63.1%, hyperplastic polyp 27.5%, adenoma 29.9%, advanced neoplasia 5.7%, cancer 0.63%, major adverse events 0.06% (including 2 perforations; no death). Mean insertion and withdrawal times were 14.4 (+/-9.3) and 10.9 (+/-6.8) minutes, respectively; 13.2 (+/-8.6) and 8.0 (+/-4.5) minutes without polyps found, and 15.1 (+/-9.6) and 12.5 (+/-7.3) minutes when > or =1 polyp was found. CONCLUSIONS In the largest published study of PCP-performed colonoscopies with standby specialist support, we observed performance quality indicators and lesion detection rates that are comparable to documented rates for experienced gastroenterologists. Systems that use PCPs with specialist backup support enable high-quality colonoscopy performance by PCPs.
Collapse
|
|
20
|
Carroll WR, Kohler CL, Carter VL, Hannon L, Skipper JB, Rosenthal EL. Barriers to early detection and treatment of head and neck squamous cell carcinoma in African American men. Head Neck 2010; 31:1557-62. [PMID: 19431197 DOI: 10.1002/hed.21125] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND African Amercians afflicted with head and neck squamous cell carcinoma (HNSCC) have a strikingly worse survival than do whites. One apparent cause is an advanced stage of presentation in African Americans. This study was designed to identify barriers to early treatment among African American men. METHODS Twenty-four African American male HNSCC survivors completed structured interviews. Interviewers elicited the participants' experiences from symptom recognition to receiving definitive care. RESULTS Most participants were seen with advanced-stage HNSCC. Overall, 10% experienced barriers to obtaining early medical care, though 30% were hesitant to seek care due to perceived barriers. Definitive treatment began for 81% within 3 months of initial care seeking. CONCLUSION Once participants sought care, most of them received definitive treatment within a reasonable time frame. To explain the advanced stage at presentation, either tumor growth rate was extremely rapid or participants sought care when the tumor was quite advanced. The themes suggested by this elicitation study require further validation.
Collapse
Affiliation(s)
- William R Carroll
- Division of Otolaryngology, University of Alabama, Birmingham, Alabama, USA.
| | | | | | | | | | | |
Collapse
|
|
21
|
Manne U, Shanmugam C, Katkoori VR, Bumpers HL, Grizzle WE. Development and progression of colorectal neoplasia. Cancer Biomark 2010; 9:235-65. [PMID: 22112479 PMCID: PMC3445039 DOI: 10.3233/cbm-2011-0160] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A variety of genetic and molecular alterations underlie the development and progression of colorectal neoplasia (CRN). Most of these cancers arise sporadically due to multiple somatic mutations and genetic instability. Genetic instability includes chromosomal instability (CIN) and microsatellite instability (MSI), which is observed in most hereditary non-polyposis colon cancers (HNPCCs) and accounts for a small proportion of sporadic CRN. Although many biomarkers have been used in the diagnosis and prediction of the clinical outcomes of CRNs, no single marker has established value. New markers and genes associated with the development and progression of CRNs are being discovered at an accelerated rate. CRN is a heterogeneous disease, especially with respect to the anatomic location of the tumor, race/ethnicity differences, and genetic and dietary interactions that influence its development and progression and act as confounders. Hence, efforts related to biomarker discovery should focus on identification of individual differences based on tumor stage, tumor anatomic location, and race/ethnicity; on the discovery of molecules (genes, mRNA transcripts, and proteins) relevant to these differences; and on development of therapeutic approaches to target these molecules in developing personalized medicine. Such strategies have the potential of reducing the personal and socio-economic burden of CRNs. Here, we systematically review molecular and other pathologic features as they relate to the development, early detection, diagnosis, prognosis, progression, and prevention of CRNs, especially colorectal cancers (CRCs).
Collapse
Affiliation(s)
- Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
| | | | | | | | | |
Collapse
|
|
22
|
Abstract
With the increasing use of individualized medical care (personalized medicine) in treating and managing patients with cancer, the utilization of biomarkers in selecting and tailoring such medical approaches also is increasing and becoming more important. Specifically, many therapies are effective against only a subgroup of a specific type of tumors and exposing patients with different non-responsive subgroups of the same tumor to ineffective therapies, not only exposes these patients needlessly to acute and chronic side effects of the therapy, but also adds to the costs of medical care. For example, the Oncotype Dx test for estrogen receptor positive tumors that are node negative has been used to identify low risk tumors for which surgery alone is an adequate therapy. Biomarkers may be used to aid in multiple aspects of medical care related to cancer, including early detection, diagnosis, risk assessment, as well as in predicting the aggressiveness of cancers (i.e., prognosis) and predicting the therapeutic efficacy of treatments (i.e., prediction). Biomarkers may be also used as surrogate endpoints to aid in evaluating therapies and preventive approaches. Types of biomarkers vary greatly and include histopathologic appearance, stage of the lesion, quantitative morphologic features, size of the lesion, metastatic pattern and extent of metastasis, as well as imaging and molecular features. The types of measurements of biomarkers also vary; for example, molecular features can be measured at the DNA, mRNA or protein levels as well as at regulatory levels (e.g., microRNA). The usefulness of each biomarker is limited by its sensitivity and specificity in fulfilling its role (e.g., in early detection) and the requirements of sensitivity and specificity to accomplish specific tasks are affected by multiple variables. For example, both very high specificity and sensitivity of a test are required to screen a population with a low prevalence of a specific tumor. The goal of this manuscript is to introduce the reader to how biomarkers may be used and the limitations on the uses of biomarkers in translational research.
Collapse
Affiliation(s)
- William E Grizzle
- Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
| | | | | |
Collapse
|
|
23
|
Murphy MM, Tseng JF, Shah SA. Disparities in cancer care: an operative perspective. Surgery 2009; 147:733-7. [PMID: 19962161 DOI: 10.1016/j.surg.2009.10.050] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Accepted: 10/15/2009] [Indexed: 12/27/2022]
Abstract
BACKGROUND Health disparities in cancer care have been described and stem from a complex interplay of patient, provider, and instutional factors. METHODS A review of the literature describing disparities in aspects of cancer care was performed. RESULTS Disparities in outcomes including overall survival for minority populations have been demonstrated to exist for race, age, and socioeconomic status. CONCLUSION Disparities in cancer care and outcomes clearly exist for many poorly understood reasons. After a diagnosis of cancer, barriers to care may develop at multiple points along the course of the patient's disease.
Collapse
Affiliation(s)
- Melissa M Murphy
- Surgery Outcomes Analysis & Research, Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, S6-432, Worcester, MA 01655, USA
| | | | | |
Collapse
|
|
24
|
Ezzeldin HH, Acosta EP, Mattison LK, Fourie J, Modak A, Diasio RB. (13)C-5-FU breath test current status and future directions: a comprehensive review. J Breath Res 2009; 3:047002. [PMID: 21386199 DOI: 10.1088/1752-7155/3/4/047002] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Breath tests (BTs) represent a safe non-invasive alternative strategy that could provide valuable diagnostic information in conditions like fat malabsorption, carbohydrate (lactose and fructose) malabsorption, liver dysfunction, impaired gastric emptying, abnormal small bowel transit time, small intestinal bacterial overgrowth and Helicobacter pylori infection. To date, despite the availability of a number of breath tests, only three have gained approval by the FDA for application in a clinical setting ((13)C-urea breath test for the detection of H. pylori; NO breath test for monitoring asthma and alkane breath test for heart transplant rejection). Unfortunately, none of these tests investigate cancer patients or response to cancer chemotherapy. Several years ago it was realized that the presence of a reliable non-invasive approach could assist in the detection of patients at risk of developing severe life-threatening toxicities prior to the administration of fluoropyrimidines (e.g. 5-FU) or related cancer chemotherapy. 5-FU toxicity results mainly from deficient uracil catabolism. This review discusses the development of a BT that utilizes an orally administered pyrimidine ([2-(13)C]-uracil) which is metabolized via the same catabolic pathway as 5-FU. This ([2-(13)C]-uracil) breath test could provide a valuable addition to the patients' standard of care.
Collapse
Affiliation(s)
- Hany H Ezzeldin
- Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
| | | | | | | | | | | |
Collapse
|
|
25
|
Katkoori VR, Jia X, Shanmugam C, Wan W, Meleth S, Bumpers H, Grizzle WE, Manne U. Prognostic significance of p53 codon 72 polymorphism differs with race in colorectal adenocarcinoma. Clin Cancer Res 2009; 15:2406-16. [PMID: 19339276 DOI: 10.1158/1078-0432.ccr-08-1719] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE Several studies have examined the prognostic value of the codon 72 polymorphism of the p53 gene in colorectal adenocarcinoma, but none have addressed patient race/ethnicity. Therefore, this study assessed the prognostic value of this polymorphism in African American and Caucasian colorectal adenocarcinoma patients separately. EXPERIMENTAL DESIGN Colorectal adenocarcinomas from 137 African Americans and 236 non-Hispanic Caucasians were assessed for p53 mutations and genotyped for the codon 72 polymorphism. The phenotypes were correlated with p53 mutational status, clinicopathologic features, and patient survival using the chi(2) test and Kaplan-Meier and Cox regression models. RESULTS The incidence of p53 mutations was similar in African American and Caucasian patients (50% versus 54%, respectively); however, the homozygous Pro72 allele frequency was higher in African Americans (17%) as compared with Caucasians (7%). In contrast, the homozygous Arg72 allele frequency was higher in Caucasians (36%) than in African Americans (19%). In African Americans but not Caucasians, the Pro/Pro phenotype significantly correlated with a higher incidence of missense p53 mutations and with nodal metastasis. African Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality (log-rank P = 0.005 versus. P = 0.886) and risk of death due to colorectal adenocarcinoma (hazard ratio, 2.15; 95% confidence interval, 1.02-4.53 versus hazard ratio, 1.60; 95% confidence interval, 0.69-3.18) than those with the phenotype Arg/Arg or Arg/Pro. CONCLUSIONS The higher frequency of the Pro/Pro phenotype of p53 in African American patients with colorectal adenocarcinoma is associated with an increased incidence of p53 mutations, with advanced tumor stage, and with short survival.
Collapse
Affiliation(s)
- Venkat R Katkoori
- Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-7331, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Yan B, Noone AM, Yee C, Banerjee M, Schwartz K, Simon MS. Racial differences in colorectal cancer survival in the Detroit Metropolitan Area. Cancer 2009; 115:3791-800. [PMID: 19598220 DOI: 10.1002/cncr.24408] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Colorectal carcinoma is the second most common cause of cancer death with African Americans having lower survival compared with White Americans. The purpose of this study was to investigate the effect of demographics, clinical factors, and socioeconomic status (SES) on racial disparities in colorectal cancer survival in the Detroit Metropolitan Area. METHODS The study population included 9078 individuals with primary invasive colorectal cancer identified between 1988 and 1992 through the Surveillance, Epidemiology, and End Results (SEER) program. Demographics, clinical information, and survival were obtained through SEER. SES was categorized using occupation, educational level, and poverty status at the census tract level. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare overall survival by race. RESULTS African Americans were more likely to be diagnosed with stage IV disease (P < .001), and to reside within poor census tracts (P < .001) compared with White Americans. Unadjusted analysis showed that African Americans had a significantly higher risk of death compared with their White American counterparts (hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.07-1.20). After adjusting for age, marital status, sex, SES group, TNM stage, and treatment, race was no longer significantly associated with overall survival (HR, 1.00; 95% CI, 0.92-1.09). Similar results were seen with colorectal cancer-specific survival. CONCLUSIONS Racial disparities in colorectal cancer survival dissipate after adjusting for other demographic and clinical factors. These results can potentially affect medical guidelines regarding screening and treatment, and possibly influence public health policies that can have a positive impact on equalizing racial differences in access to care.
Collapse
Affiliation(s)
- Ben Yan
- Department of Internal Medicine, Henry Ford Hospital and Medical Center, Detroit, Michigan, USA
| | | | | | | | | | | |
Collapse
|
|
27
|
Ashktorab H, Nouraie M, Hosseinkhah F, Lee E, Rotimi C, Smoot D. A 50-year review of colorectal cancer in African Americans: implications for prevention and treatment. Dig Dis Sci 2009; 54:1985-90. [PMID: 19554449 DOI: 10.1007/s10620-009-0866-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2008] [Accepted: 05/19/2009] [Indexed: 01/08/2023]
Abstract
BACKGROUND African-Americans (AA) have the highest rate of colorectal cancer (CRC) incidence and mortality in the US. CRC in AA is more advanced and right-sided. Although screening has been shown to reduce mortality from CRC in the general US population, AA continue to experience a disproportionately higher CRC death compared to other ethnic groups. This study aimed at assessing the trend of CRC in AA, focusing on the changing pattern of in situ tumors in this ethnic group and how observed trends may guide current and future preventive and treatment strategies. MATERIALS AND METHODS All pathologic reports from 1959 to 2006 in Howard University Hospital (n = 150,000) were reviewed manually. The pathology reports showing colorectal cancer were carefully reviewed and selected by a GI pathologist. Intraepithelial or intramucosal carcinomas were diagnosed as in situ carcinoma. Reviewed pathological information were entered into Microsoft Excel and checked for duplication and missing data. Differences in situ and advanced cancer by sex, histology, location, and years of diagnosis were assessed by Chi-square test. RESULTS A total of 1,753 CRC cases were diagnosed in this period. About 56% of the cases were female and 51% of the tumors were left-sided. Mean (SD) age was 66 (13) years. The frequency of in situ tumor was 5.8% in this period. There was no statistically significant difference between in situ and advance tumor by age, sex, and tumor location. The rate of in situ tumor peaked in the 1990s at 8.5% (P = 0.0001). We observed a decade-to-decade increasing rate of right-sided tumors, which started at 36% in the period 1959-1970 and peaked in the period of 2001-2006 at 60% (P = 0.0001). CONCLUSIONS The recent increasing number of advanced and right-sided tumor in our study is concordant with SEER data and has great importance in developing CRC prevention and treatment strategies for AA population.
Collapse
Affiliation(s)
- Hassan Ashktorab
- Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC 20060, USA.
| | | | | | | | | | | |
Collapse
|
|
28
|
Dimou A, Syrigos KN, Saif MW. Disparities in colorectal cancer in African-Americans vs Whites: Before and after diagnosis. World J Gastroenterol 2009; 15:3734-43. [PMID: 19673013 PMCID: PMC2726450 DOI: 10.3748/wjg.15.3734] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
There are differences between African-American and white patients with colorectal cancer, concerning their characteristics before and after diagnosis. Whites are more likely to adhere to screening guidelines. This is also the case among people with positive family history. Colorectal cancer is more frequent in Blacks. Studies have shown that that since 1985, colon cancer rates have dipped 20% to 25% for Whites, while rates have gone up for African-American men and stayed the same for African-American women. Overall, African-Americans are 38% to 43% more likely to die from colon cancer than are Whites. Furthermore, it seems that there is an African-American predominance in right-sited tumors. African Americans tend to be diagnosed at a later stage, to suffer from better differentiated tumors, and to have worse prognosis when compared with Whites. Moreover, less black patients receive adjuvant chemotherapy for resectable colorectal cancer or radiation therapy for rectal cancer. Caucasians seem to respond better to standard chemotherapy regimens than African-Americans. Concerning toxicity, it appears that patients of African-American descent are more likely to develop 5-FU toxicity than Whites, possibly because of their different dihydropyridine dehydrogenase status. Last but not least, screening surveillance seems to be higher among white than among black long-term colorectal cancer survivors. Socioeconomic and educational status account for most of these differences whereas little evidence exists for a genetic contribution in racial disparity. Understanding the nature of racial differences in colorectal cancer allows tailoring of screening and treatment interventions.
Collapse
|
|
29
|
Abstract
African Americans are disproportionately burdened with colorectal cancer. Although incidence and mortality rates have declined in the past two decades, the disparity in health outcomes has progressively increased. This comprehensive review examines the existing literature regarding racial disparities in colorectal cancer screening, stage at diagnosis, and treatment to determine if differences exist in the quality of care delivered to African Americans. A comprehensive review of relevant literature was performed. Two databases (EBSCOHOST Academic Search Premier and Scopus) were searched from 2000 to 2007. Articles that assessed racial disparities in colorectal cancer screening, stage of disease at diagnosis, and treatment were selected. The majority of studies identified examined colorectal cancer screening outcomes. Although racial disparities in screening have diminished in recent years, African American men and women continue to have higher colorectal cancer incidence and mortality rates and are diagnosed at more advanced stages. Several studies regarding stage of disease at diagnosis identified socioeconomic status (SES) and health insurance status as major determinants of disparity. However, some studies found significant racial disparities even after controlling for these factors. Racial disparities in treatment were also found at various diagnostic stages. Many factors affecting disparities between African Americans and Whites in colorectal cancer incidence and mortality remain unexplained. Although the importance of tumor biology, genetics, and lifestyle risk factors have been established, prime sociodemographic factors need further examination to understand variances in the care of African Americans diagnosed with colorectal cancer.
Collapse
|
|
30
|
Le H, Ziogas A, Lipkin SM, Zell JA. Effects of Socioeconomic Status and Treatment Disparities in Colorectal Cancer Survival. Cancer Epidemiol Biomarkers Prev 2008; 17:1950-62. [PMID: 18708384 DOI: 10.1158/1055-9965.epi-07-2774] [Citation(s) in RCA: 163] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Hoa Le
- Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, School of Medicine, University of California at Irvine, Irvine, CA 92697, USA
| | | | | | | |
Collapse
|
|
31
|
Byers TE, Wolf HJ, Bauer KR, Bolick-Aldrich S, Chen VW, Finch JL, Fulton JP, Schymura MJ, Shen T, Van Heest S, Yin X. The impact of socioeconomic status on survival after cancer in the United States. Cancer 2008; 113:582-91. [DOI: 10.1002/cncr.23567] [Citation(s) in RCA: 312] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
|
|
32
|
Gao R, Price DK, Sissung T, Reed E, Figg WD. Ethnic disparities in Americans of European descent versus Americans of African descent related to polymorphic ERCC1, ERCC2, XRCC1, and PARP1. Mol Cancer Ther 2008; 7:1246-50. [PMID: 18483312 PMCID: PMC3571703 DOI: 10.1158/1535-7163.mct-07-2206] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Nucleotide excision repair (NER) and base excision repair (BER) pathways are DNA repair pathways that are important in carcinogenesis and in response to DNA-damaging chemotherapy. ERCC1 and ERCC2 are important molecular markers for NER; XRCC1 and PARP1 are important molecular markers for BER. Functional polymorphisms have been described that are associated with altered expression levels of these genes and with altered DNA repair capability. We assayed genomic DNA from 156 Americans of European descent and 164 Americans of African descent for the allelic frequencies of specific polymorphisms of ERCC1 N118N (500C>T), ERCC1 C8092A, ERCC2 K751Q (2282A>C), XRCC1 R399Q (1301G>A), XRCC1 R194W (685C>T), and PARP1 V762A (2446T>C). Differences were observed between Americans of European descent and Americans of African descent in the allelic frequencies of the ERCC1 N118N polymorphism (P < 0.000001). Differences were also observed between these two ethnic groups for ERCC2 K751Q (P = < 0.006675), XRCC1 R399Q (P < 0.000001), and PARP1 V762A (P = 0.000001). The ERCC1 N118N polymorphic variant that is seen most commonly in Americans of European descent is associated with a measurable reduction in NER function. ERCC1-mediated reduction in NER functionality affects the repair of cisplatin-DNA lesions.
Collapse
Affiliation(s)
- Rui Gao
- Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
- University of Maryland, College Park, MD
| | - Douglas K. Price
- Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Tristan Sissung
- Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Eddie Reed
- Centers for Disease Control and Prevention, Atlanta, GA
| | - William D. Figg
- Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
- Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
- Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| |
Collapse
|
|
33
|
Alexander DD, Waterbor J, Hughes T, Funkhouser E, Grizzle W, Manne U. African-American and Caucasian disparities in colorectal cancer mortality and survival by data source: an epidemiologic review. Cancer Biomark 2008; 3:301-13. [PMID: 18048968 DOI: 10.3233/cbm-2007-3604] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Over the past four decades in the United States, there has been a divergent trend in mortality rates between African-Americans and Caucasians with colorectal cancer (CRC). Rates among Caucasians have been steadily declining, whereas rates among African-Americans have only started a gradual decline in recent years. We reviewed epidemiologic studies of CRC racial disparities between African-Americans and Caucasians, including studies from SEER and population-based cancer registries, Veterans Affairs (VA) databases, healthcare coverage databases, and university and other medical center data sources. Elevated overall and stage-specific risks of CRC mortality and shorter survival for African-Americans compared with Caucasians were reported across all data sources. The magnitude of racial disparities varied across study groups, with the strongest associations observed in university and non-VA hospital-based medical center studies, while an attenuated discrepancy was found in VA database studies. An advanced stage of disease at the time of diagnosis among African-Americans is a major contributing factor to the racial disparity in survival. Several studies, however, have shown that an increased risk of CRC death among African-Americans remains even after controlling for tumor stage at diagnosis, socioeconomic factors, and co-morbidity. Despite advances in treatment, improvements in the standard of care, and increased screening options, racial differences persist in CRC mortality and survival. Therefore, continued research efforts are necessary to disentangle the clinical, social, biological, and environmental factors that constitute the racial disparity. In addition, results across data sources should be considered when evaluating racial differences in cancer outcomes.
Collapse
|
|
34
|
Manne U. Understanding racial differences in colorectal cancer aids in individualized medicine. Future Oncol 2007; 3:235-41. [PMID: 17547516 DOI: 10.2217/14796694.3.3.235] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
|
|
35
|
Lloyd SC, Harvey NR, Hebert JR, Daguise V, Williams D, Scott DB. Racial disparities in colon cancer. Primary care endoscopy as a tool to increase screening rates among minority patients. Cancer 2007; 109:378-85. [PMID: 17123276 DOI: 10.1002/cncr.22362] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Colon cancer is a condition whose far-reaching effects have been well documented nationally and within the state of South Carolina. Fortunately, the disease is amenable to both primary and secondary prevention through screening colonoscopy. Despite the conceptual simplicity of recommending colonoscopy, barriers exist to universal (or even widespread) screening. Currently the infrastructure necessary to achieve screening goals set by the American Cancer Society (ACS), the American College of Gastroenterology (ACG), and the South Carolina Department of Health and Environmental Control (DHEC) has not been established. At current rates of training gastroenterologists, the medical community will not be able to come close to achieving widespread screening. Given the discrepancy between the public health benefit of achieving the goals and the deaths that have occurred because of the resource shortfall, we propose alternative measures to screen the at-risk population for consideration. This need is most acute in the black community, in which where screening rates tend to be lower and polyps have been found to progress more quickly than among white populations. In South Carolina, one model has used primary care physicians as the labor force to provide routine screening colonoscopy for their own patients. This model makes screening much more accessible to minority patients, as the wait is shorter and the cost typically lower. In combination with a faith-based partnership with minority religious organizations, this model has begun to make needed inroads toward addressing the disparities associated with colon cancer. Cancer 2007. (c) 2006 American Cancer Society.
Collapse
Affiliation(s)
- Stephen C Lloyd
- Department of Family Medicine, South Carolina Medical Endoscopy Center and University of South Carolina School of Medicine, Columbia, South Carolina 29201, USA.
| | | | | | | | | | | |
Collapse
|
|
36
|
Chatla C, Jhala NC, Katkoori VR, Alexander D, Meleth S, Grizzle WE, Manne U. Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma. Cancer Biomark 2007; 1:241-50. [PMID: 17192048 PMCID: PMC2667690 DOI: 10.3233/cbm-2005-14-507] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Although decreased or lack of expression of Bcl-2 has been correlated with advanced tumor stage and shortened patient survival in colorectal cancer (CRC), its value in predicting the recurrence has not been well explored. Therefore, we assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues of 92 Stage II and 66 Stage III primary CRCs were evaluated for immunohistochemical expression of Bcl-2. None of these patients received either pre- or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional hazards methods were used to estimate the rates of recurrence and survival according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank test P=0.0015; Hazard Ratio (HR)=3.90, 95%C.I.:1.55-9.77) but not with Stage III CRCs (5-year log-rank test P=0.6058; HR=1.07, 95%C.I.:0.47-2.45) after adjusting for other demographic and clinicopathological features. Furthermore, decreased expression of Bcl-2 was an indicator of short survival in patients with Stage II CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in primary CRCs may serve as a molecular biomarker of high risk of recurrence for Caucasian patients with Stage II CRCs. These findings might be useful in identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the oncologist in designing maximally appropriate therapeutic regimens.
Collapse
Affiliation(s)
- Chakrapani Chatla
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Nirag C. Jhala
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Venkat R. Katkoori
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Dominik Alexander
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Sreelatha Meleth
- Department of Biostatistics and Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - William E. Grizzle
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Corresponding author: Upender Manne, MS., Ph.D., Associate Professor, Department of Pathology, University of Alabama at Birmingham, 523-Kracke Building, 1922, 7th Avenue South, Birmingham, AL, 35294-7331, USA. Tel.: +1 205 934 4276; Fax: +1 205 934 4418; E-mail:
| |
Collapse
|
|
37
|
Mattison LK, Fourie J, Desmond RA, Modak A, Saif MW, Diasio RB. Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians. Clin Cancer Res 2006; 12:5491-5. [PMID: 17000684 DOI: 10.1158/1078-0432.ccr-06-0747] [Citation(s) in RCA: 120] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE African-American patients with colorectal cancer were observed to have increased 5-fluorouracil (5-FU)-associated toxicity (leukopenia and anemia) and decreased overall survival compared with Caucasian patients. One potential source for this disparity may be differences in 5-FU metabolism. Dihydropyrimidine dehydrogenase (DPD), the initial and rate-limiting enzyme of 5-FU catabolism, has previously been shown to have significant interpatient variability in activity. Several studies have linked reduced DPD activity to the development of 5-FU toxicity. Although the distribution of DPD enzyme activity and the frequency of DPD deficiency have been well characterized in the Caucasian population, the distribution of DPD enzyme activity and the frequency of DPD deficiency in the African-American population are unknown. EXPERIMENTAL DESIGN Healthy African-American (n=149) and Caucasian (n=109) volunteers were evaluated for DPD deficiency using both the [2-(13)C]uracil breath test and peripheral blood mononuclear cell DPD radioassay. RESULTS African-Americans showed significantly reduced peripheral blood mononuclear cell DPD enzyme activity compared with Caucasians (0.26+/-0.07 and 0.29+/-0.07 nmol/min/mg, respectively; P=0.002). The prevalence of DPD deficiency was 3-fold higher in African-Americans compared with Caucasians (8.0% and 2.8%, respectively; P=0.07). African-American women showed the highest prevalence of DPD deficiency compared with African-American men, Caucasian women, and Caucasian men (12.3%, 4.0%, 3.5%, and 1.9%, respectively). CONCLUSION These results indicate that African-Americans, particularly African-American women, have significantly reduced DPD enzyme activity compared with Caucasians, which may predispose this population to more 5-FU toxicity.
Collapse
Affiliation(s)
- Lori Kay Mattison
- Division of Clinical Pharmacology and Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA
| | | | | | | | | | | |
Collapse
|
|
38
|
Morris AM, Wei Y, Birkmeyer NJO, Birkmeyer JD. Racial disparities in late survival after rectal cancer surgery. J Am Coll Surg 2006; 203:787-94. [PMID: 17116545 DOI: 10.1016/j.jamcollsurg.2006.08.005] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2006] [Revised: 07/24/2006] [Accepted: 08/02/2006] [Indexed: 11/19/2022]
Abstract
BACKGROUND African-American patients experience higher mortality than Caucasian patients after surgery for most common cancer types. Whether longterm survival after rectal cancer surgery varies by race is less clear. STUDY DESIGN Using 1992 to 2003 Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we examined race and longterm survival among African-American and Caucasian rectal cancer patients undergoing resection. We identified racial differences in patient characteristics, structure, and processes of care. We then assessed mortality using a Cox proportional hazards model, sequentially adding variables to explore the extent to which they attenuated the association between race and mortality. RESULTS African-American patients had a substantially poorer overall survival rate than Caucasian patients did. Five-year survival rates were 41% and 50%, respectively (p < 0.0001). African Americans were younger (p=0.006), more likely to reside in low income areas (p < 0.0001), and had more baseline comorbid disease (p < 0.0001). They were also more likely to be diagnosed emergently (p < 0.001) and with more advanced cancer (p < 0.001). Accounting for demographic and clinical characteristics reduced the mortality difference, although it remained pronounced (hazard ratio=1.13, CI=1.01 to 1.26). African Americans were more likely to be treated by low volume surgeons and less likely to receive adjuvant therapy (48.6% versus 60.9%, p < 0.0001). After adjusting for provider variables, the hazard ratio for mortality by race was additionally attenuated and became statistically nonsignificant (hazard ratio=1.05, CI=0.92 to 1.20). CONCLUSIONS Poorer longterm survival after rectal cancer surgery among African Americans is explained by measurable differences in processes of care and patient characteristics. These data suggest that outcomes disparities could be reduced by strategies targeting earlier diagnosis and increasing adjuvant therapy use among African-American patients.
Collapse
Affiliation(s)
- Arden M Morris
- Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, MI, USA
| | | | | | | |
Collapse
|
|
39
|
Polite BN, Dignam JJ, Olopade OI. Colorectal cancer model of health disparities: understanding mortality differences in minority populations. J Clin Oncol 2006; 24:2179-87. [PMID: 16682737 DOI: 10.1200/jco.2005.05.4775] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
African Americans are more likely to be diagnosed with and die as a result of colorectal cancer than white patients. This review briefly documents these differences and explores the factors that may contribute to advanced stage at diagnosis and reduced survival once African Americans are diagnosed with colorectal cancer. Attention is focused on what is known about the role of socioeconomic status, cancer screening, comorbidities and lifestyle factors, tumor biology and genetics, and the differences in the receipt of and benefit of appropriate therapy. Finally, areas of ongoing and future research and policy initiatives aimed at reducing disparities are discussed.
Collapse
Affiliation(s)
- Blase N Polite
- Section of Hematology-Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
| | | | | |
Collapse
|
|
40
|
Lee JT, Chaloner EJ, Hollingsworth SJ. The role of cardiopulmonary fitness and its genetic influences on surgical outcomes. Br J Surg 2005; 93:147-57. [PMID: 16302176 DOI: 10.1002/bjs.5197] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Abstract
Background
Outcome after major surgery remains poor in some patients. There is an increasing need to identify this cohort and develop strategies to reduce postsurgical morbidity and mortality. Central to outcome is the ability to mount cardiovascular output in response to the increased oxygen demand associated with major surgery.
Methods
A medline search was performed using keywords to identify factors that affect, and genetic influences in, disease and outcome from surgery, and all relevant English language articles published between 1980 and 2005 were retrieved. Secondary references were obtained from key articles.
Results
Preoperative cardiopulmonary exercise testing assesses patient fitness, highlights those at particular risk and, combined with triage to critical care, facilitates significant improvement in surgical outcome. However, genetic factors also influence responses to increased oxygen demand, and some patients are genetically predisposed to mounting increased inflammatory responses, which raise oxygen demand further. Polymorphisms in genes influencing fitness (angiotensin converting enzyme) and immune and inflammatory responses (such as interleukin 6) may associate with surgical outcome.
Conclusions
Development of preoperative screening methods like cardiopulmonary exercise testing and genotype analysis to identify index factors may permit better patient stratification, provide targets for future tailored treatments and so improve surgical outcome.
Collapse
Affiliation(s)
- J T Lee
- Department of Surgery, The Royal Free and University College Medical School, The Middlesex Hospital, Mortimer Street, London W1T 3AA, UK
| | | | | |
Collapse
|
|
41
|
Alexander D, Jhala N, Chatla C, Steinhauer J, Funkhouser E, Coffey CS, Grizzle WE, Manne U. High-grade tumor differentiation is an indicator of poor prognosis in African Americans with colonic adenocarcinomas. Cancer 2005; 103:2163-70. [PMID: 15816050 PMCID: PMC2667688 DOI: 10.1002/cncr.21021] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND To identify the factors that contribute to poorer colon carcinoma survival rates for African Americans compared with Caucasians, the authors evaluated survival differences based on the histologic grade (differentiation) of the tumor. METHODS All 169 African Americans and 229 randomly selected non-Hispanic Caucasians who underwent surgery during 1981-1993 for first primary sporadic colon carcinoma at the University of Alabama at Birmingham or its affiliated Veterans Affairs hospital were included in the current study. None of these patients received presurgery or postsurgery therapies. Recently, the authors reported an increased risk of colon carcinoma death for African Americans in this patient population, after adjustment for stage and other clinicodemographic features. The authors generated Kaplan-Meier survival probabilities according to race and tumor differentiation and multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS There were no differences in the distribution of pathologic tumor stage between racial groups after stratifying by histologic tumor grade. Among patients with high-grade tumors, 54% of African Americans and 21% of Caucasians died within the first year after surgery (P = 0.007). African Americans with high-grade tumors were 3 times (HR = 3.05; 95% CI, 1.32-7.05) more likely to die of colon carcinoma within 5 years postsurgery, compared with Caucasians with high-grade tumors. There were no survival differences by race among patients with low-grade tumors. CONCLUSIONS These findings suggested that poorer survival among African-American patients with adenocarcinomas of the colon may not be attributable to an advanced pathologic stage of disease at diagnosis, but instead may be due to aggressive biologic features like high tumor grades.
Collapse
Affiliation(s)
- Dominik Alexander
- Department of Epidemiology, University of Alabama-Birmingham, Birmingham, Alabama
| | - Nirag Jhala
- Department of Pathology, University of Alabama-Birmingham, Birmingham, Alabama
| | - Chakrapani Chatla
- Department of Pathology, University of Alabama-Birmingham, Birmingham, Alabama
| | - Jon Steinhauer
- Department of Pathology, University of Alabama-Birmingham, Birmingham, Alabama
| | - Ellen Funkhouser
- Department of Epidemiology, University of Alabama-Birmingham, Birmingham, Alabama
| | | | - William E. Grizzle
- Department of Pathology, University of Alabama-Birmingham, Birmingham, Alabama
| | - Upender Manne
- Department of Pathology, University of Alabama-Birmingham, Birmingham, Alabama
| |
Collapse
|
|
42
|
Polite BN, Dignam JJ, Olopade OI. Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites. Med Clin North Am 2005; 89:771-93. [PMID: 15925649 DOI: 10.1016/j.mcna.2005.03.001] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Understanding the differences in the incidence and mortality rate between African Americans and whites with CRC remains a perplexing problem. There is clearly not any one factor that explains the observed differences. Clinicians are just beginning to understand the importance of tumor biology, genetics, and lifestyle risk factors in explaining differences in how CRCs present and how they behave. This holds true regardless of a patient's race, sex, or age. Whether these factors will add disproportionately to the understanding of racial differences in presentation and outcome remains to be seen. Certainly, issues surrounding screening for CRC remain important in understanding the advanced stage of presentation for African Americans. In particular, a better understanding is needed of who is being screened and who is not and why. For example, are higher-risk African Americans being screened and if not what are the reasons for this? Importantly, even if one were able to eliminate the differences in stage at presentation between African Americans and whites, a survival disadvantage, albeit a much smaller one, would likely persist. Clearly, there is a need to understand better why African Americans are not receiving recommended therapy at the same rate as whites. This becomes even more important as the life-prolonging options for treating both localized and metastatic colon cancer continue to multiply. Finally, the apparent greater disparity in outcome for African Americans who have stage II disease should be explored in more detail, because this could have an immediate impact on treatment recommendations. For example, a 23-gene signature was recently found to be predictive of recurrence among patients with Dukes B colon cancer [66]. If this model is validated in further studies, one could look at whether African-American patients are more likely to have this predictive signature. The problem has been clearly defined: a higher incidence of and a higher mortality from CRC for African Americans than whites. The task now becomes to continue to understand the reasons for the disparities and ultimately to come up with workable solutions so that the amazing progress in CRC treatment benefits all groups in this country.
Collapse
Affiliation(s)
- Blase N Polite
- Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USA.
| | | | | |
Collapse
|
|
43
|
Hall SA, Kaufman JS. Postsurgical disparity in survival between African Americans and Caucasians with colonic adenocarcinoma. Cancer 2004; 101:2899; author reply 2900. [PMID: 15494972 DOI: 10.1002/cncr.20702] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
|
|
44
|
|