Research

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

Ramachandran Meenakshisundaram¹ and Claudia Gragnoli^1,2,3,4,5

¹  Department of Medicine and Cellular & Molecular Physiology, Milton S. Hershey Medical Center, Hershey, PA, USA

²  Penn State University College of Medicine, Hershey, PA, USA

³  Sbarro Institute for Cancer Research & Molecular Medicine, Center for Biotechnology, Temple University's College of Science & Technology, Philadelphia, PA, USA

⁴  Department of Biology, Temple University's College of Science & Technology, Philadelphia, PA, USA

⁵  Molecular Biology Laboratory, Bios Biotech Multi-Diagnostic Health Center, Rome, Italy

author email corresponding author email

Journal of Experimental & Clinical Cancer Research 2009, 28:42doi:10.1186/1756-9966-28-42

Published:	28 March 2009

Abstract

Background

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.

Methods

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≥30 Kg/m² and 52 subjects had a BMI ≥ 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.

Results

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.

Conclusion

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.