Dietary intake of branched-chain amino acids and survival after colorectal cancer diagnosis
Lu Long
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Search for more papers by this authorWanshui Yang
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, China
Search for more papers by this authorLi Liu
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorDeirdre K. Tobias
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorRyoko Katagiri
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Search for more papers by this authorKana Wu
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorLina Jin
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
Search for more papers by this authorFang-Fang Zhang
Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, USA
Search for more papers by this authorXiao Luo
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Department of Health Statistics, School of Public Health, China Medical University, Shenyang, Liaoning, China
Search for more papers by this authorXing Liu
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorShuji Ogino
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorAndrew T. Chan
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
Search for more papers by this authorJeffrey A. Meyerhardt
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorEdward Giovannucci
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorCorresponding Author
Xuehong Zhang
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Correspondence
Xuehong Zhang, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Room 453, Boston, MA 02115.
Email: [email protected]
Search for more papers by this authorLu Long
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Search for more papers by this authorWanshui Yang
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, China
Search for more papers by this authorLi Liu
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorDeirdre K. Tobias
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorRyoko Katagiri
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Search for more papers by this authorKana Wu
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorLina Jin
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
Search for more papers by this authorFang-Fang Zhang
Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, USA
Search for more papers by this authorXiao Luo
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Department of Health Statistics, School of Public Health, China Medical University, Shenyang, Liaoning, China
Search for more papers by this authorXing Liu
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorShuji Ogino
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorAndrew T. Chan
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
Search for more papers by this authorJeffrey A. Meyerhardt
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorEdward Giovannucci
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Search for more papers by this authorCorresponding Author
Xuehong Zhang
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Correspondence
Xuehong Zhang, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Room 453, Boston, MA 02115.
Email: [email protected]
Search for more papers by this authorFunding information: American Cancer Society Research Scholar Grant, Grant/Award Number: RSG NEC-130476; Dana-Farber Harvard Cancer Center (DF/HCC) GI SPORE Developmental Research Project Award, Grant/Award Number: P50CA127003; DF/HCC Cancer Center Support Grant, Grant/Award Number: 5P30CA006516-55; Harvard T.H. Chan School of Public Health; National Cancer Institute, Grant/Award Numbers: P01 CA055075, P01 CA087969, U01 CA167552, UM1 CA167552, UM1 CA186107; National Institutes of Health, Grant/Award Numbers: K07 CA188126, K24 DK098311, R01 CA137178, R01 CA151993, R01 CA248857, R21 CA238651, R35 CA197735
Abstract
Branched-chain amino acids (BCAAs), including leucine, isoleucine and valine, may potentially influence cancer progression by various mechanisms including its role in insulin resistance. However, the association of BCAAs with survival among patients with established colorectal cancer (CRC) remains unclear. We evaluated the associations between postdiagnostic BCAA intake with CRC-specific mortality and overall mortality among 1674 patients with nonmetastatic CRC in the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire. Multivariable hazard ratios (HRs) were calculated using Cox proportional-hazards regression model after adjustment for tumor characteristics and potential confounding factors. Comparing the highest with the lowest quartile intake of postdiagnostic total BCAA, the multivariable HRs were 1.18 (95% confidence interval [CI], 0.75-1.85, P for trend = .46 across quartiles) for CRC-specific mortality and 1.30 (95% CI, 1.01-1.69, P for trend = .04) for all-cause mortality. The multivariable HRs (the highest vs the lowest quartile) for all-cause mortality were 1.33 (95% CI, 1.03-1.73, Ptrend = .02) for valine, 1.28 (95% CI, 0.99-1.66, P for trend = .05) for leucine and 1.25 (95% CI, 0.96-1.61, P for trend = .06) for isoleucine. No statistically significant associations with each of the BCAA intake were observed for CRC-specific mortality (all P for trend > .30). Our findings suggest positive associations between higher intake of dietary BCAAs and risk of all-cause mortality in CRC patients. These findings need to be confirmed and potential mechanisms underlying this association need to be elucidated.
Abstract
What's new?
Animal protein sources such as meat and milk are high in branched-chain amino acids (BCAAs). BCAAs may potentially influence cancer progression by various mechanisms, including providing an energy source for tumor growth, and activation of the mTOR/p70S6K pathway. However, the impact of BCAAs on survival among patients with colorectal cancer (CRC) has been unclear. The results of this study suggest that higher intake of dietary BCAAs is associated with overall mortality risk in CRC patients.
CONFLICT OF INTEREST
Dr. Meyerhardt has received institutional research funding from Boston Biomedical, has served as an advisor/consultant to Ignyta and COTA Healthcare, and served on a grant review panel for the National Comprehensive Cancer Network funded by Taiho Pharmaceutical.
Open Research
DATA AVAILABILITY STATEMENT
Research data can be accessed by contacting the corresponding author of this work.
Supporting Information
| Filename | Description |
|---|---|
| ijc33449-sup-0001-Tables.pdfPDF document, 705.9 KB | Supplementary Table 1 Characteristics of colorectal cancer patients according to postdiagnosis total branched-chain amino acids (BCAA) intake by study Supplementary Table 2 Postdiagnostic BCAA intake and mortality among colorectal cancer patients among HPFS Supplementary Table 3 Postdiagnostic BCAA intake and mortality among colorectal cancer patients among NHS Supplementary Table 4 Postdiagnostic total BCAA intake and mortality among colorectal cancer patients after excluding 210 CRC patients with unspecified stage Supplementary Table 5 Proteins and main food sources of BCAAs and colorectal cancer specific and overall survival among NHS and HPFS |
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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