Journal Article

DKFZ-2023-01690

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study.

Pham, T. T. ; Nimptsch, K. ; Papadimitriou, N. ; Aleksandrova, K. ; Jenab, M. ; Gunter, M. J. ; Le Marchand, L. ; Li, L. ; Lynch, B. M. ; Castellví-Bel, S. ; Phipps, A. I. ; Schmit, S. L. ; Brenner, H.DKFZ* ; Ogino, S. ; Giovannucci, E. ; Pischon, T.

2023
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00432-023-05193-0

Abstract: Resistin, a novel pro-inflammatory protein implicated in inflammatory processes, has been suggested to play a role in colorectal development. However, evidence from observational studies has been inconsistent. Mendelian randomization may be a complementary method to examine this association.We conducted a two-sample Mendelian randomization to estimate the association between genetically determined circulating resistin concentrations and risk of colorectal cancer (CRC). Protein quantitative trait loci (pQTLs) from the SCALLOP consortium were used as instrumental variables (IVs) for resistin. CRC genetic summary data was obtained from GECCO/CORECT/CCFR (the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry), and FinnGen (Finland Biobank). The inverse variance weighted method (IVW) was applied in the main analysis, and other robust methods were used as sensitivity analyses. Estimates for the association from the two data sources were then pooled using a meta-analysis approach.Thirteen pQTLs were identified as IVs explaining together 7.80% of interindividual variation in circulating resistin concentrations. Based on MR analyses, genetically determined circulating resistin concentrations were not associated with incident CRC (pooled-IVW-OR per standard deviation of resistin, 1.01; 95% CI 0.96, 1.06; p = 0.67. Restricting the analyses to using IVs within or proximal to the resistin-encoding gene (cis-IVs), or to IVs located elsewhere in the genome (trans-IVs) provided similar results. The association was not altered when stratified by sex or CRC subsites.We found no evidence of a relationship between genetically determined circulating resistin concentrations and risk of CRC.

Keyword(s): Colorectal cancer ; Genetic ; Instrumental ; Mendelian randomization ; Resistin

Note: 2023 Nov;149(16):14889-14900

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Contributing Institute(s):

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

Research Program(s):

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

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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