A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer

We aimed to examine the associations of a genome‐wide set of single nucleotide polymorphisms (SNPs) and 254 copy number variations (CNVs) and/or insertion/deletions (INDELs) with clinical outcomes in colorectal cancer patients (n = 505). We also aimed to investigate whether their associations change...

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Autores principales:	Yajun Yu, Salem Werdyani, Megan Carey, Patrick Parfrey, Yildiz E. Yilmaz, Sevtap Savas
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	colorectal cancer genetic variants genome‐wide association study prognostic markers proportional hazards (PH) assumption variables with time‐varying associations Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f38115ceccda493d92cbea0b37025eff
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spelling	oai:doaj.org-article:f38115ceccda493d92cbea0b37025eff2021-12-02T10:31:06ZA comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer1878-02611574-789110.1002/1878-0261.13067https://doaj.org/article/f38115ceccda493d92cbea0b37025eff2021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13067https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261We aimed to examine the associations of a genome‐wide set of single nucleotide polymorphisms (SNPs) and 254 copy number variations (CNVs) and/or insertion/deletions (INDELs) with clinical outcomes in colorectal cancer patients (n = 505). We also aimed to investigate whether their associations changed (e.g., appeared, diminished) over time. Multivariable Cox proportional hazards and piece‐wise Cox regression models were used to examine the associations. The Cancer Genome Atlas (TCGA) datasets were used for replication purposes and to examine the gene expression differences between tumor and nontumor tissue samples. A common SNP (WBP11‐rs7314075) was associated with disease‐specific survival with P‐value of 3.2 × 10−8. Association of this region with disease‐specific survival was also detected in the TCGA patient cohort. Two expression quantitative trait loci (eQTLs) were identified in this locus that were implicated in the regulation of ERP27 expression. Interestingly, expression levels of ERP27 and WBP11 were significantly different between colorectal tumors and nontumor tissues. Three SNPs predicted the risk of recurrent disease only after 5 years postdiagnosis. Overall, our study identified novel variants, one of which also showed an association in the TCGA dataset, but no CNVs/INDELs, that associated with outcomes in colorectal cancer. Three SNPs were candidate predictors of long‐term recurrence/metastasis risk.Yajun YuSalem WerdyaniMegan CareyPatrick ParfreyYildiz E. YilmazSevtap SavasWileyarticlecolorectal cancergenetic variantsgenome‐wide association studyprognostic markersproportional hazards (PH) assumptionvariables with time‐varying associationsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3329-3347 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer genetic variants genome‐wide association study prognostic markers proportional hazards (PH) assumption variables with time‐varying associations Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer genetic variants genome‐wide association study prognostic markers proportional hazards (PH) assumption variables with time‐varying associations Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yajun Yu Salem Werdyani Megan Carey Patrick Parfrey Yildiz E. Yilmaz Sevtap Savas A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer
description	We aimed to examine the associations of a genome‐wide set of single nucleotide polymorphisms (SNPs) and 254 copy number variations (CNVs) and/or insertion/deletions (INDELs) with clinical outcomes in colorectal cancer patients (n = 505). We also aimed to investigate whether their associations changed (e.g., appeared, diminished) over time. Multivariable Cox proportional hazards and piece‐wise Cox regression models were used to examine the associations. The Cancer Genome Atlas (TCGA) datasets were used for replication purposes and to examine the gene expression differences between tumor and nontumor tissue samples. A common SNP (WBP11‐rs7314075) was associated with disease‐specific survival with P‐value of 3.2 × 10−8. Association of this region with disease‐specific survival was also detected in the TCGA patient cohort. Two expression quantitative trait loci (eQTLs) were identified in this locus that were implicated in the regulation of ERP27 expression. Interestingly, expression levels of ERP27 and WBP11 were significantly different between colorectal tumors and nontumor tissues. Three SNPs predicted the risk of recurrent disease only after 5 years postdiagnosis. Overall, our study identified novel variants, one of which also showed an association in the TCGA dataset, but no CNVs/INDELs, that associated with outcomes in colorectal cancer. Three SNPs were candidate predictors of long‐term recurrence/metastasis risk.
format	article
author	Yajun Yu Salem Werdyani Megan Carey Patrick Parfrey Yildiz E. Yilmaz Sevtap Savas
author_facet	Yajun Yu Salem Werdyani Megan Carey Patrick Parfrey Yildiz E. Yilmaz Sevtap Savas
author_sort	Yajun Yu
title	A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer
title_short	A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer
title_full	A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer
title_fullStr	A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer
title_full_unstemmed	A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer
title_sort	comprehensive analysis of snps and cnvs identifies novel markers associated with disease outcomes in colorectal cancer
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/f38115ceccda493d92cbea0b37025eff
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A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer

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