Colorectal Cancer Risk Loci: Prognostic Factors for Clinical Outcomes? A Systematic Review and Meta-Analysis

IF 1.5 Q4 ONCOLOGY

Cancer reports Pub Date : 2025-05-19 DOI:10.1002/cnr2.70230

Chengmi Wu, Jingyi Zhou, Qian Wu, Shu Xu, Jie Jiang, Sha Li, Xuechen Chen

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Abstract

Background

Several single nucleotide polymorphisms (SNPs) identified through genome-wide association studies (GWASs) on colorectal cancer (CRC) incidence are also shown as promising predictors of clinical outcomes in CRC patients. These genetic variants might help inform precision prognostic strategies by predicting disease progression, treatment response, and overall survival, thereby guiding more personalized treatment plans. However, conflicting evidence exists regarding their clinical relevance.

Aim

A systematic review and meta-analysis was performed to assess the potential of GWAS-identified SNPs in predicting CRC outcomes.

Methods and Results

We conducted a comprehensive search of PubMed, Web of Science, Embase, and Cochrane databases up to 18 October 2024 for prospective studies that investigated the associations of CRC-related SNPs and polygenic risk scores (PRSs) built based on multiple SNPs with clinical outcomes. Quality of the included studies was assessed using the Newcastle–Ottawa Scale, and the heterogeneity was assessed by I² index and Cochran's Q test. The final analysis included 22 studies with overall high quality and heterogeneity in several aspects (e.g., genetic models, ethnic background, and genetic signatures of CRC types). Among over 100 CRC risk-related loci, 12 SNPs were statistically associated with CRC clinical outcomes (mainly survival outcomes), which were replicated in multiple studies. Notably, rs9929218 and rs6983267, located in genes involved in processes of tumorigenesis, were linked to poor survival with hazard ratios (95% CIs) of 1.26 (1.12–1.42) under a recessive model and 1.33 (1.10–1.61) under an additive model, respectively, in the stratified analysis by genetic models. Besides, PRSs built based on survival-related SNPs were moderately associated with overall survival in CRC patients with hazard ratios exceeding 2.6 for each one-point increase in PRS.

Conclusions

Individual genetic variants and PRSs are predictive of CRC survival, and might serve as potential factors for risk stratification, which could help develop personalized treatment and surveillance strategies for CRC patients. However, the potential for false positives and the significant heterogeneity among studies that cannot be fully addressed in the current analysis due to limited data require a cautious interpretation of these findings. Large-scale studies are warranted to further explore and validate GWAS-identified SNPs for promising prognostic biomarkers in CRC patients while accounting for factors such as ethnic differences and tumor subtypes.

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结直肠癌风险位点：影响临床结果的预后因素？系统回顾和荟萃分析

背景：通过全基因组关联研究（GWASs）发现的几种与结直肠癌（CRC）发病率相关的单核苷酸多态性（snp）也被证明是结直肠癌患者临床预后的有希望的预测因子。这些基因变异可能有助于通过预测疾病进展、治疗反应和总体生存来提供精确的预后策略，从而指导更个性化的治疗计划。然而，关于它们的临床相关性，存在相互矛盾的证据。目的进行系统回顾和荟萃分析，以评估gwas鉴定的snp在预测结直肠癌结局方面的潜力。方法与结果我们对PubMed、Web of Science、Embase和Cochrane数据库进行了全面检索，检索了截至2024年10月18日的前瞻性研究，这些研究调查了crc相关snp和基于多个snp构建的多基因风险评分（PRSs）与临床结果的关系。采用Newcastle-Ottawa量表评估纳入研究的质量，采用I2指数和Cochran’s Q检验评估异质性。最终的分析包括22项研究，在几个方面（如遗传模型、种族背景和CRC类型的遗传特征）具有总体高质量和异质性。在100多个CRC风险相关基因座中，有12个snp与CRC临床结局（主要是生存结局）有统计学相关性，这在多个研究中得到了重复。值得注意的是，在遗传模型分层分析中，rs9929218和rs6983267位于参与肿瘤发生过程的基因中，与低生存率相关，在隐性模型下的风险比（95% ci）为1.26(1.12-1.42)，在加性模型下的风险比为1.33（1.10-1.61）。此外，基于生存相关snp构建的PRS与CRC患者的总生存率存在中度相关性，PRS每增加1个点的风险比超过2.6。结论个体遗传变异和PRSs可预测结直肠癌患者的生存，并可能作为风险分层的潜在因素，有助于制定针对结直肠癌患者的个性化治疗和监测策略。然而，由于数据有限，在目前的分析中不能完全解决假阳性的可能性和研究之间的显著异质性，因此需要谨慎解释这些发现。在考虑种族差异和肿瘤亚型等因素的同时，有必要进行大规模研究，以进一步探索和验证gwas鉴定的snp在结直肠癌患者中有希望的预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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