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Functional and clinical significance of variants localized to 8q24 in colon cancer.

ABSTRACT: Multiple genome-wide association studies have identified several susceptibility variants for colon cancer at 8q24. However, the functional roles of these variants have yet to be elucidated. Here, we evaluated the potential role of these markers in tumor progression and examined association with commonly observed structural abnormalities in this region, c-MYC amplification and chromosome fragility at FRA8C and FRA8D. We first replicated the previously reported association by testing 1,178 cases and 1,009 clinic-based controls with eight markers localized to three specific regions at 8q24. We observed significant associations with colon cancer risk with markers rs13254738 (ordinal odds ratio, 0.82; 95% confidence interval, 0.072-0.94; P(trend) = 0.0037) and rs6983267 (ordinal odds ratio, 1.17; 95% confidence interval, 1.03-1.32, P(trend) = 0.013). Survival analysis was done using a separate set of 460 cases to evaluate the clinical significance of these markers. Overall, univariate analysis did not detect survival differences for any of the markers. We also tested a subset of the 460 cases (n = 380) for structural abnormalities at or near the c-MYC locus using fluorescence in situ hybridization analysis. Furthermore, we evaluated a small number of cases homozygous for the rs6983267 alleles to test for differences in fragile site induction. None of the 8q markers correlated with amplification at the c-MYC locus as detected by fluorescence in situ hybridization, and no clear pattern of breakage was observed at the FRA8C and FRA8D sites. In this study, we confirm the association for several single nucleotide polymorphisms at 8q24 in colon cancer but have not detected any structural role relating to c-MYC amplification or chromosomal fragility. Finally, these risk alleles do not seem to be associated with survival.

SUBMITTER: Cicek MS

PROVIDER: S-EPMC4059694 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Functional and clinical significance of variants localized to 8q24 in colon cancer.

Cicek Mine S MS Slager Susan L SL Achenbach Sara J SJ French Amy J AJ Blair Hilary E HE Fink Stephanie R SR Foster Nathan R NR Kabat Brian F BF Halling Kevin C KC Cunningham Julie M JM Cerhan James R JR Jenkins Robert B RB Boardman Lisa A LA Petersen Gloria M GM Sargent Daniel J DJ Alberts Steven R SR Limburg Paul J PJ Thibodeau Stephen N SN

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20090818 9

Multiple genome-wide association studies have identified several susceptibility variants for colon cancer at 8q24. However, the functional roles of these variants have yet to be elucidated. Here, we evaluated the potential role of these markers in tumor progression and examined association with commonly observed structural abnormalities in this region, c-MYC amplification and chromosome fragility at FRA8C and FRA8D. We first replicated the previously reported association by testing 1,178 cases a ...[more]

PMID: 19690179

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Project description:Background:The association of miR-28-5p with colon cancer remains to be elucidated. This study aimed to determine the clinical significance and prognostic value of miR-28-5p in colon cancer. Methods:We retrospectively analyzed the data of miR-28-5p in colon adenocarcinoma data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and the data was divided into cancer group and normal group, respectively. Forty colon cancer tissues and adjacent normal tissues were collected and tested by qRT-PCR methods. The difference of the miR-28-5p expression between colon cancer and normal tissues was compared. The clinical significance of miR-28-5p in colon cancer and the association with the survival were determined. The predictive value of miR-28-5p in clinical features was determined using receiver operating characteristic curve. The target genes of miR-28-5p were identified, and the functional of target genes was performed using bioinformatics analysis. Results:: The expression of miR-28-5p was increased in colon cancer tissues compared with normal controls (p = 0.037). The expression of miR-28-5p was significantly increased in tissues with distant metastases compared with that without distant metastases (p = 0.026). Patients with high expression of miR-28-5p have a shorter survival time than those with low expression (p = 0.004). Cox analysis showed that miR-28-5p was an independent predictor for the survival of patients (p = 0.014). Combination of miR-28-5p with TNM stage and clinical stage can improve the prognostic value for the patients (p < 0.05). miR-28-5p has a moderate predictive value in predicting the TNM stage and clinical stage (T stage: AUC = 0.515; N stage: AUC = 0.523, M stage: AUC = 0.572; clinical stage: AUC = 0.539). 711 potential target genes of miR-28-5p were screened; their function and pathways were identified. Conclusions:: This study demonstrated that miR-28-5p was increased in colon cancer and can be an independent indicator for the overall survival in patients with colon cancer.

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Functional and clinical significance of variants localized to 8q24 in colon cancer.

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Functional and clinical significance of variants localized to 8q24 in colon cancer.

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