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Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Authors :
Tsilidis KK
Papadimitriou N
Dimou N
Gill D
Lewis SJ
Martin RM
Murphy N
Markozannes G
Zuber V
Cross AJ
Burrows K
Lopez DS
Key TJ
Travis RC
Perez-Cornago A
Hunter DJ
van Duijnhoven FJB
Albanes D
Arndt V
Berndt SI
Bézieau S
Bishop DT
Boehm J
Brenner H
Burnett-Hartman A
Campbell PT
Casey G
Castellví-Bel S
Chan AT
Chang-Claude J
de la Chapelle A
Figueiredo JC
Gallinger SJ
Giles GG
Goodman PJ
Gsur A
Hampe J
Hampel H
Hoffmeister M
Jenkins MA
Keku TO
Kweon SS
Larsson SC
Le Marchand L
Li CI
Li L
Lindblom A
Martín V
Milne RL
Moreno V
Nan H
Nassir R
Newcomb PA
Offit K
Pharoah PDP
Platz EA
Potter JD
Qi L
Rennert G
Sakoda LC
Schafmayer C
Slattery ML
Snetselaar L
Schenk J
Thibodeau SN
Ulrich CM
Van Guelpen B
Harlid S
Visvanathan K
Vodickova L
Wang H
White E
Wolk A
Woods MO
Wu AH
Zheng W
Bueno-de-Mesquita B
Boutron-Ruault MC
Hughes DJ
Jakszyn P
Kühn T
Palli D
Riboli E
Giovannucci EL
Banbury BL
Gruber SB
Peters U
Gunter MJ
Source :
The American journal of clinical nutrition [Am J Clin Nutr] 2021 Jun 01; Vol. 113 (6), pp. 1490-1502.
Publication Year :
2021

Abstract

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.<br />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).<br />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.<br />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.<br />Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.<br /> (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Details

Language :
English
ISSN :
1938-3207
Volume :
113
Issue :
6
Database :
MEDLINE
Journal :
The American journal of clinical nutrition
Publication Type :
Academic Journal
Accession number :
33740060
Full Text :
https://doi.org/10.1093/ajcn/nqab003