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Review
. 2024 Nov 21;16(23):3903.
doi: 10.3390/cancers16233903.

WNT and TGF-Beta Pathway Alterations in Early-Onset Colorectal Cancer Among Hispanic/Latino Populations

Cecilia Monge  1 , Brigette Waldrup  2 , Francisco G Carranza  2 , Enrique Velazquez-Villarreal  2   3
Affiliations
Review

WNT and TGF-Beta Pathway Alterations in Early-Onset Colorectal Cancer Among Hispanic/Latino Populations

Cecilia Monge et al. Cancers (Basel). .

Abstract

Background/objectives: One of the fastest-growing minority groups in the U.S. is the Hispanic/Latino population. Recent studies have shown how this population is being disproportionately affected by early-onset colorectal cancer (CRC). Compared to corresponding non-Hispanic White (NHW) patients, Hispanic/Latino patients have both higher incidence of disease and rates of mortality. Two well-established drivers of early-onset CRC in the general population are alterations in the WNT and TGF-Beta signaling pathways; however, the specific roles of these pathways in Hispanics/Latinos are poorly understood.

Methods: Here, we assessed CRC mutations in the WNT and TGF-Beta pathways by conducting a bioinformatics analysis using cBioPortal. Cases of CRC were stratified both by age and ethnicity: (1) early-onset was defined as <50 years vs. late-onset as ≥50 years; (2) we compared early-onset in Hispanics/Latinos to early-onset in NHWs.

Results: No significant differences were evident when we compared early-onset and late-onset CRC cases within the Hispanic/Latino cohort. These results are consistent with findings from large cohorts that do not specify ethnicity. However, we found significant differences when we compared early-onset CRC in Hispanic/Latino patients to early-onset CRC in NHW patients: specifically, alterations in the gene bone morphogenetic protein-7 (BMP7) were more frequent in early-onset CRC for the Hispanic/Latino patients. In addition to these findings, we observed that both NHW patients and Hispanic/Latino patients with early-onset disease had better clinical outcomes when there was evidence of WNT pathway alterations. Conversely, the absence of TGF-Beta pathway alterations was uniquely associated with improved outcomes exclusively in early-onset Hispanic/Latino patients.

Conclusions: In toto, these findings underscore how the WNT and TGF-Beta pathways may act differently in different ethnic groups with early-onset CRC. These findings may set a stage for developing new therapies tailored for reducing cancer health disparities.

Keywords: Hispanic/Latino populations; TGF-beta pathway; WNT pathway; early-onset colorectal cancer; ethnic disparities; genetic mutations; precision medicine.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Illustration of the WNT signaling pathway on the left and the TGF-beta signaling pathway on the right.
Figure 2
Figure 2
Overall survival curves of early-onset Hispanic/Latino patients stratified by the presence or absence of WNT (left) and TGF-β (right) pathway alterations.
See this image and copyright information in PMC

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