Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma |
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| Authors: | Moubin Lin MD PhD Cathy Eng MD Ernest T Hawk MD Maosheng Huang MD Jie Lin PhD Jian Gu PhD Lee M Ellis MD Xifeng Wu MD PhD |
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| Institution: | 1. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas;2. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;3. Division of Cancer Prevention and Population Science, The University of Texas MD Anderson Cancer Center, Houston, Texas;4. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;5. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas;6. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TexasFax: (713) 792‐4657 |
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| Abstract: | BACKGROUND: Ultraconserved elements (UCEs) are noncoding genomic sequences that completely identical among human, mouse, and rat species and harbor critical biologic functions. The authors hypothesized that single nucleotide polymorphisms (SNPs) within UCEs are associated with clinical outcomes in patients with colorectal cancer (CRC). METHODS: Forty‐eight SNPs within UCEs were genotyped in 662 patients with stage I through III CRC. The associations between genotypes and recurrence and survival were analyzed in patients with stage II or III CRC who received fluoropyrimidine‐based adjuvant chemotherapy using a training and validation design. The training set included 115 patients with stage II disease and 170 patients with stage III disease, and the validation set included 88 patients with stage II disease and 112 patients with stage III disease. RESULTS: Eight SNPs were associated with clinical outcomes stratified by disease stage. In particular, for patients with stage II CRC who had at least 1 variant allele of reference SNP sequence 7849 (rs7849), a consistent association with increased recurrence risk was observed in the training set (hazard ratio HR], 2.39; 95% confidence interval CI], 1.04‐5.52), in the replication set (HR, 3.70; 95% CI, 1.42‐9.64), and in a meta‐analysis (HR, 2.89; 95% CI, 1.54‐5.41). Several other SNPs were significant in the training set but not in the validation set. These included rs2421099, rs16983007, and rs10211390 for recurrence and rs6590611 for survival in patients with stage II disease; and SNPs rs6124509 and rs11195893 for recurrence in patients with stage III disease. In addition, a significant cumulative effect was observed of multiple risk genotypes and potential gene‐gene interactions on recurrence risk. CONCLUSIONS: To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5‐fluorouracil–based chemotherapy. Cancer 2012. © 2012 American Cancer Society. |
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| Keywords: | single nucleotide polymorphism ultraconserved elements colorectal cancer recurrence |
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