Abstract
BackgroundWe conducted a genome-wide scan to identify non-synonymous SNPs (nsSNPs) that might influence survival after a diagnosis of colorectal cancer (CRC).MethodsWe 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.Results897 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.ConclusionsThis large scale well-powered analysis demonstrates that common nsSNPs are not associated with CRC prognosis overall.
Highlights
Despite improvements in survival rates from colorectal cancer (CRC) over the last 25 years, deaths from CRC still account for~10% of all cancer deaths in the UK (Cancer Research UK, 2014)
A number of studies have generated associations between survival outcome and polymorphic genetic variants[6] and in others with combinations of genotype and particular treatments[7,8] In a previous study we examined whether Single nucleotide polymorphism (SNP)s influencing CRC risk had any effect on survival after diagnosis, and found that none of ten common genetic variants identified by genome-wide association studies (GWAS) were associated with survival from CRC,[9] (8q24,10,11 8q23.3,12 10p14,12 11q23,13 15q13,14 18q21,13,15 14q22.2,16 16q22.1,16 19q13.1,16 and 20p12.316), more recent studies have had conflicting and inconsistent results—
American Joint Committee on Cancer (AJCC) stage was strongly associated with all-cause and CRCspecific mortality in the discovery and replication sets
Summary
Despite improvements in survival rates from colorectal cancer (CRC) over the last 25 years, deaths from CRC still account for~10% of all cancer deaths in the UK (Cancer Research UK, 2014). 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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call