Relationship between 233 colorectal cancer risk loci and survival in 1,926 patients with advanced disease

Wills, Christopher, Houseman, Amy, Watts, Katie, Maughan, Timothy S., Fisher, David, Houlston, Richard S., West, Hannah D. ORCID: https://orcid.org/0000-0002-6104-6534, Escott Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483 and Cheadle, Jeremy P. ORCID: https://orcid.org/0000-0001-9453-8458 2023. Relationship between 233 colorectal cancer risk loci and survival in 1,926 patients with advanced disease. BJC Reports 1 , 2. 10.1038/s44276-023-00003-z

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Abstract

Background: 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. Methods: 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 P = 2.1 × 10−4. We examined SNPs as expression quantitative trait loci (eQTL) and the relationship between gene expression in colorectal tumours and survival in 597 unrelated patients. Results: Eleven SNPs or genes were nominally associated with survival under an additive model. Only rs117079142 mapping to UTP23 and EIF3H (Hazard Ratio [HR] = 2.79, 95% Confidence Intervals [CI] = 1.70–4.58, P = 4.7 × 10−5) and rs9924886 mapping to CDH1 and CDH3 (HR = 1.24, 95% CI = 1.12–1.38, P = 5.2 × 10−5) passed the multiple testing threshold under a recessive model. rs117079142 was an eQTL for UTP23 and rs9924886 for CDH1, CDH3 and ZFP90. Decreased CDH1 expression in CRCs was associated with worse survival (HR = 2.18, 95% CI = 1.3–3.5, P = 1.8 × 10−3). Conclusion: rs117079142 and rs9924886 may represent potential prognostic biomarkers for CRC.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature
ISSN:	2731-9377
Date of First Compliant Deposit:	8 June 2023
Date of Acceptance:	12 May 2023
Last Modified:	31 Jul 2023 16:51
URI:	https://orca.cardiff.ac.uk/id/eprint/160240

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