ABSTRACT
Cyclin-D1 (CCND1) belongs to the highly conserved cyclin family whose members are characterized by abundant expression during the cell cycle. As an oncogene, high level of CCND1 was observed and related to poor prognosis and tumor recurrence in many cancers. In this study, we focused on the role of CCND1 in the clinical outcome of clear cell renal cell carcinoma (ccRCC). Gene Expression Omnibus database, The Cancer Genome Atlas database, and immunohistochemical staining were used. The mRNA and protein levels of CCND1 were significantly enhanced in ccRCC tumor tissues. However, the low level of CCND1, but not high level of CCND1, was related to poor prognosis and tumor recurrence in ccRCC. Further analysis showed that CCND1 mRNA level decreased with increasing ccRCC tumor grades and the rate of recurrence in ccRCC patients. In a nomogram model, the CCND1 mRNA level was shown to help predict ccRCC patient recurrence. CCND1 is a strong determinant for prediction of recurrence. The patients with high CCND1 level appear to have a more favorable prognosis together with more frequent low-grade tumors and low rate of recurrence. This is the first study to investigate the prognostic roles of CCND1 in ccRCC and discovered that CCND1 had an unconventional positive impact on the clinical outcome of ccRCC patients.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Cyclin D1/genetics , Cyclin D1/metabolism , Down-Regulation , Kidney Neoplasms/diagnosis , Neoplasm Recurrence, Local/diagnosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Male , Neoplasm Grading , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Nomograms , PrognosisABSTRACT
BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of colorectal cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. MATERIALS AND METHODS: We systematically searched PubMed, EMBASES, Elsevier and Springer for relevant articles before Apr 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effects or random-effects models with Review Manager 5.0 software. RESULTS: A total of seven studies including 4,029 cases and 13,844 controls based on the search criteria were included for analysis. A significant association of the CHEK2 I157T C variant with unselected CRC was found (OR=1.61, 95% CI=1.40-1.87, P<0.001). We also found a significant association with sporadic CRC (OR=1.48, 95% CI=1.23-1.77, P<0.001) and separately with familial CRC (OR=1.97, 95% CI=1.41-2.74, P<0.001). CONCLUSION: This meta-analysis demonstrates that the CHEK2 I157T variant may be another important CRC-predisposing gene, which increases CRC risk, especially in familial CRC.
Subject(s)
Colorectal Neoplasms/etiology , Mutation/genetics , Protein Serine-Threonine Kinases/genetics , Checkpoint Kinase 2 , Genetic Predisposition to Disease , Humans , Meta-Analysis as Topic , Prognosis , Review Literature as Topic , Risk FactorsABSTRACT
BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of breast cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Elsevier and Springer for relevant articles published before Nov 2011. Summary odds ratio (OR) and 95% confidence interval (95% CI) incidence rates were calculated using a random-effects model with STATA (version 10.0) software. RESULTS: A total of fifteen case-control studies, including 19,621 cases and 27,001 controls based on the search criteria, were included for analysis. A significant association was found between carrying the CHEK2 I157T variant and increased risk of unselected breast cancer (OR = 1.48, 95% CI = 1.31-1.66, P < 0.0001), familial breast cancer (OR = 1.48, 95% CI = 1.16-1.89, P < 0.0001), and early-onset breast cancer (OR = 1.47, 95% CI = 1.29-1.66, P < 0.0001). We found an even stronger significant association between the CHEK2 I157T C variant and increased risk of lobular type breast tumors (OR = 4.17, 95% CI = 2.89-6.03, P < 0.0001). CONCLUSION: Our research indicates that the CHEK2 I157T variant may be another important genetic mutation which increases risk of breast cancer, especially the lobular type.
