Association of Genetic Ancestry and Colorectal Cancer Risk in a Large Brazilian Cohort: Replication of Single-Nucleotide Polymorphisms Identified by Genome-Wide Association Studies

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de Carvalho, Ana Carolina ; Laus, Ana Carolina ; Lopes Junior, Howard Ribeiro ; Porto, Jun ; Sant'Anna Silva, Debora ; Ribeiro, Adeylson Guimaraes ; Datorre, Jose Guilherme ; Tavares, Rosielly Melo ; Sousa Carlos, Anne Beatriz ; Furquim, Tulio ; Uno, Miyuki ; Chammas, Roger ; Villela, Priscilla ; dos Reis, Mariana Bisarro ; de Medeiros Matsushita, Marcus ; Oliveira, Marco Antonio ; Hirai, Welinton Yoshio ; Guimaraes, Denise Peixoto ; Santos, Florinda Almeida ; Reis, Rui Manuel

• Document type: Journal article
• Source: JCO GLOBAL ONCOLOGY; v. 11, p. 25-pg., 2025-06-01.

Abstract

PURPOSEGenome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) linked to colorectal cancer (CRC) risk in European and Asian populations, but studies in admixed populations, like Brazilians, remain scarce. We aimed to replicate 45 SNPs associated with CRC risk and explore their correlation with genetic ancestry in a large Brazilian cohort.METHODSA case-control study included 990 CRC cases and 1,027 controls in Brazil. We genotyped 45 SNPs using SNPtype assays and assessed ancestry with 46 ancestry informative markers. After matching cases and controls by sex and age, 906 cases and 906 controls were analyzed.RESULTSGenotyping succeeded for 35 SNPs, and nine showed significant CRC associations. Multivariate analysis confirmed two SNPs linked to increased CRC risk, rs10795668 (odds ratio [OR], 1.98; P = .003) and rs6066825 (OR, 1.50; P = .008), and two SNPs with protective effects: rs4939827 (OR, 0.61; P = .001) and rs6983267 (OR, 0.65; P = .013). Low Asian (lowest tercile, OR, 1.48; P = .001) and low African (lowest tercile, OR, 1.22; P = .025) ancestry increased CRC risk.CONCLUSIONOur findings validated rs10795668 (LOC10537640), rs4939827 (SMAD7), rs6066825 (PREX1), and rs6983267 (CCAT2) polymorphisms in CRC risk among Brazilians and suggest that lower Asian and African ancestries might influence CRC susceptibility. (AU)

• FAPESP's process: 21/13861-0 - Fecal microbiome profile as an early detection biomarker in Colorectal Cancer in liquid biopsy
• Grantee: Mariana Bisarro dos Reis
• Support Opportunities: Scholarships in Brazil - Post-Doctoral