Journal Article

DKFZ-2021-00667

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Tsilidis, K. K. ; Papadimitriou, N. ; Dimou, N. ; Gill, D. ; Lewis, S. J. ; Martin, R. M. ; Murphy, N. ; Markozannes, G. ; Zuber, V. ; Cross, A. J. ; Burrows, K. ; Lopez, D. S. ; Key, T. J. ; Travis, R. C. ; Perez-Cornago, A. ; Hunter, D. J. ; van Duijnhoven, F. J. B. ; Albanes, D. ; Arndt, V.DKFZ* ; Berndt, S. I. ; Bézieau, S. ; Bishop, D. T. ; Boehm, J. ; Brenner, H.DKFZ* ; Burnett-Hartman, A. ; Campbell, P. T. ; Casey, G. ; Castellví-Bel, S. ; Chan, A. T. ; Chang-Claude, J.DKFZ* ; de la Chapelle, A. ; Figueiredo, J. C. ; Gallinger, S. J. ; Giles, G. G. ; Goodman, P. J. ; Gsur, A. ; Hampe, J. ; Hampel, H. ; Hoffmeister, M.DKFZ* ; Jenkins, M. A. ; Keku, T. O. ; Kweon, S.-S. ; Larsson, S. C. ; Le Marchand, L. ; Li, C. I. ; Li, L. ; Lindblom, A. ; Martín, V. ; Milne, R. L. ; Moreno, V. ; Nan, H. ; Nassir, R. ; Newcomb, P. A. ; Offit, K. ; Pharoah, P. D. P. ; Platz, E. A. ; Potter, J. D. ; Qi, L. ; Rennert, G. ; Sakoda, L. C. ; Schafmayer, C. ; Slattery, M. L. ; Snetselaar, L. ; Schenk, J. ; Thibodeau, S. N. ; Ulrich, C. M. ; Van Guelpen, B. ; Harlid, S. ; Visvanathan, K. ; Vodickova, L. ; Wang, H. ; White, E. ; Wolk, A. ; Woods, M. O. ; Wu, A. H. ; Zheng, W. ; Bueno-de-Mesquita, B. ; Boutron-Ruault, M.-C. ; Hughes, D. J. ; Jakszyn, P. ; Kühn, T.DKFZ* ; Palli, D. ; Riboli, E. ; Giovannucci, E. L. ; Banbury, B. L. ; Gruber, S. B. ; Peters, U. ; Gunter, M. J.

2021
Oxford University Press Oxford

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Please use a persistent id in citations: doi:10.1093/ajcn/nqab003

Abstract: 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.

Keyword(s): Mendelian randomization ; colorectal cancer ; genes ; nutrition ; supplements

Note: 113(6):1490-1502

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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