Xi Zhihui, Feng Huolun, Chen Kunling, Guo Xin, Zhu Dandan, Zheng Jiabin, Li Yong
School of Medicine, South China University of Technology, Guangzhou, Guangdong, PR China; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, PR China.
School of Medicine, South China University of Technology, Guangzhou, Guangdong, PR China; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, PR China.
Transl Oncol. 2025 Feb;52:102242. doi: 10.1016/j.tranon.2024.102242. Epub 2024 Dec 15.
Gastric cancer is often diagnosed at an advanced stage and at order age, identification of high-risk population is needed for detection of early-stage gastric cancer.
To examine whether clonal hematopoiesis of indeterminate potential (CHIP) is a risk factor of gastric cancer.
This cohort study used data from the UK Biobank collected from baseline (2006-2010) to the end of follow-up in March 2024.
Data on age, sex, race, alcohol consumption, smoking status and type 2 diabetes were collected at baseline interview. Previous and diagnosed cancer or diseases were collected from self-reported and in-hospital records.
Participants with no previous cancer or hematologic disorders were selected. Participants with gastric cancer cases were aged 60.7 (S.D. 6.62), 71.8 % male; controls were aged 56.1 (S.D. 8.11), 47.4 % male.
Whole-exome sequencing was performed on blood samples collected at baseline. A CHIP status was identified based on the mutations on 43 CHIP-related genes.
Odds ratio (OR) of CHIP with gastric cancer risk was estimated using multivariable logistic regression models. Participants were grouped based on age and CHIP status to examine if there are differences in the cumulative incidence of gastric cancer.
Among 402,253 participants, 1,070 incident gastric cancer cases were identified (mean age, 60.7 ± 6.62 years). The prevalence of CHIP at baseline was associated with an increased risk of gastric cancer (cases: 6.54 % vs. controls 5.14 %; OR without adjustment, 1.29; 95 % CI, 1.004 to 1.63). The stratified OR (95 % CI) of individuals aged ≥ 57 was 1.33 (1.02 to 1.72) for overall CHIP, whereas the OR for younger individuals was 0.79 (0.37 to 1.44). CHIP involving DNMT3A (OR, 1.81; 95 % CI, 1.05 to 2.88; P = 0.0193) and ASXL1 (OR, 2.43; 95 % CI, 0.95 to 4.99; P = 0.032) was associated with an increased risk of gastric cancer. These positive associations remained significantly in sensitivity analyses adjusted by known risk factors. Compared to younger individuals and non-CHIP carriers, older participants with CHIP exhibited a significantly higher cumulative incidence of gastric cancer (P < 0.0001).
CHIP is associated with gastric cancer in the elderly and contributes to the positive association between DNM3A and ASXL1 mutations and risk of gastric cancer.
胃癌通常在晚期和老年时被诊断出来，因此需要识别高危人群以检测早期胃癌。
研究不确定潜能克隆造血（CHIP）是否为胃癌的危险因素。
这项队列研究使用了英国生物银行从基线（2006 - 2010年）到2024年3月随访结束时收集的数据。
在基线访谈时收集年龄、性别、种族、饮酒量、吸烟状况和2型糖尿病的数据。既往和确诊的癌症或疾病从自我报告和住院记录中收集。
选择无既往癌症或血液系统疾病的参与者。胃癌病例参与者的年龄为60.7岁（标准差6.62），男性占71.8%；对照组年龄为56.1岁（标准差8.11），男性占47.4%。
对基线时采集的血样进行全外显子测序。根据43个与CHIP相关基因的突变确定CHIP状态。
使用多变量逻辑回归模型估计CHIP与胃癌风险的比值比（OR）。根据年龄和CHIP状态对参与者进行分组，以检查胃癌累积发病率是否存在差异。
在402,253名参与者中，确定了1,070例新发胃癌病例（平均年龄，60.7±6.62岁）。基线时CHIP的患病率与胃癌风险增加相关（病例组：6.54% vs.对照组5.14%；未调整的OR，1.29；95%CI，1.004至1.63）。年龄≥57岁个体的总体CHIP分层OR（95%CI）为1.33（1.02至1.72），而较年轻个体的OR为0.79（0.37至1.44）。涉及DNMT3A（OR，1.81；95%CI，1.05至2.88；P = 0.0193）和ASXL1（OR，2.43；95%CI，0.95至4.99；P = 0.032）的CHIP与胃癌风险增加相关。在通过已知危险因素调整的敏感性分析中，这些阳性关联仍然显著。与较年轻个体和非CHIP携带者相比，患有CHIP的老年参与者的胃癌累积发病率显著更高（P < 0.0001）。
CHIP与老年人的胃癌相关，并导致DNM3A和ASXL1突变与胃癌风险之间的正相关。
