A genome wide association study on Newfoundland colorectal cancer patients’ survival outcomes

Biomarker Research

Wei Xu²  Jingxiong Xu²  Konstantin Shestopaloff²  Elizabeth Dicks¹  Jane Green⁴  Patrick Parfrey¹  Roger Green⁴  Sevtap Savas³ 

[1] Clinical Epidemiology Unit, Faculty of Medicine, Memorial University, St. John’s A1B 3V6NL, Canada

[2] Dalla Lana School of Public Health, University of Toronto, Toronto M5T 3M7ON, Canada

[3] Discipline of Oncology, Faculty of Medicine, Memorial University, St. John’s A1B 3 V6NL, Canada

[4] Discipline of Genetics, Faculty of Medicine, Memorial University, St. John’s A1B 3 V6NL, Canada

关键词: Clinical outcome;    Survival analyses;    SNP;    Genome-wide;    Colorectal cancer;   

Others  :  1170516
DOI  :  10.1186/s40364-015-0031-6

 received in 2014-11-21, accepted in 2015-02-23,  发布年份 2015

【 摘 要 】

Background

In this study we performed genome-wide association studies to identify candidate SNPs that may predict the risk of disease outcome in colorectal cancer.

Methods

Patient cohort consisted of 505 unrelated patients with Caucasian ancestry. Germline DNA samples were genotyped using the Illumina® human Omni-1quad SNP chip. Associations of SNPs with overall and disease free survivals were examined primarily for 431 patients with microsatellite instability-low (MSI-L) or stable (MSS) colorectal tumors using Cox proportional hazards method adjusting for clinical covariates. Bootstrap method was applied for internal validation of results. As exploratory analyses, association analyses for the colon (n = 334) and rectal (n = 171) cancer patients were also performed.

Results

As a result, there was no SNP that reached the genomewide significance levels (p < 5x10⁻⁸) in any of the analyses. A small number of genetic markers (n = 10) showed nominal associations (p <10⁻⁶) for MSS/MSI-L, colon, or rectal cancer patient groups. These markers were located in two non-coding RNA genes or intergenic regions and none were amino acid substituting polymorphisms. Bootstrap analysis for the MSS/MSI-L cohort data suggested the robustness of the observed nominal associations.

Conclusions

Likely due to small number of patients, our study did not identify an acceptable level of association of SNPs with outcome in MSS/MSI-L, colon, or rectal cancer patients. A number of SNPs with sub-optimal p-values were, however, identified; these loci may be promising and examined in other larger-sized patient cohorts.

【 授权许可】

   
2015 Xu et al.; licensee BioMed Central.

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