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

ABSTRACT: 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?

SUBMITTER: Xu W

PROVIDER: S-EPMC4393623 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Xu Wei W Xu Jingxiong J Shestopaloff Konstantin K Dicks Elizabeth E Green Jane J Parfrey Patrick P Green Roger R Savas Sevtap S

Biomarker research 20150319

<h4>Background</h4>In this study we performed genome-wide association studies to identify candidate SNPs that may predict the risk of disease outcome in colorectal cancer.<h4>Methods</h4>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 stabl ...[more]

PMID: 25866641

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Project description:Interindividual variation in genetic background may influence the response to chemotherapy and overall survival for patients with advanced-stage non-small cell lung cancer (NSCLC).To identify genetic variants associated with poor overall survival in these patients, we conducted a genome-wide scan of 307,260 single-nucleotide polymorphisms (SNPs) in 327 advanced-stage NSCLC patients who received platinum-based chemotherapy with or without radiation at the University of Texas MD Anderson Cancer Center (the discovery population). A fast-track replication was performed for 315 patients from the Mayo Clinic followed by a second validation at the University of Pittsburgh in 420 patients enrolled in the Spanish Lung Cancer Group PLATAX clinical trial. A pooled analysis combining the Mayo Clinic and PLATAX populations or all three populations was also used to validate the results. We assessed the association of each SNP with overall survival by multivariable Cox proportional hazard regression analysis. All statistical tests were two-sided.SNP rs1878022 in the chemokine-like receptor 1 (CMKLR1) was statistically significantly associated with poor overall survival in the MD Anderson discovery population (hazard ratio [HR] of death = 1.59, 95% confidence interval [CI] = 1.32 to 1.92, P = 1.42 × 10(-6)), in the PLATAX clinical trial (HR of death = 1.23, 95% CI = 1.00 to 1.51, P = .05), in the pooled Mayo Clinic and PLATAX validation (HR of death = 1.22, 95% CI = 1.06 to 1.40, P = .005), and in pooled analysis of all three populations (HR of death = 1.33, 95% CI = 1.19 to 1.48, P = 5.13 × 10(-7)). Carrying a variant genotype of rs10937823 was associated with decreased overall survival (HR of death = 1.82, 95% CI = 1.42 to 2.33, P = 1.73 × 10(-6)) in the pooled MD Anderson and Mayo Clinic populations but not in the PLATAX trial patient population (HR of death = 0.96, 95% CI = 0.69 to 1.35).These results have the potential to contribute to the future development of personalized chemotherapy treatments for individual NSCLC patients.

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

Publications

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

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