Department of Epidemiology and Biostatistics, School of Public Health; Department of Gastrointestinal Oncology, Zhongnan Hospital, Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Int J Cancer. 2023 Aug 1;153(3):499-511. doi: 10.1002/ijc.34544. Epub 2023 Apr 23.
Previous investigations mainly focused on the associations of dietary fatty acids with colorectal cancer (CRC) risk, which ignored gene-environment interaction and mechanisms interpretation. We conducted a case-control study (751 cases and 3058 controls) and a prospective cohort study (125 021 participants) to explore the associations between dietary fatty acids, genetic risks, and CRC. Results showed that high intake of saturated fatty acid (SFA) was associated with a higher risk of CRC than low SFA intake (HR =1.22, 95% CI:1.02-1.46). Participants at high genetic risk had a greater risk of CRC with the HR of 2.48 (2.11-2.91) than those at low genetic risk. A multiplicative interaction of genetic risk and SFA intake with incident CRC risk was found (P = 7.59 × 10 ), demonstrating that participants with high genetic risk and high SFA intake had a 3.75-fold greater risk of CRC than those with low genetic risk and low SFA intake. Furthermore, incorporating PRS and SFA into traditional clinical risk factors improved the discriminatory accuracy for CRC risk stratification (AUC from 0.706 to 0.731). Multi-omics data showed that exposure to SFA-rich high-fat dietary (HFD) can responsively induce epigenome reprogramming of some oncogenes and pathological activation of fatty acid metabolism pathway, which may contribute to CRC development through changes in gut microbiomes, metabolites, and tumor-infiltrating immune cells. These findings suggest that individuals with high genetic risk of CRC may benefit from reducing SFA intake. The incorporation of SFA intake and PRS into traditional clinical risk factors will help improve high-risk sub-populations in individualized CRC prevention.
先前的研究主要集中在饮食脂肪酸与结直肠癌（CRC）风险之间的关联上，这些研究忽略了基因-环境相互作用和机制解释。我们进行了一项病例对照研究（751 例病例和 3058 例对照）和一项前瞻性队列研究（125021 名参与者），以探讨饮食脂肪酸、遗传风险与 CRC 之间的关系。结果表明，与低 SFA 摄入相比，高 SFA 摄入与 CRC 风险升高相关（HR=1.22，95%CI：1.02-1.46）。遗传风险高的参与者患 CRC 的风险更高，HR 为 2.48（2.11-2.91），而遗传风险低的参与者则更低。遗传风险和 SFA 摄入与 CRC 发病风险之间存在乘法交互作用（P=7.59×10-4），表明遗传风险高和 SFA 摄入高的参与者患 CRC 的风险比遗传风险低和 SFA 摄入低的参与者高 3.75 倍。此外，将 PRS 和 SFA 纳入传统临床危险因素可提高 CRC 风险分层的区分准确性（AUC 从 0.706 提高到 0.731）。多组学数据表明，暴露于富含 SFA 的高脂肪饮食（HFD）可响应性地诱导一些致癌基因的表观基因组重编程和脂肪酸代谢途径的病理性激活，这可能通过改变肠道微生物组、代谢物和肿瘤浸润免疫细胞来促进 CRC 的发展。这些发现表明，CRC 遗传风险高的个体可能受益于减少 SFA 摄入。将 SFA 摄入和 PRS 纳入传统临床危险因素将有助于改善个体化 CRC 预防中的高危亚人群。
