Association of eleven common, low-penetrance colorectal cancer susceptibility genetic variants at six risk Loci with clinical outcome |
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Authors: | Janelle M Hoskins Pei-Shi Ong Temitope O Keku Joseph A Galanko Christopher F Martin Clint A Coleman Michelle Wolfe Robert S Sandler Howard L McLeod |
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Affiliation: | Division of Pharmacotherapy and Experimental Therapeutics, Institute for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America. |
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Abstract: | BackgroundLow-penetrance genetic variants have been increasingly recognized to influence the risk of tumor development. Risk variants for colorectal cancer (CRC) have been mapped to chromosome positions 8q23.3, 8q24, 9p24.1, 10p14, 11q23, 14q22.2, 15q13, 16q22.1, 18q21, 19q13.1 and 20p12.3. In particular, the 8q24 single nucleotide polymorphism (SNP), rs6983267, has reproducibly been associated with the risk of developing CRC. As the CRC risk SNPs may also influence disease outcome, thus in this study, we evaluated whether they influence patient survival.Methodology/Principal FindingsDNA samples from 583 CRC patients enrolled in the prospective, North Carolina Cancer Care Outcomes Research and Surveillance Consortium Study (NC CanCORS) were genotyped for 11 CRC susceptibility SNPs at 6 CRC risk loci. Relationships between genotypes and patient survival were examined using Cox regression analysis. In multivariate analysis, patients homozygous for the CRC risk allele of rs7013278 or rs7014346 (both at 8 q24) were only nominally significant for poorer overall survival compared to patients homozygous for the protective allele (hazard ratio = 2.20 and 1.96, respectively; P<0.05). None of these associations, however, remained statistically significant after correction for multiple testing. The other nine susceptibility SNPs tested were not significantly associated with survival.Conclusions/SignificanceWe did not find evidence of association of CRC risk variants with patient survival. |
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