The chromosome 12q12-q14 region has been shown by a genome scan to be in linkage to bladder cancer [5], as well as to obesity-associated type 2 diabetes genes [6]. Previous studies have reported differential CDK4 expression in tumors such as gliosarcoma, mantle cell lymphoma and squamous cell carcinoma [7–9]. However, no study has up to date investigated

the CDK4 variant in the human genome of cancer patients to prove their potential role buy Enzalutamide in oncogenic pathogenesis. This study was carried out to find out whether there is any association of CDK4 IVS4-nt40 G→A SNP with cancer and/or tumors/cancer as well as with obesity-associated cancer and/or tumors/cancer in the Italian population. Materials and methods We recruited from Italy a total of 263 unrelated adult subjects from the general population. We carried out the study with the written informed consent from each subject and with the approval from the Institutional

Review Board, in accordance with the Helsinki Declaration guidelines. We collected clinical information on the presence or absence of tumors and/or cancer on the total 263 subjects. Among 263 subjects, 152 subjects (58%) presented with either benign and/or malignant tumors: among these, 106 subjects had at least one benign tumor and 46 subjects had at least one malignant tumor, while 116 subjects had at least Sotrastaurin two tumors and/or cancer. The various tumor and cancer types are described in Table 1. Table 1 Number of tumors/cancers types Site Tumor Cancer Skin 1 6 Oral

cavity 1 1 RT including lungs 2 2 GIT 8 8 Hormonal 67 22 Thyroid 29 1 Hematological 1 5 Brain 3 1 Endocrine 2 0 RT = Respiratory tract, GIT = Gastrointestinal tract (liver, colon and pancreas), Hormonal-dependent = Breast, Ovary, Uterus, Prostate In the subject group, we collected BMI data for 90% of subjects: 186 subjects had a BMI less than 30 Kg/m2 and 52 subjects had a BMI≥30 Kg/m2, thus the latter met the definition for obesity. DNA samples were directly sequenced by PCR and automated fluorescence sequencer with specific Fluorometholone Acetate primers for the CDK4 IVS4-nt40 G→A single nucleotide polymorphism (SNP). True detectable odds ratios (ORs) for genotype association tests were calculated in our datasets with statistical power at least 60%, type 1 error probability of 0.05, and given, in the general Italian population, a cancer prevalence of 2.7% [10] and, in the obese Italian population, of 3.2% [11] (Table 2). Table 2 Statistical power calculated for genotype association test in each case-control dataset with α = 0.05 Subject groups Power Detectable OR 46 cases and 204 control subjects 65% 4.435 152 cases and 111 control subjects 65% 4.400 10 cases and 178 control subjects 65% 7.975 23 cases and 89 control subjects 60% 5.