Abstract
Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile ¼ 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis ¼ 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported.
Original language | English (US) |
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Pages (from-to) | 4578-4590 |
Number of pages | 13 |
Journal | Cancer research |
Volume | 80 |
Issue number | 20 |
DOIs | |
State | Published - Oct 15 2021 |
ASJC Scopus subject areas
- Oncology
- Cancer Research
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Intake of dietary fruit, vegetables, and fiber and risk of colorectal cancer according to molecular subtypes : A pooled analysis of 9 studies. / Hidaka, Akihisa; Harrison, Tabitha A.; Cao, Yin et al.
In: Cancer research, Vol. 80, No. 20, 15.10.2021, p. 4578-4590.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Intake of dietary fruit, vegetables, and fiber and risk of colorectal cancer according to molecular subtypes
T2 - A pooled analysis of 9 studies
AU - Hidaka, Akihisa
AU - Harrison, Tabitha A.
AU - Cao, Yin
AU - Sakoda, Lori C.
AU - Barfield, Richard
AU - Giannakis, Marios
AU - Song, Mingyang
AU - Phipps, Amanda I.
AU - Figueiredo, Jane C.
AU - Zaidi, Syed H.
AU - Toland, Amanda E.
AU - Amitay, Efrat L.
AU - Berndt, Sonja I.
AU - Borozan, Ivan
AU - Chan, Andrew T.
AU - Gallinger, Steven
AU - Gunter, Marc J.
AU - Guinter, Mark A.
AU - Harlid, Sophia
AU - Hampel, Heather
AU - Jenkins, Mark A.
AU - Lin, Yi
AU - Moreno, Victor
AU - Newcomb, Polly A.
AU - Nishihara, Reiko
AU - Ogino, Shuji
AU - Obon-Santacana, Mireia
AU - Parfrey, Patrick S.
AU - Potter, John D.
AU - Slattery, Martha L.
AU - Steinfelder, Robert S.
AU - Um, Caroline Y.
AU - Wang, Xiaoliang
AU - Woods, Michael O.
AU - van Guelpen, Bethany
AU - Thibodeau, Stephen N.
AU - Hoffmeister, Michael
AU - Sun, Wei
AU - Hsu, Li
AU - Buchanan, Daniel D.
AU - Campbell, Peter T.
AU - Peters, Ulrike
N1 - Funding Information: EPIC: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Natio-nale, Institut National de la Santéet de la Recherche Médicale (INSERM, France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungs-zentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); ERC-2009-AdG Funding Information: Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR; X01-HG008596 and X-01-HG007585). CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268201200008I. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. Funding Information: This work was supported by the Uehara Memorial Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA164930, U01 CA137088, R01 CA059045, U01 CA164930, R21 CA191312, and R01 CA201407). Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR; X01-HG008596 and X-01-HG007585). CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268201200008I. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. The Colon Cancer Family Registry (CCFR, www.coloncfr.org) was supported in part by funding from the NCI, NIH (award U01 CA167551) and through U01/U24 cooperative agreements from NCI with the following CCFR centers: Australasian (CA074778 and CA097735), Ontario (OFCCR,CA074783), Seattle (SFCCR, CA074794 and R01 CA076366 to P.A. Newcomb), and the Mayo Clinic (CA074800). Support for case ascertainment was provided in part from the Surveillance, Epidemiology, and End Results (SEER) Program, the Minnesota Cancer Surveillance System (MCSS), the Victoria Cancer Registry (Australia), and the Ontario Cancer Registry (Canada).The content of this article does not necessarily reflect the views or policies of the NIH or any of the collaborating centers in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government, any cancer registry, or the CCFR. CPS-II: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. This study was conducted with Institutional Review Board approval. DALS: NIH (R01 CA48998 to M.L. Slattery). EPIC: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM, France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020, Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska ne and Vasterbotten (Sweden). Harvard cohorts [HPFS, NHS: HPFS is supported by the NIH (P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, R35 CA197735, K07 CA190673, and P50 CA127003)], NHS by the NIH (R01 CA137178, P01 CA087969, UM1 CA186107, R01 CA151993, R35 CA197735, K07 CA190673, and P50 CA127003). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 509348, 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. NFCCR: This work was supported by an Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821), the NIH, U.S. Department of Health and Human Services (U01 CA74783), and National Cancer Institute of Canada grants (18223 and 18226). The authors wish to acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Genome Quebec Innovation Centre, Montreal, Canada, for genotyping the Sequenom panel in the NFCCR samples. Funding was provided to Michael O. Woods by the Canadian Cancer Society Research Institute. NSHDS: Swedish Research Council, Swedish Cancer Society, Cutting-Edge Research Grant and other grants from Region Vasterbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation at Umea University, the Cancer Research Foundation in Northern Sweden, and the Faculty of Medicine, Umea University, Umea, Sweden. CCFR: The Colon CFR graciously thanks the generous contributions of their 42,505 study participants, dedication of study staff, and the financial support from the U.S. National Cancer Institute, without which this important registry would not exist. CPS-II: The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. Harvard cohorts (HPFS, NHS, and PHS): The study protocol was approved by the Institutional Review Boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. We would like to thank the participants and staff of the HPFS, NHS, and PHS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. NSHDS investigators thank the Biobank Research Unit at Umea University, the Vasterbotten Intervention Programme, the Northern Sweden MONICA study, and Region Vasterbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council (VR 2017-00650). Funding Information: L.C. Sakoda reports grants from National Cancer Institute during the conduct of the study. M. Giannakis reports grants from Bristol Myers-Squibb and grants from Merck outside the submitted work. A.E. Toland reports grants from National Institutes of Health during the conduct of the study. A.T. Chan reports grants and personal fees from Bayer Pharma AG, personal fees from Pfizer Inc., personal fees from Janssen Pharmaceuticals, and personal fees from Boehringer Ingelheim outside the submitted work. H. Hampel reports other aid from Myriad Genetic Laboratories, Inc. (free genetic testing for a subset of patients on this study) during the conduct of the study; personal fees from Invitae Genetics (Scientific Advisory Board), personal fees from Promega (Medical Advisory Board), personal fees from Genome Medical (Scientific Advisory Board), and personal fees from 23andMe (consulting) outside the submitted work. M.A. Jenkins reports grants from NCI (funding to my institution) outside the submitted work. V. Moreno reports grants from Agency for Management of University and Research Grants (AGAUR) of the Catalan Government and grants from Instituto de Salud Carlos III during the conduct of the study. R. Nishihara reports personal fees from Pfizer (current employer) outside the submitted work. S. Ogino reports grants from National Institutes of Health (grant number R35 CA197735) and grants from National Institutes of Health (grant number R01 CA151993) during the conduct of the study. P.S. Parfrey reports grants from Canadian Institutes Health Research during the conduct of the study. B. Van Guelpen reports grants from the Swedish Research Council, grants from the Swedish Cancer Society, grants from the Knut and Alice Wallenberg Foundation, grants from the Lion's Cancer Research Foundation at Umea° University, grants from the Cancer Research Foundation in Northern Sweden, and grants from Region V€asterbotten during the conduct of the study. No potential conflicts of interest were disclosed by the other authors. Funding Information: This work was supported by the Uehara Memorial Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Funding Information: The Colon Cancer Family Registry (CCFR, www.coloncfr.org) was supported in part by funding from the NCI, NIH (award U01 CA167551) and through U01/U24 cooperative agreements from NCI with the following CCFR centers: Australasian (CA074778 and CA097735), Ontario (OFCCR,CA074783), Seattle (SFCCR, CA074794 and R01 CA076366 to P.A. Newcomb), and the Mayo Clinic (CA074800). Support for case ascertainment was provided in part from the Surveillance, Epidemiology, and End Results (SEER) Program, the Minnesota Cancer Surveillance System (MCSS), the Victoria Cancer Registry (Australia), and the Ontario Cancer Registry (Canada).The content of this article does not necessarily reflect the views or policies of the NIH or any of the collaborating centers in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government, any cancer registry, or the CCFR. Publisher Copyright: © 2020 American Association for Cancer Research.
PY - 2021/10/15
Y1 - 2021/10/15
N2 - Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile ¼ 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis ¼ 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported.
AB - Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile ¼ 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis ¼ 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported.
UR - http://www.scopus.com/inward/record.url?scp=85100395350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100395350&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-20-0168
DO - 10.1158/0008-5472.CAN-20-0168
M3 - Article
C2 - 32816852
AN - SCOPUS:85100395350
VL - 80
SP - 4578
EP - 4590
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 20
ER -