Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 29, Issue 4, Pages 860-870Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-19-0891
Keywords
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Funding
- NIH-NCI [K99 CA215360]
- Skills Development Fellowship from the UK Medical Research Council [MR/P014054/1]
- CRUK Population Research Postdoctoral Fellowship [C52724/A20138]
- American Cancer Society [MRSG-17-220-01 -NEC]
- USNIH [K99 CA215314, R00 CA215314]
- Fred Hutchinson Cancer Research Center
- Centers for Disease Control and PreventionNational Program of Cancer Registries
- National Cancer Institute Surveillance Epidemiology and End Results program
- Hospital Clinical Research Program from the University Hospital Center of Nantes (CHU de Nantes) [PHRC-BRD09/C]
- Regional Council of Pays de la Loire
- Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC)
- Association Anne de Bretagne Genetique
- Ligue RegionaleContre le Cancer (LRCC)
- NIH [R01 CA60987, R01 CA48998, P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, R35 CA197735, K07 CA190673]
- NCI, NIH [U01 CA122839, R01 CA143247, U19 CA148107, U01 CA167551]
- Australasian Colorectal Cancer Family Registry (NCI/NIH) [U01 CA074778, U01/U24 CA097735]
- USC Consortium Colorectal Cancer Family Registry (NCI/NIH) [U01/U24 CA074799]
- Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH) [U01/U24 CA074800]
- Ontario Familial Colorectal Cancer Registry (NCI/NIH) [U01/U24 CA074783]
- Seattle Colorectal Cancer Family Registry (NCI/NIH) [U01/U24 CA074794]
- University of Hawaii Colorectal Cancer Family Registry (NCI/NIH) [U01/U24 CA074806]
- Surveillance, Epidemiology and End Results (SEER) Program of the NCI [N01-CN-67009, N01PC-35142, HHSN2612013000121]
- Hawai'i Department of Health [N01-PC-67001, N01-PC-35137, HHSN26120100037C]
- California Department of Public Health [HHSN261201000035C]
- German Research Council [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH117/1-1, HO5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1, BR 1704/17-1]
- Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany
- German Federal Ministry of Education and Research [01KH0404, 01ER0814, 01ER0815, 01ER1505A, 01ER1505B]
- NCI, NIH, U.S. Department of Health and Human Services [U01 CA164930, U01 CA137088, R01 CA059045]
- NIH/NCI Cancer Center Support Grant [P30 CA015704]
- Ontario Research Fund
- Canadian Institutes of Health Research
- Ontario Institute for Cancer Research, through Ontario Ministry of Research and Innovation
- Division of Cancer Prevention, National Cancer Institute, NIH, DHHS
- NIH, Genes, Environment and Health Initiative (GEI) [Z01 CP 010200, NIHU01 HG004446, NIHGEI U01 HG 004438]
- National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
- U.S. Public Health Service contracts from the National Cancer Institute [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]
- Matthias Lackas-Foundation
- German Consortium for Translational Cancer Research
- EU TRANSCAN initiative
- NCI/NIH, U.S. Department of Health and Human Services [U19 CA148107, R01 CA81488, P30 CA014089, R01 CA197350, P01 CA196569, R01 CA201407]
- National Institutes of Environmental Health Sciences, NIH [T32 ES013678]
- American Cancer Society
- Baden-Wurttemberg Ministry of Science, Research and Arts
- German Cancer Aid
- Damon Runyon Cancer Research Foundation [CI-8]
- NCI [R01CA136726]
- VicHealth
- Cancer Council Victoria
- Australian NHMRC [509348, 209057, 251553, 504711]
- NIH, U.S. Department of Health and Human Services [R01 CA81488]
- Robert and Kate Niehaus Center for Inherited Cancer Genomics
- Romeo Milio Foundation
- Florida Department of Health Bankhead-Coley Grant [09BN-13]
- University of South Florida Oehler Foundation
- Total Cancer Care Initiative
- Collaborative Data Services Core
- Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a National Cancer Institute-designated Comprehensive Cancer Center [P30 CA076292]
- Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research [CRT 43821]
- NIH, U.S. Department of Health and Human Serivces [U01 CA74783]
- National Cancer Institute of Canada [18223, 18226]
- Canadian Cancer Society Research Institute
- Cancer Research UK [C490/A16561]
- Instituto de Salud Carlos III
- FEDER funds -a way to build Europe [PI14-613, PI09-1286]
- Agency for Management of University and Research Grants (AGAUR) of the Catalan Government [2017SGR723]
- Junta de Castilla y Leon [LE22A10-2]
- Xarxa de Bancs de Tumors de Catalunya - Pla Director d'Oncologia de Catalunya (XBTC), Plataforma Biobancos [PT13/0010/0013]
- ICOBIOBANC - Catalan Institute of Oncology
- Swedish research council [K2015-55X-22674-01-4, K2008-55X-20157-03-3, K2006-72X-20157-01-2]
- Stockholm County Council (ALF project)
- Swedish Research Council/Infrastructure grant
- Swedish Cancer Foundation
- Karolinska Institute's Distinguished Professor Award
- UK National Institute for Health Research Biomedical Research Centers at the University of Cambridge
- [P50 CA127003]
- [P01 CA087969]
- [UM1 CA186107]
- [R01 CA042182]
- [R37 CA54281]
- [P01 CA033619]
- [R01 CA063464]
- [U01 CA164973]
- [U01 CA074783]
- [R01 CA076366]
- [K05 CA154337]
- [R01 CA189184]
- [U01 CA206110]
- [2P30CA015704-40]
- [R01 CA207371]
- NATIONAL CANCER INSTITUTE [ZIACP010195] Funding Source: NIH RePORTER
- MRC [MR/P014054/1, MC_UU_00011/6] Funding Source: UKRI
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Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 x 10(-4)] and alpha-linolenic acid (ORA(LA) = 0.95; 95% CI = 0.92-0.97; P = 5.4 x 10(-5)), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 x 10(-5)), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 x 10(-3)), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 x 10(-2)). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.
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