Grant Number:	5R01CA255318-02 Interpret this number
Primary Investigator:	Warren Andersen, Shaneda
Organization:	University Of Wisconsin-Madison
Project Title:	Understanding the Contribution of Colorectal Cancer Tumor Characteristics to Disparities in Colorectal Cancer Survival
Fiscal Year:	2022

PROJECT ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death among U.S. men and women. Racial disparities in CRC survival exist, where the CRC mortality rate for African Americans is 40% higher than the mortality rate for non-Hispanic white Americans. Evidence suggests there may be racial differences in intrinsic CRC tumor biology. We hypothesize that the molecular profile of CRC tumors is more aggressive on average for African Americans than white Americans, and that these tumor differences contribute to the racial disparity in survival. The overarching goal of the project is to define how the CRC survival disparity experienced by African Americans may be influenced by complex biologic differences in tumor characteristics, measured by molecular subtypes, driver gene status, and clinicopathologic markers. The research plan uses molecular epidemiologic and cancer biology approaches to achieve our study aims by leveraging resources from three established research studies, including CRC tumor tissue data from approximately 420 African American CRC patients and 404 non-Hispanic white CRC patients from the Southern Community Cohort Study, the Black Women’s Health Study, and The Cancer Genome Atlas (TCGA). To fulfill Aim 1, we will characterize CRC tumors from white and African American CRC patients for clinicopathologic markers (anatomic site, stage), microsatellite instability, driver gene status (BRAF, and RAS mutation status), and the recently-defined CRC consensus molecular subtypes. The proposed project will be the first study to define CRC consensus molecular subtypes in African Americans. Bioinformatics approaches will identify novel gene- expression molecular subtypes, measured using RNA-seq, to explore the possibility of detecting molecular subtypes that are more prevalent among African American tumors and that may be linked to CRC prognosis. (Aim 2). Lastly, to fulfill Aim 3, associations will be determined between the abovementioned tumor characteristics and CRC survival, and assessed for differences by race. The scientific impact of the proposed study will be to determine the biological mechanisms contributing to CRC survival disparities experienced by African Americans by uncovering the molecular attributes of the tumors themselves. The results of the study will establish the essential foundation for future interventional studies. Currently, CRC treatment is determined by a combination of molecular factors including stage and the presence of somatic mutations. Emerging CRC therapies may be guided by additional tumor factors such as tumor gene-expression or the presence of other targetable features. The existing limited knowledge of the biologic properties of African American CRCs reduces the prospect that precision medicine will be effective. The proposed study aims to provide data on African American CRC tumor molecular profiles to support subtype-specific treatments and precision health strategies to decrease mortality and reduce racial disparities.




Associations of diabetes and mortality among colorectal cancer patients from the Southern Community Cohort Study.
Authors: Lawler T. , Hibler E. , Walts Z.L. , Giurini L. , Steinwandel M. , Lipworth L. , Murff H.J. , Zheng W. , Warren Andersen S. .
Source: British Journal Of Cancer, 2024-07-19 00:00:00.0; , .
EPub date: 2024-07-19 00:00:00.0.
PMID: 39030444
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Metformin's role in lowering colorectal cancer risk among individuals with diabetes from the Southern Community Cohort Study.
Authors: Lawler T. , Walts Z.L. , Giurini L. , Steinwandel M. , Lipworth L. , Murff H.J. , Zheng W. , Warren Andersen S. .
Source: Cancer Epidemiology, 2024 Jun; 90, p. 102566.
EPub date: 2024-03-21 00:00:00.0.
PMID: 38518387
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"There is no expiration date": a qualitative analysis using the Social Cognitive Theory to identify factors influencing physical activity among adults living with advanced cancer.
Authors: Agnew M. , Cadmus-Bertram L. , Kwekkeboom K. , Gorzelitz J. , Ruzicka M. , Gangnon R. , Andersen S.W. .
Source: Supportive Care In Cancer : Official Journal Of The Multinational Association Of Supportive Care In Cancer, 2024-03-22 00:00:00.0; 32(4), p. 242.
EPub date: 2024-03-22 00:00:00.0.
PMID: 38514490
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Race- and Gender-Specific Associations between Neighborhood-Level Socioeconomic Status and Body Mass Index: Evidence from the Southern Community Cohort Study.
Authors: Giurini L. , Lipworth L. , Murff H.J. , Zheng W. , Warren Andersen S. .
Source: International Journal Of Environmental Research And Public Health, 2023-11-30 00:00:00.0; 20(23), .
EPub date: 2023-11-30 00:00:00.0.
PMID: 38063552
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Type 2 Diabetes and Colorectal Cancer Risk.
Authors: Lawler T. , Walts Z.L. , Steinwandel M. , Lipworth L. , Murff H.J. , Zheng W. , Warren Andersen S. .
Source: Jama Network Open, 2023-11-01 00:00:00.0; 6(11), p. e2343333.
EPub date: 2023-11-01 00:00:00.0.
PMID: 37962884
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Racial disparities in colorectal cancer clinicopathological and molecular tumor characteristics: a systematic review.
Authors: Lawler T. , Parlato L. , Warren Andersen S. .
Source: Cancer Causes & Control : Ccc, 2023-09-09 00:00:00.0; , .
EPub date: 2023-09-09 00:00:00.0.
PMID: 37688643
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Pre-diagnostic 25-hydroxyvitamin D in association with cancer specific- and all-cause mortality among low income, non-Hispanic Black Americans with colorectal cancer.
Authors: Lawler T.P. , Khankari N.K. , Shu X.O. , Steinwandel M. , Cai Q. , Jurutka P.W. , Zheng W. , Warren Andersen S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2023-05-31 00:00:00.0; , .
EPub date: 2023-05-31 00:00:00.0.
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Associations between serum vitamin D biomarkers and tumor expression of Ki67, p53, and COX-2 in colorectal cancer cases from the Southern Community Cohort Study.
Authors: Lawler T. , Su T. , Cai Q. , Steinwandel M.D. , Zheng W. , Blot W.J. , Warren Andersen S. .
Source: The Journal Of Steroid Biochemistry And Molecular Biology, 2023 Jan; 225, p. 106201.
EPub date: 2022-10-06 00:00:00.0.
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Associations between Folate and Alcohol Consumption with Colorectal Tumor Ki67 Expression in the Southern Community Cohort Study.
Authors: Lawler T. , Su T. , Cai Q. , Steinwandel M.D. , Zheng W. , Warren Andersen S. .
Source: Nutrition And Cancer, 2023; 75(4), p. 1211-1222.
EPub date: 2023-03-12 00:00:00.0.
PMID: 36908193
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Reduced racial disparity in receipt of optimal locoregional treatment for women with early-stage breast cancer.
Authors: Nadeem H. , Romley J.A. , Warren Andersen S. .
Source: Plos One, 2023; 18(9), p. e0291025.
EPub date: 2023-09-01 00:00:00.0.
PMID: 37656742
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Sociocultural Factors, Access to Healthcare, and Lifestyle: Multifactorial Indicators in Association with Colorectal Cancer Risk.
Authors: Warren Andersen S. , Zheng W. , Steinwandel M. , Murff H.J. , Lipworth L. , Blot W.J. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2022-09-01 00:00:00.0; 15(9), p. 595-603.
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