评估饮食摄入和多基因风险评分与结直肠癌风险的关联：来自英国生物银行的证据。

Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank.

机构信息

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Korea.

出版信息

BMC Cancer. 2023 Oct 18;23(1):993. doi: 10.1186/s12885-023-11482-1.

DOI:10.1186/s12885-023-11482-1

PMID:37853340

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10583398/

Abstract

BACKGROUND

This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk.

METHODS

We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term.

RESULTS

During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05-1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18-1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HR = 2.12, 95% CI = 1.97-2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08-1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00-1.19 for low vs. high WCRF dietary scores).

CONCLUSION

Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

摘要

背景

本研究旨在探索饮食摄入与遗传因素对结直肠癌（CRC）发病风险的潜在相互作用，以及在遗传风险较高的个体中，遵循健康饮食习惯是否能降低 CRC 风险。

方法

我们分析了 UK Biobank 中 374004 名无任何癌症的参与者的前瞻性队列数据。根据世界癌症研究基金会（WCRF）的三项饮食建议和使用逆方差（IV）法对 11 种食物对 CRC 风险的总体影响，创建了饮食评分。使用多基因风险评分（PRS）评估遗传风险，该评分捕捉总体 CRC 风险。使用 Cox 比例风险模型计算关联的危险比（HR）和 95%置信区间（CI）。通过似然比检验来检验饮食因素与 PRS 之间的相互作用，以比较包含和不包含交互项的模型。

结果

在中位随访 12.4 年期间，新诊断出 4686 例 CRC 病例。低依从 WCRF 建议（HR=1.12，95%CI=1.05-1.19）和高 IV 加权饮食评分（HR=1.27，95%CI=1.18-1.37）均与 CRC 风险相关。98 个遗传变异的 PRS 与 CRC 风险增加相关（HR=2.12，95%CI=1.97-2.29）。具有不良饮食习惯和高 PRS 的参与者发生 CRC 的风险增加了两倍以上；然而，交互作用并不显著。遵循整体健康饮食可能会降低遗传风险较高者的 CRC 风险（高 IV 加权饮食评分者的 HR=1.21，95%CI=1.08-1.35，而低 IV 加权饮食评分者的 HR=1.09，95%CI=1.00-1.19），而对 WCRF 饮食建议的依从性仅显示出边缘效应（低 WCRF 饮食评分者的 HR=1.09，95%CI=1.00-1.19）。