Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
05
05
2020
revised:
21
06
2020
accepted:
18
09
2020
pubmed:
25
9
2020
medline:
22
12
2021
entrez:
24
9
2020
Statut:
ppublish
Résumé
Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
Sections du résumé
BACKGROUND
Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome.
METHODS
We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data.
RESULTS
Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex.
CONCLUSIONS
Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk.
IMPACT
These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
Identifiants
pubmed: 32967863
pii: 1055-9965.EPI-20-0651
doi: 10.1158/1055-9965.EPI-20-0651
pmc: PMC7710600
mid: NIHMS1632396
doi:
Substances chimiques
Fatty Acids, Omega-6
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2735-2739Subventions
Organisme : NCI NIH HHS
ID : R00 CA218892
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600003C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600001C
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600002C
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA182883
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600018C
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA182934
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA098870
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154823
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA237875
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA071789
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA247283
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA218892
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
Références
Genet Epidemiol. 2013 Nov;37(7):658-65
pubmed: 24114802
Am J Epidemiol. 2011 Dec 15;174(12):1373-81
pubmed: 22047824
Nat Commun. 2018 Feb 8;9(1):556
pubmed: 29422604
J Nutr. 2012 Jun;142(6):1067-73
pubmed: 22535760
Cancer Epidemiol Biomarkers Prev. 2020 Apr;29(4):860-870
pubmed: 32051193
PLoS Genet. 2011 Jul;7(7):e1002193
pubmed: 21829377
Pancreas. 2008 May;36(4):353-62
pubmed: 18437081
Circ Cardiovasc Genet. 2014 Jun;7(3):321-331
pubmed: 24823311