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.
Highlights
Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States
The present study was performed to examine the prognostic significance of 11 common, low-penetrance genetic variants at 6 colorectal cancer (CRC) loci that have been previously reported to predispose individuals to CRC [8,9,10,11,12,13,14,15,16,17]
We found marginal significance between two single nucleotide polymorphism (SNP), rs7013278 and rs7014346 (HR = 2.20, P = 0.01 and hazard ratio (HR) = 1.96, P = 0.03 respectively), with inferior CRC survival by multivariate regression analysis, none of these variants showed study-wide association with survival after correction for multiple testing
Summary
Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States. Despite improvements in treatment modalities, the 5-year survival rate for CRC patients ranges from 10–90% [1]. This huge variation in clinical outcome is due, in part, to the fact that CRC is a heterogeneous disease comprising discrete subsets that evolve through multiple different etiologies. Both germline and somatic genetic alterations can be involved in the malignant transformation of normal colon cells. As the CRC risk SNPs may influence disease outcome, in this study, we evaluated whether they influence patient survival
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