Saturated fatty acid intake, genetic risk and colorectal cancer incidence: A large-scale prospective cohort study
Linyun Fan
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
Search for more papers by this authorYimin Cai
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
Search for more papers by this authorHaoxue Wang
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
Search for more papers by this authorHeng Zhang
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
Search for more papers by this authorCan Chen
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorMing Zhang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZequn Lu
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorYanmin Li
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorFuwei Zhang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorCaibo Ning
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorWenzhuo Wang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorYizhuo Liu
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
Search for more papers by this authorHanting Li
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
Search for more papers by this authorGaoyuan Li
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
Search for more papers by this authorJingyi Peng
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
Search for more papers by this authorKexin Hu
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
Search for more papers by this authorBin Li
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
Search for more papers by this authorChaoqun Huang
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
Search for more papers by this authorXiaojun Yang
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
Search for more papers by this authorYongchang Wei
Department of Gastrointestinal Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
Search for more papers by this authorYing Zhu
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
Search for more papers by this authorCorresponding Author
Meng Jin
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Correspondence
Meng Jin, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Email: [email protected]
Xiaoping Miao and Jianbo Tian, Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xiaoping Miao
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
Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
Research Center of Public Health, Renmin hospital of Wuhan University, Wuhan University, Wuhan, China
Correspondence
Meng Jin, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Email: [email protected]
Xiaoping Miao and Jianbo Tian, Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Jianbo Tian
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
Research Center of Public Health, Renmin hospital of Wuhan University, Wuhan University, Wuhan, China
Correspondence
Meng Jin, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Email: [email protected]
Xiaoping Miao and Jianbo Tian, Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.
Email: [email protected] and [email protected]
Search for more papers by this authorLinyun Fan
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
Search for more papers by this authorYimin Cai
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
Search for more papers by this authorHaoxue Wang
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
Search for more papers by this authorHeng Zhang
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
Search for more papers by this authorCan Chen
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorMing Zhang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZequn Lu
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorYanmin Li
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorFuwei Zhang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorCaibo Ning
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorWenzhuo Wang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorYizhuo Liu
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
Search for more papers by this authorHanting Li
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
Search for more papers by this authorGaoyuan Li
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
Search for more papers by this authorJingyi Peng
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
Search for more papers by this authorKexin Hu
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
Search for more papers by this authorBin Li
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
Search for more papers by this authorChaoqun Huang
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
Search for more papers by this authorXiaojun Yang
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
Search for more papers by this authorYongchang Wei
Department of Gastrointestinal Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
Search for more papers by this authorYing Zhu
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
Search for more papers by this authorCorresponding Author
Meng Jin
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Correspondence
Meng Jin, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Email: [email protected]
Xiaoping Miao and Jianbo Tian, Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xiaoping Miao
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
Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
Research Center of Public Health, Renmin hospital of Wuhan University, Wuhan University, Wuhan, China
Correspondence
Meng Jin, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Email: [email protected]
Xiaoping Miao and Jianbo Tian, Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Jianbo Tian
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
Research Center of Public Health, Renmin hospital of Wuhan University, Wuhan University, Wuhan, China
Correspondence
Meng Jin, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Email: [email protected]
Xiaoping Miao and Jianbo Tian, Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.
Email: [email protected] and [email protected]
Search for more papers by this authorLinyun Fan, Yimin Cai, Haoxue Wang and Heng Zhang have contributed equally to this study.
Abstract
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 (PInteraction = 7.59 × 10−20), 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.
Graphical Abstract
What's new?
A complex interplay between environmental and genetic risk factors is thought to be involved in colorectal cancer. However, previous studies mainly focused on the associations of dietary fatty acids with colorectal cancer risk. Here, the authors report synergistic effects between saturated fatty acid intake and polygenic risk score on incident colorectal cancer risk. The findings highlight the importance of low saturated fatty acid intake, particularly in subjects at high genetic risk of colorectal cancer. Furthermore, the authors present a predictive model combining saturated fatty acid intake and polygenic risk score, which may provide valuable risk stratification guidance for diet recommendations.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data from UK Biobank (www.ukbiobank.ac.uk/register-apply) are available to all researchers upon making an application. This research has been conducted using the UKB Resource under the Application number 94939. All source code is publicly available on GitHub (https://github.com/zeroflyer/SFA-intake). Other data that support the findings of this study are available from the corresponding author upon request.
The North West Multi-Centre Research Ethics Committee approved the collection and use of UK Biobank data. All participants provided written informed consent. Institutional review board approval was waived for this analysis because of the publicly available and de-identified data. The study was conducted with the approval of the Institutional Review Board of Wuhan university (ID:2022042).
Supporting Information
| Filename | Description |
|---|---|
| ijc34544-sup-0001-Supinfo.pdfPDF document, 713.9 KB | DATA S1. Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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