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

## TL;DR

This study finds that eating more soy products may lower lung cancer risk and identifies genetic factors that increase risk.

## Contribution

The study is the first to investigate the combined effect of soy intake and genetic risk on lung cancer in Chinese and European populations.

## Key findings

- Higher soy product intake was associated with a 40% lower lung cancer risk in Shanghai cohort.
- A polygenic risk score based on 23 genetic variants identified high-risk individuals with 88% increased lung cancer risk.
- The protective effect of soy was consistent across genders and smoking status in the Chinese cohort.

## Abstract

肺癌是全世界发病率最高的恶性肿瘤之一，探索肺癌发病的影响因素对其防治具有重要意义。尽管生活习惯和遗传因素已被证实与肺癌的发生密切相关，但饮食因素，如豆制品摄入对肺癌发病风险的影响仍不完全明确。本研究旨在探讨豆制品摄入、遗传风险与肺癌发病风险之间的关联，验证豆制品摄入在欧洲人群中的效应一致性，为肺癌防治提供新的思路。

本研究首先基于上海郊区自然人群队列（Shanghai Suburban Adult Cohort and Biobank, SSACB）（n=66,311）使用Cox比例风险回归模型分析豆制品摄入与肺癌发病风险之间的关联，并根据性别、吸烟及肺癌病理类型对人群进行分层分析。采用英国生物银行（UK Biobank, UKB）人群验证豆制品对于肺癌发病的影响。在探究遗传因素与肺癌发病的关联中，在整合既往研究报道的中国人群遗传变异的基础上新增了东南地区两大独立人群的新发现位点进行补充，包括SSACB（433例病例/650例对照）及肿瘤医院-泰州队列（1359例病例/1359例对照）。通过meta分析及连锁不平衡聚类分析（linkage disequilibrium clumping, LD clumping）后，最终筛选出23个显著位点，用于构建多基因风险评分（polygenic risk score, PRS）模型。随后，利用条件Logistic回归模型评估PRS对肺癌发病风险的影响。

在SSACB人群中，调整年龄、性别、吸烟、慢性支气管炎、身体质量指数（body mass index, BMI）、蔬菜及红肉摄入后发现，摄入足量豆制品与肺癌发病风险降低有显著关联[风险比（hazard ratio, HR）=0.60，95%CI: 0.47-0.77，Padj=6.69E-05]，且该效应在男性、女性、吸烟和非吸烟人群中均保持一致。在UKB人群中豆制品与肺癌发病的关系虽然没有统计学差异，但也呈现出对肺癌的保护趋势（HR=0.76, 95% CI: 0.55-1.06, Padj=0.10）。在SSACB的巢式病例对照人群中，基于中国人群构建的PRS评分与肺癌发病显著相关，调整年龄、性别、吸烟、慢性支气管炎及豆制品摄入后，与低风险人群相比，高PRS评分人群的发病风险是低评分人群的1.88倍（Padj=1.84E-03）。

通过前瞻性队列研究发现，摄入足量豆制品可显著降低肺癌发病风险，而高PRS是肺癌发病的重要危险因素。将豆制品摄入量和PRS作为肺癌发病的影响因素进行综合评估，可为肺癌高危人群的个体化分层和精准预防提供一定指导作用。

Baseline demographic characteristics of SSACB

Baseline demographic characteristics of UKB

Association between dietary factors and lung cancer in SSACB

VIF matrix of dietary information in SSACB

Association between variables and lung cancer risk in UKB

Association of the 23 SNPs used for Chinese population PRS in the nested case-control population in SSACB

Association between low, intermediate, and high genetic risk and lung cancer incidence