Genome-wide scan of the effect of common nsSNPs on colorectal cancer survival outcome. Issue 8 (16th October 2018)

• Record Type: Journal Article
• Authors: Theodoratou, Evropi; Farrington, Susan; Timofeeva, Maria; Din, Farhat; Svinti, Victoria; Tenesa, Albert; Liu, Tao; Lindblom, Annika; Gallinger, Steven; Campbell, Harry; Dunlop, Malcolm
• Is Part Of: British journal of cancer. Volume 119:Issue 8(2018)
• Page Start: 988
• Page End: 993
• Publication Date: 2018-10-16
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; Tumors -- Periodicals; 616.994
• DOI: 10.1038/s41416-018-0117-7
• Languages: English
• ISSNs: 0007-0920

Abstract

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 ap -value < 0.10 a meta-analysis was performed combining the results of the discovery set and a replication set of 899 Scottish CRC patients. Thep -value threshold of significance was set as atp < 10−8 . Results 897 and 894 nsSNPs were associated with all-cause and CRC-specific mortality, respectively, at ap -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 ap -value < 10−8 . Conclusions This large scale well-powered analysis demonstrates that common nsSNPs are not associated with CRC prognosis overall.