潜在克隆性造血作为结直肠癌风险的预测指标：来自英国生物银行队列的见解

Clonal Hematopoiesis of Indeterminate Potential as a Predictor of Colorectal Cancer Risk: Insights from the UK Biobank Cohort.

作者信息

Liu Yongfeng, Xi Zhihui, Zhou Jianlong, Ling Fa, Zhang Yucheng, Xie Huajie, Zheng Jiabin, Xia Baijin, Feng Huolun, Li Yong

机构信息

Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

School of Medicine, South China University of Technology, Guangzhou, China.

出版信息

Cancer Epidemiol Biomarkers Prev. 2025 Mar 3;34(3):405-411. doi: 10.1158/1055-9965.EPI-24-1342.

DOI:10.1158/1055-9965.EPI-24-1342

PMID:39804050

Abstract

BACKGROUND

Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with the occurrence of solid tumors, but its relationship with colorectal cancer still needs to be studied.

METHODS

We conducted a prospective matched case-control study using data from the UK Biobank, including 5,310 incident colorectal cancer cases and 26,550 controls matched for age, sex, and body mass index.

RESULTS

Analysis of the UK Biobank data revealed that the presence of CHIP was associated with an increased risk of colorectal cancer. The odds ratio (OR) for colorectal cancer in the presence of CHIP was 1.20 (P = 0.006). This association remained significant even after excluding participants with a family history of bowel cancer (multivariate OR, 1.19; P = 0.007). Subgroup analyses demonstrated that CHIP independently increased the risk of colorectal cancer in females (multivariate OR, 1.25; P = 0.018) and in individuals older than 60 years (multivariate OR, 1.17; P = 0.046). Gene-specific analyses revealed that mutations in TET2 and ATM were particularly significant in relation to colorectal cancer risk, with an OR of 1.62 (P = 0.002) for TET2 and 2.98 (P < 0.001) for ATM.

CONCLUSIONS

Our findings indicate that CHIP is associated with an increased risk of colorectal cancer, particularly in individuals more than 60 years of age or in females.

IMPACT

Screening for CHIP in the population may improve the early detection and diagnosis rates of colorectal cancer.

摘要

背景

已证明不确定潜能的克隆性造血（CHIP）与实体瘤的发生有关，但其与结直肠癌的关系仍有待研究。

方法

我们使用英国生物银行的数据进行了一项前瞻性匹配病例对照研究，包括5310例新发结直肠癌病例和26550例年龄、性别和体重指数相匹配的对照。

结果

对英国生物银行数据的分析显示，CHIP的存在与结直肠癌风险增加有关。存在CHIP时患结直肠癌的优势比（OR）为1.20（P = 0.006）。即使排除有肠癌家族史的参与者后，这种关联仍然显著（多变量OR，1.19；P = 0.007）。亚组分析表明，CHIP独立增加女性（多变量OR，1.25；P = 0.018）和60岁以上个体（多变量OR，1.17；P = 0.046）患结直肠癌的风险。基因特异性分析显示，TET2和ATM的突变与结直肠癌风险特别相关，TET2的OR为1.62（P = 0.002），ATM的OR为2.98（P < 0.001）。