Journal Article

DKFZ-2020-02371

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genotype-Based Gene Expression in Colon Tissue-Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients.

Deutelmoser, H. (First author)DKFZ* ; Lorenzo Bermejo, J. ; Benner, A.DKFZ* ; Weigl, K.DKFZ* ; Park, H. A.DKFZ* ; Haffa, M.DKFZ* ; Herpel, E. ; Schneider, M. ; Ulrich, C. M.DKFZ* ; Hoffmeister, M.DKFZ* ; Chang-Claude, J.DKFZ* ; Brenner, H.DKFZ* ; Scherer, D. (Last author)DKFZ*

2020
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: doi:10.3390/ijms21218150

Abstract: Colorectal cancer (CRC) survival has environmental and inherited components. The expression of specific genes can be inferred based on individual genotypes-so called expression quantitative trait loci. In this study, we used the PrediXcan method to predict gene expression in normal colon tissue using individual genotype data from 91 CRC patients and examined the correlation ρ between predicted and measured gene expression levels. Out of 5434 predicted genes, 58% showed a negative ρ value and only 16% presented a ρ higher than 0.10. We subsequently investigated the association between genotype-based gene expression in colon tissue for genes with ρ > 0.10 and survival of 4436 CRC patients. We identified an inverse association between the predicted expression of ARID3B and CRC-specific survival for patients with a body mass index greater than or equal to 30 kg/m2 (HR (hazard ratio) = 0.66 for an expression higher vs. lower than the median, p = 0.005). This association was validated using genotype and clinical data from the UK Biobank (HR = 0.74, p = 0.04). In addition to the identification of ARID3B expression in normal colon tissue as a candidate prognostic biomarker for obese CRC patients, our study illustrates the challenges of genotype-based prediction of gene expression, and the advantage of reassessing the prediction accuracy in a subset of the study population using measured gene expression data.

Note: #EA:C120#LA:C120#

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Contributing Institute(s):

1. Präventive Onkologie (C120)
2. C060 Biostatistik (C060)
3. C070 Klinische Epidemiologie und Alternf. (C070)
4. C020 Epidemiologie von Krebs (C020)
5. B280 Translationale funktionelle Krebsgenomik (B280)
6. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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