Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Genome-wide search for determinants of survival in 1,926 patients with advanced colorectal cancer with follow-up in over 22,000 patients

Wills, Christopher, He, Yazhou, Summers, Matthew G., Lin, Yi, Phipps, Amanda I., Watts, Katie, Law, Philip J., Al-Tassan, Nada A., Maughan, Timothy S., Kaplan, Richard, Houlston, Richard S., Peters, Ulrike, Newcomb, Polly A., Chan, Andrew T., Buchanan, Daniel D., Gallinger, Steve, Marchand, Loic L., Pai, Rish K., Shi, Qian, Alberts, Steven R., Gray, Victoria, West, Hannah D., Escott-Price, Valentina, Dunlop, Malcolm G. and Cheadle, Jeremy 2021. Genome-wide search for determinants of survival in 1,926 patients with advanced colorectal cancer with follow-up in over 22,000 patients. European Journal Of Cancer 159 , pp. 247-258. 10.1016/j.ejca.2021.09.047
Item availability restricted.

[thumbnail of Figure 2] Image (JPEG) (Figure 2) - Accepted Post-Print Version
Restricted to Repository staff only

Download (1MB)
[thumbnail of Figure 3] Image (JPEG) (Figure 3) - Accepted Post-Print Version
Restricted to Repository staff only

Download (1MB)
[thumbnail of Figure 1] Image (JPEG) (Figure 1) - Accepted Post-Print Version
Restricted to Repository staff only

Download (1MB)
[thumbnail of EJC_Wills et al manuscript_and_tables_Revised (cleaned).pdf] PDF - Accepted Post-Print Version
Restricted to Repository staff only until 15 November 2022 due to copyright restrictions.
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (281kB)

Abstract

Background While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome. Patients and methods We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P < 1.0 × 10−5), we conducted sensitivity analyses based on the time from diagnosis to death and sought independent replications in 5675 patients from the Study of Colorectal Cancer in Scotland (SOCCS) and 16,964 patients from the International Survival Analysis in Colorectal cancer Consortium (ISACC). We analysed the Human Protein Atlas to determine if ERBB4 expression was associated with survival in 438 patients with colon adenocarcinomas. Results The most significant SNP associated with OS was rs79612564 in ERBB4 (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.16–1.32, P = 1.9 × 10−7). SNPs at 17 loci had suggestive associations for OS and all had similar effects on the time from diagnosis to death. No lead SNPs were independently replicated in the meta-analysis of all patients from SOCCS and ISACC. However, rs79612564 was significant in stage-IV patients from SOCCS (P = 2.1 × 10−2) but not ISACC (P = 0.89) and SOCCS combined with COIN and COIN-B attained genome-wide significance (P = 1.7 × 10−8). Patients with high ERBB4 expression in their colon adenocarcinomas had worse survival (HR = 1.50, 95% CI = 1.1–1.9, P = 4.6 × 10−2). Conclusions Genetic and expression data support a potential role for rs79612564 in the receptor tyrosine kinase ERBB4 as a predictive biomarker of survival.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0014-2964
Date of First Compliant Deposit: 4 November 2021
Date of Acceptance: 26 September 2021
Last Modified: 10 Dec 2021 00:37
URI: https://orca.cardiff.ac.uk/id/eprint/145293

Citation Data

Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics