Genome-wide scan of the effect of common nsSNPs on colorectal cancer survival outcome

Evropi Theodoratou, Susan M Farrington, Maria Timofeeva, Farhat V.N. Din, Victoria Svinti, Albert Tenesa, Tao Liu, Annika Lindblom, Steven Gallinger, Harry Campbell, Malcolm G Dunlop

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: We conducted a genome-wide scan to identify non-synonymous SNPs (nsSNPs) that might influence survival after a diagnosis of colorectal cancer (CRC).

METHODS: We genotyped 7679 nsSNPs in 1939 Scottish patients from the Scottish Colorectal Cancer Study recruited soon after a CRC diagnosis and prospectively followed for survival outcomes. All-cause and CRC-specific survival analyses were conducted using Cox proportional hazard models adjusted for stage, age and sex for all cancer cases, after cancer type stratification and assuming additive and recessive models of inheritance. For all the SNPs that had a p-value < 0.10 a meta-analysis was performed combining the results of the discovery set and a replication set of 899 Scottish CRC patients. The p-value threshold of significance was set as at p < 10-8.

RESULTS: 897 and 894 nsSNPs were associated with all-cause and CRC-specific mortality, respectively, at a p-value level < 0.10 in the discovery set. Meta-analysis of the results from the discovery and replication sets was performed overall and for cancers of colon and rectum separately and none of the variants reached a p-value < 10-8.

CONCLUSIONS: This large scale well-powered analysis demonstrates that common nsSNPs are not associated with CRC prognosis overall.

Original languageEnglish
Pages (from-to)988-993
Number of pages6
JournalBritish Journal of Cancer
Volume119
Issue number8
Early online date21 Aug 2018
DOIs
Publication statusE-pub ahead of print - 21 Aug 2018

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