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

IF 3 Q2 ONCOLOGY

JCO Global Oncology Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI:10.1200/GO-24-00512

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

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Abstract

Purpose: Genome-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.

Methods: A 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.

Results: Genotyping 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.

Conclusion: Our 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.

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在一个大型巴西队列中，遗传祖先与结直肠癌风险的关联：由全基因组关联研究确定的单核苷酸多态性的复制。

目的：全基因组关联研究已经确定了欧洲和亚洲人群中与结直肠癌（CRC）风险相关的几种单核苷酸多态性（snp），但对混合人群（如巴西人）的研究仍然很少。我们的目的是在一个大型巴西队列中复制45个与结直肠癌风险相关的snp，并探索它们与遗传祖先的相关性。方法：一项病例-对照研究包括巴西的990例CRC病例和1027例对照。我们使用snp型分析对45个snp进行基因分型，并使用46个祖先信息标记对祖先进行评估。将病例和对照组按性别和年龄进行匹配后，对906例病例和906例对照组进行分析。结果：35个snp基因分型成功，其中9个与结直肠癌相关。多因素分析证实两个snp与CRC风险增加相关，rs10795668(优势比[OR]， 1.98；P = 0.003)和rs6066825 (OR, 1.50；P = 0.008)，两个snp具有保护作用：rs4939827 (OR, 0.61；P = .001)和rs6983267 (OR, 0.65；P = .013)。低亚洲(最低不育，OR, 1.48；P = .001)和低非洲(最低不育，OR, 1.22；P = 0.025)的血统增加了结直肠癌的风险。结论：我们的研究结果证实了rs10795668 （LOC10537640）、rs4939827 （SMAD7）、rs6066825 （PREX1）和rs6983267 （CCAT2）在巴西人CRC风险中的多态性，并提示较低的亚洲和非洲血统可能影响CRC易感性。

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