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基于上海郊区成人队列和生物样本库的豆制品摄入量与肺癌风险的前瞻性队列研究

[A Prospective Cohort Study on Soy Product Intake and the Risk of Lung Cancer 
Based on Shanghai Suburban Adult Cohort and Biobank].

作者信息

Ding Shiyun, Wu Wenhui, Mao Jianing, Li Jingrao, Zheng Ji, Yao Ye, Zhao Genming, Wu Yiling, Zhang Ruoxin

机构信息

Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, 
Fudan University, Shanghai 200030, China.

Yiwu Research Institute, Fudan University, Yiwu 322000, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2025 Apr 20;28(4):291-303. doi: 10.3779/j.issn.1009-3419.2025.106.09.

Abstract

BACKGROUND

Lung cancer is one of the malignant cancers with the highest incidence rate, and it is important to identify the factors contributing to lung cancer carcinogenesis for prevention. Lifestyle and genetic factors play important roles in cancer development, however the impact of dietary factors, such as soy product intake, on lung cancer risk remains inadequately understood. This study aims to explore the associations between soy product intake, genetic risk, and lung cancer incidence, and validate the consistent effects of soy product intake in European populations, thereby providing new insights for lung cancer prevention.

METHODS

Utilizing the Shanghai Suburban Adult Cohort and Biobank (SSACB) (n=66,311), Cox proportional hazards model was adopted to assess the association between soy product intake and lung cancer incidents, followed by subgroup analyses stratified by gender, smoking status, and pathological types of lung cancer. The UK Biobank (UKB) was used for validation of the effect of soy product intake on lung cancer. To investigate the association between genetic factors and lung cancer, in addition to previously reported loci, we incorporated newly identified loci from two independent studies in Southeast China: a nested case-control population from the SSACB cohort (433 cases/650 controls) and a case-control study from the Shanghai Cancer Center-Taizhou cohort (1359 cases/1359 controls). Meta-analysis and Linkage disequilibrium clumping (LD clumping) of the association results identified 23 loci for polygenic risk score (PRS) construction. Subsequently, conditional Logistic regression model was used to assess the association between genetic risk and lung cancer.

RESULTS

In SSACB cohort, after adjusting for age, gender, smoking, chronic bronchitis, body mass index (BMI), vegetable intake and red meat intake, sufficient soy product intake was significantly associated with a reduced risk of lung cancer [hazard ratio (HR)=0.60, 95%CI: 0.47-0.77, Padj=6.69E-05], an effect that was consistent in males and females, smokers and non-smokers. In UKB, although the association did not reach statistical significance, a protective trend against lung cancer was also observed (HR=0.76, 95%CI: 0.55-1.06, Padj=0.10). In the nested case-control population within SSACB, a PRS score generated in the Chinese population was significantly correlated with lung cancer risk. After adjustment of age, gender, smoking, chronic bronchitis, and soy product intake, the high-PRS group had a 1.88 times higher risk of lung cancer compared to the low-PRS group (Padj=1.84E-03).

CONCLUSIONS

The prospective cohort study found that adequate intake of soy products was significantly associated with a reduced risk of lung cancer, while a high PRS is a risk factor for lung cancer development. Integrating soy product intake and PRS into traditional epidemiological risk factor prediction will guide personalized lung cancer prevention and high-risk population stratification.

摘要

背景

肺癌是发病率最高的恶性肿瘤之一,识别肺癌发生的相关因素对预防至关重要。生活方式和遗传因素在癌症发展中起重要作用,然而,饮食因素(如豆制品摄入)对肺癌风险的影响仍未得到充分了解。本研究旨在探讨豆制品摄入、遗传风险与肺癌发病率之间的关联,并验证欧洲人群中豆制品摄入的一致效应,从而为肺癌预防提供新的见解。

方法

利用上海郊区成人队列和生物样本库(SSACB)(n = 66311),采用Cox比例风险模型评估豆制品摄入与肺癌发病之间的关联,随后按性别、吸烟状况和肺癌病理类型进行亚组分析。英国生物样本库(UKB)用于验证豆制品摄入对肺癌的影响。为研究遗传因素与肺癌之间的关联,除先前报道的基因座外,我们纳入了来自中国东南部两项独立研究新发现的基因座:SSACB队列中的巢式病例对照人群(433例病例/650例对照)和上海癌症中心 - 泰州队列的病例对照研究(1359例病例/1359例对照)。对关联结果进行荟萃分析和连锁不平衡聚类(LD聚类),确定了23个用于构建多基因风险评分(PRS)的基因座。随后,使用条件逻辑回归模型评估遗传风险与肺癌之间的关联。

结果

在SSACB队列中,调整年龄、性别、吸烟、慢性支气管炎、体重指数(BMI)、蔬菜摄入和红肉摄入后,充足的豆制品摄入与肺癌风险降低显著相关[风险比(HR)= 0.60,95%CI:0.47 - 0.77,Padj = 6.69E - 05],这种效应在男性和女性、吸烟者和非吸烟者中均一致。在UKB中,尽管该关联未达到统计学显著性,但也观察到对肺癌的保护趋势(HR = 0.76,95%CI:0.55 - 1.06,Padj = 0.10)。在SSACB队列中的巢式病例对照人群中,中国人群中生成的PRS评分与肺癌风险显著相关。调整年龄、性别、吸烟、慢性支气管炎和豆制品摄入后,高PRS组患肺癌的风险是低PRS组的1.88倍(Padj = 1.84E - 03)。

结论

前瞻性队列研究发现,适量摄入豆制品与肺癌风险降低显著相关,而高PRS是肺癌发生的危险因素。将豆制品摄入和PRS纳入传统的流行病学危险因素预测将指导个性化的肺癌预防和高危人群分层。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea4/12096097/287b009b6734/img_1.jpg

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