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.
PLoS One. 2012;7(7):e41954. doi: 10.1371/journal.pone.0041954. Epub 2012 Jul 27.
Low-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 FINDINGS: DNA 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/SIGNIFICANCE: We did not find evidence of association of CRC risk variants with patient survival.
低外显率遗传变异体越来越被认为会影响肿瘤发展的风险。结直肠癌（CRC）的风险变异体已定位到染色体位置 8q23.3、8q24、9p24.1、10p14、11q23、14q22.2、15q13、16q22.1、18q21、19q13.1 和 20p12.3。特别是 8q24 单核苷酸多态性（SNP）rs6983267，已被反复证实与 CRC 发病风险相关。由于 CRC 风险 SNP 也可能影响疾病结局，因此在本研究中，我们评估了它们是否影响患者的生存。
方法/主要发现：583 名 CRC 患者的 DNA 样本来自前瞻性北卡罗来纳癌症护理结果研究和监测联盟研究（NC CanCORS），这些患者的 11 个 CRC 易感性 SNP 在 6 个 CRC 风险基因座进行了基因分型。使用 Cox 回归分析评估基因型与患者生存之间的关系。在多变量分析中，与保护性等位基因相比，rs7013278 或 rs7014346（均位于 8q24）的 CRC 风险等位基因纯合子的患者总体生存率明显较差（危险比分别为 2.20 和 1.96；P<0.05）。然而，在进行多次检验校正后，这些关联均无统计学意义。测试的其他 9 个易感性 SNP 与生存无显著相关性。
结论/意义：我们没有发现 CRC 风险变异体与患者生存相关的证据。
