Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.
Mendelian randomization
colorectal cancer
genes
nutrition
supplements
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
16
07
2020
accepted:
04
01
2021
pubmed:
20
3
2021
medline:
29
6
2021
entrez:
19
3
2021
Statut:
ppublish
Résumé
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
Sections du résumé
BACKGROUND
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.
OBJECTIVES
To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).
METHODS
Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.
RESULTS
Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.
CONCLUSIONS
These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
Identifiants
pubmed: 33740060
pii: S0002-9165(22)00728-6
doi: 10.1093/ajcn/nqab003
pmc: PMC8168352
doi:
Substances chimiques
Micronutrients
0
Selenium
H6241UJ22B
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1490-1502Subventions
Organisme : NCI NIH HHS
ID : U01 CA182883
Pays : United States
Organisme : Cancer Research UK
ID : 29186
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U01 CA206110
Pays : United States
Organisme : Cancer Research UK
ID : 29019
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/3
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 19167
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244588
Pays : United States
Organisme : Cancer Research UK
ID : C18281/A19169
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207371
Pays : United States
Organisme : Cancer Research UK
ID : 16561
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 25004
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 19169
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.
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