Article Impact Level: HIGH Data Quality: STRONG Summary of JCO Global Oncology, 11, e2400512. https://doi.org/10.1200/GO-24-00512 Dr. Ana Carolina de Carvalho et al.
Points
- Researchers conducted an extensive case-control study in Brazil to validate 45 known genetic variants and explore how ancestry influences the risk of developing non-hereditary colorectal cancer.
- The analysis confirmed that two genetic variants (rs10795668 and rs6066825) increase the risk of colorectal cancer, while two others (rs4939827 and rs6983267) offer a significant protective effect against the disease.
- A novel finding demonstrated that individuals with lower proportions of African and Asian genetic ancestry were more susceptible to developing colorectal cancer, suggesting a protective effect from these ancestries.
- With nearly 2,000 participants from across the country, this is one of the largest and most ethnically diverse genetic studies on colorectal cancer ever conducted in Brazil.
- Future research aims to integrate these genetic markers with lifestyle factors to develop personalized screening strategies and create a specific risk score tailored to Brazil’s unique admixed population.
Summary
An extensive case-control study in Brazil aimed to replicate the association of 45 known single-nucleotide polymorphisms (SNPs) with colorectal cancer (CRC) risk and assess the influence of genetic ancestry. The study initially included 990 cases of CRC and 1,027 controls, with a final matched cohort of 906 cases and 906 controls analyzed. Genotyping was successful for 35 SNPs, and genetic ancestry was assessed using 46 ancestry informative markers. The results validated four SNPs as significant independent modulators of CRC risk in this admixed population.
Multivariate analysis confirmed that two SNPs were associated with an increased risk of CRC: rs10795668 (LOC10537640), with an odds ratio (OR) of 1.98 (P = .003), and rs6066825 (PREX1), with an OR of 1.50 (P = .008). Conversely, two SNPs demonstrated a significant protective effect against CRC development: rs4939827 (SMAD7), with an OR of 0.61 (P = .001), and rs6983267 (CCAT2), with an OR of 0.65 (P = .013). These associations remained significant after adjusting for clinical and epidemiological factors.
The study also revealed a novel link between genetic ancestry and CRC susceptibility. Individuals in the lowest tercile for Asian ancestry had an increased risk (OR, 1.48; P = .001), as did those in the lowest tercile for African ancestry (OR, 1.22; P = .025). These findings suggest that components inherited from these ancestral populations may confer a protective effect. The study highlights the importance of validating genetic markers in diverse, admixed populations and lays the groundwork for developing personalized risk assessment and screening strategies in Brazil.
Link to the article: https://ascopubs.org/doi/10.1200/GO-24-00512
References De Carvalho, A. C., Laus, A. C., Lopes Junior, H. R., Porto, J., Sant’Anna Silva, D., Ribeiro, A. G., Datorre, J. G., Tavares, R. M., Sousa Carlos, A. B., Furquim, T., Uno, M., Chammas, R., Villela, P., Dos Reis, M. B., De Medeiros Matsushita, M., Oliveira, M. A., Hirai, W. Y., Guimarães, D. P., Santos, F. A., & Reis, R. M. (2025). Association of genetic ancestry and colorectal cancer risk in a large brazilian cohort: Replication of single-nucleotide polymorphisms identified by genome-wide association studies. JCO Global Oncology, 11, e2400512. https://doi.org/10.1200/GO-24-00512
