Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians

Hiroshi Y Yamada; Chao Xu; Kenneth L Jones; Philip H O'Neill; Madka Venkateshwar; Srikanth Chiliveru; Hyung-Gyoon Kim; Mark Doescher; Katherine T Morris; Upender Manne; Chinthalapally V Rao

doi:10.1038/s41698-023-00433-5

Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians

NPJ Precis Oncol. 2023 Aug 19;7(1):79. doi: 10.1038/s41698-023-00433-5.

Authors

Hiroshi Y Yamada^{1

2}, Chao Xu³, Kenneth L Jones⁴, Philip H O'Neill⁵, Madka Venkateshwar^{6

7}, Srikanth Chiliveru^{6

7}, Hyung-Gyoon Kim⁸, Mark Doescher⁹, Katherine T Morris¹⁰, Upender Manne¹¹, Chinthalapally V Rao^{12

13

14}

Affiliations

¹ Department of Internal Medicine, Hematology/Oncology Section, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA. Hiroshi-Yamada@ouhsc.edu.
² Center for Cancer Prevention and Drug Development, Stephenson Cancer Center, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA. Hiroshi-Yamada@ouhsc.edu.
³ Department of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
⁴ Department of Cell Biology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
⁵ Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
⁶ Department of Internal Medicine, Hematology/Oncology Section, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
⁷ Center for Cancer Prevention and Drug Development, Stephenson Cancer Center, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
⁸ Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Community Outreach and Engagement, Stephenson Cancer Center, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
¹⁰ Department of Surgery, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
¹¹ Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. upendermanne@uabmc.edu.
¹² Department of Internal Medicine, Hematology/Oncology Section, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA. CV-Rao@ouhsc.edu.
¹³ Center for Cancer Prevention and Drug Development, Stephenson Cancer Center, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA. CV-Rao@ouhsc.edu.
¹⁴ VA Medical Center, Oklahoma City, OK, USA. CV-Rao@ouhsc.edu.

Abstract

In the US, the majority of cancer samples analyzed are from white people, leading to biases in racial and ethnic treatment outcomes. Colorectal cancer (CRC) incidence and mortality rates are high in Alabama African Americans (AAs) and Oklahoma American Indians (AIs). We hypothesized that differences between racial groups may partially explain these disparities. Thus, we compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1). Therefore, targeting strategies designed for white CRC patients may be less effective for AAs/AIs. These findings illustrate needs to develop optimized interventions to overcome racial CRC disparities.

Abstract

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