The few studies that have been done to suggest that certain oncogenes, i.e., erbB2, K-ras, cyclin D1, and p53, are all altered in ways and in frequency similar to these phenomena in large bowel cancer.
In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival.
Over-representation of the CCND1 A allele was also seen in sporadic colorectal cancer cases compared to controls but this did not attain statistical significance (P=0.08).
In conclusion, beta-catenin protein dysregulation, but not k-ras mutation, appears to be required for cyclin D1 overexpression in colorectal carcinoma in vivo.
Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer.
Although the CCND1G870A polymorphism has been reported as a genetic risk factor for some tumour types, it does not appear to be linked to the risk of breast and colorectal cancers.
The aim of this study was to determine the frequency of CCND1 amplifications and gains in a large number of colorectal carcinomas, arranged in a tissue microarray, in order to assess their role in colorectal cancer development.
To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab.
One hundred and eleven specimens of colorectal carcinomas and adjacent normal colorectal mucosa were investigated by staining with a monoclonal antibody against cyclin D1 and by RT-PCR.
In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82-1.32) or adenoma (OR, 0.96; 95% CI, 0.79-1.18).
This investigation was designed to evaluate the effect of cyclin D1 gene polymorphism on the risk of colorectal cancer in Chinese migrants of the Taiwanese population.
Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association.
Matching serial sections of normal colonic epithelium and invasive CRCs (n = 32) were subjected to quantitative reverse transcriptase polymerase chain reaction specific to STAT3, cyclin D1, survivin, Bcl-xl and Mcl-1, as well as immunohistochemistry.
A meta-analyses including 11 published studies on CCND1G870A in addition to our study showed a slightly increased risk of CRC for carriers of the A allele (OR, 1.19; 95% CI, 1.06-1.34); however, there was some indication of publication bias.
In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR), 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003), cyclin D1 (adjusted OR, 1.57; P = .02), LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03), BRAF mutation (adjusted OR, 2.20; P = .04), and family history of colorectal cancer (adjusted OR, 0.64; P = .04) remained statistically significant.
In multivariate analysis, AURKA was associated with cyclin D1 expression (P = .010) and inversely with PIK3CA mutation (P=.014), fatty acid synthase expression (P=.028), and family history of colorectal cancer (P = .050), but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, beta-catenin, or cyclooxygenase 2.
Furthermore, the MDR analysis indicated that the best interactive model for CRC included three factors-CCND1G870A, caspase8 IVS12-19G/A, and caspase8 6 n del/ins-with 53.44% testing balanced accuracy and 10/10 cross-validation consistency, but the model was no longer significant after the 1000 times permutation test (P = 0.25).