| People | Locations | Statistics |
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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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West, Hannah D.
in Cooperation with on an Cooperation-Score of 37%
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article
Relationship between 233 colorectal cancer risk loci and survival in 1926 patients with advanced disease
Abstract
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Genome, transcriptome and methylome-wide association studies have identified single-nucleotide polymorphisms (SNPs) or genes at 258 loci associated with colorectal cancer (CRC) risk. We studied the relationship between these and patient outcome.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We studied 1926 unrelated patients with advanced CRC from COIN and COIN-B. Of 205 CRC-risk SNPs, 19 were directly genotyped and 162 were imputed, and of 53 risk genes, 52 were tested. An additive Cox model for overall survival was adjusted for known prognostic factors. For nominally significant SNPs or genes, we considered a recessive model with a Bonferroni corrected threshold of <jats:italic>P</jats:italic> = 2.1 × 10<jats:sup>−4</jats:sup>. We examined SNPs as expression quantitative trait loci (eQTL) and the relationship between gene expression in colorectal tumours and survival in 597 unrelated patients.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Eleven SNPs or genes were nominally associated with survival under an additive model. Only rs117079142 mapping to <jats:italic>UTP23</jats:italic> and <jats:italic>EIF3H</jats:italic> (Hazard Ratio [HR] = 2.79, 95% Confidence Intervals [CI] = 1.70–4.58, <jats:italic>P</jats:italic> = 4.7 × 10<jats:sup>−5</jats:sup>) and rs9924886 mapping to <jats:italic>CDH1</jats:italic> and <jats:italic>CDH3</jats:italic> (HR = 1.24, 95% CI = 1.12–1.38, <jats:italic>P</jats:italic> = 5.2 × 10<jats:sup>−5</jats:sup>) passed the multiple testing threshold under a recessive model. rs117079142 was an eQTL for <jats:italic>UTP23</jats:italic> and rs9924886 for <jats:italic>CDH1</jats:italic>, <jats:italic>CDH3</jats:italic> and <jats:italic>ZFP90</jats:italic>. Decreased <jats:italic>CDH1</jats:italic> expression in CRCs was associated with worse survival (HR = 2.18, 95% CI = 1.3–3.5, <jats:italic>P</jats:italic> = 1.8 × 10<jats:sup>−3</jats:sup>).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>rs117079142 and rs9924886 may represent potential prognostic biomarkers for CRC.</jats:p></jats:sec>