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Racial disparities in colorectal cancer clinicopathological and molecular tumor characteristics: a systematic review

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Abstract

Purpose

African Americans have the highest colorectal cancer (CRC) mortality of all racial groups in the USA, which may relate to differences in healthcare access or advanced stage at diagnosis. Recent evidence indicates that differences in tumor characteristics may also underlie disparities in mortality. To highlight recent findings and areas for investigation, we completed the first systematic review of racial disparities in CRC tumor prognostic markers, including clinicopathological markers, microsatellite instability (MSI), oncogene mutations, and novel markers, including cancer stem cells and immune markers.

Methods

Relevant studies were identified via PubMed, limited to original research published within the last 10 years. Ninety-six articles were identified that compared the prevalence of mortality-related CRC tumor characteristics in African Americans (or other African ancestry populations) to White cases.

Results

Tumors from African ancestry cases are approximately 10% more likely to contain mutations in KRAS, which confer elevated mortality and resistance to epidermal growth factor receptor inhibition. Conversely, African Americans have approximately 50% lower odds for BRAF-mutant tumors, which occur less frequently but have similar effects on mortality and therapeutic resistance. There is less consistent evidence supporting disparities in mutations for other oncogenes, including PIK3CA, TP53, APC, NRAS, HER2, and PTEN, although higher rates of PIK3CA mutations and lower prevalence of MSI status for African ancestry cases are supported by recent evidence. Although emerging evidence suggests that immune markers reflecting anti-tumor immunity in the tumor microenvironment may be lower for African American cases, there is insufficient evidence to evaluate disparities in other novel markers, cancer stem cells, microRNAs, and the consensus molecular subtypes.

Conclusion

Higher rates of KRAS-mutant tumors in in African Americans may contribute to disparities in CRC mortality. Additional work is required to understand whether emerging markers, including immune cells, underlie the elevated CRC mortality observed for African Americans.

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Data availability

All studies cited in this review are publicly available.

Abbreviations

AACR:

American Association for Cancer Research

APC:

Adenomatous polyposis coli

AJCC:

American Joint Committee on Cancer

CIMP:

CpG island methylator phenotype

CIN:

Chromosomal instability

CMS:

Consensus molecular subtypes

CRC:

Colorectal cancer

EGFR:

Epidermal growth factor receptor

FDA:

Food and Drug Administration

HER2:

Human epidermal growth factor receptor 2

JAK-STAT:

Janus kinase and signal transducer and activator of transcription

MAPK:

Mitogen-activated protein kinase

MeSH:

Medical subject heading

MHC:

Major histocompatibility complex

miRNA:

MicroRNA

MMR:

Mismatch repair

mRNA:

Messenger RNA

MSI:

Microsatellite instability

MSS:

Microsatellite stable

PDC:

Poorly differentiated cluster

PD-1:

Programmed death protein 1

PD-L1:

Programmed death-ligand 1

PI3K:

Phosphoinositide 3-kinase

PIP2/3:

Phosphatidylinositol 4,5-bi/triphosphate

PTEN:

Phosphatase and tensin homologue

SEER:

Surveillance, Epidemiology, and End Results program

SRCC:

Signet ring cell carcinoma

TIL:

Tumor-infiltrating lymphocytes

TNM:

Tumor, node, metastasis

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Funding

This work was supported by the National Cancer Institute of the National Institutes of Health [NIH/NCI] under grants R00 CA207848 and R01 CA255318.

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  1. Thomas Lawler and Lisa Parlato have equally contributed to this work.

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  1. Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA

    Thomas Lawler & Shaneda Warren Andersen

  2. School of Medicine and Public Health, Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA

    Lisa Parlato & Shaneda Warren Andersen

  3. University of Wisconsin-Madison, Suite 1007B, WARF, 610 Walnut Street, Madison, WI, 53726, USA

    Shaneda Warren Andersen

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LP and SWA conceptualized the project and designed the literature review. LP and TL performed the literature review. LP and TL completed the initial draft of the manuscript. All authors completed revisions to create the final draft of the manuscript.

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Lawler, T., Parlato, L. & Warren Andersen, S. Racial disparities in colorectal cancer clinicopathological and molecular tumor characteristics: a systematic review. Cancer Causes Control 35, 223–239 (2024). https://doi.org/10.1007/s10552-023-01783-y

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