CDK4 IVS4-nt40 AA genotype and obesity-associated tumors/cancer in Italians - a case-control study

Cell cycle checkpoint regulation is crucial for prevention of tumor in mammalian cells. Cyclin-dependant kinase 4 (CDK4) is important in cell cycle regulation, as it controls the G1-S phase of the cell cycle. CDK4 has potential mitogenic properties through phosphorylation of target proteins. We aimed at identifying a role of CDK4 IVS4-nt40 G-->A gene variant in benign and/or malignant tumors and in obesity-associated benign and/or malignant tumors in an Italian adult subject dataset.

We recruited 263 unrelated Italian subjects: 106 subjects had at least one benign tumor and 46 subjects had at least one malignant tumor, while 116 subjects had at least two tumors and/or cancers. We collected BMI data for 90% of them: 186 subjects had a BMI>or=30 Kg/m2 and 52 subjects had a BMI >or= 30 Kg/m2. We performed statistical power calculations in our datasets. DNA samples were directly sequenced with specific primers for the CDK4 IVS4-nt40 G-->A variant. Genotype association tests with disease were performed.

In our study, no significant association of the CDK4 IVS4-nt40 AA genotype with cancer and/or tumors/cancer are/is detected. However, the CDK4 IVS4-nt40 AA genotype is significantly associated with cancer and tumors/cancer in obese patients.

This finding is interesting since obesity is a risk factor for tumors and cancer. This study should prompt further work aiming at establishing the role of CDK4 in contributing to tumor/cancer genetic risk predisposition, as well as its role as a potentially effective therapeutic target gene for obesity-associated tumor/cancer management.