title: Genetic polymorphisms in cell cycle regulatory genes CCND1 and CDK4 are associated with susceptibility to breast cancer.
abstract: OBJECTIVE
  This study was performed to screen cyclin D1 (CCND1) and cyclin dependent kinases (CDK4) genes in order to evaluate their association with breast carcinogenesis.
  
  
  METHODS
  The germline screening of these genes was carried out by combining polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP), followed by DNA sequence analysis. A total of 400 individuals (200 breast cancer patients and 200 healthy controls) were recruited prospectively for this study.
  
  
  RESULTS
  Sequence analyses of the coding region of CCND1 revealed 12 mutations. When analyzed, a significant association was found between CCND1 mutations and breast cancer. It was observed that a 6-fold increased breast cancer risk (odds ratio/OR=5.75, 95% confidence interval/CI=1.26-26.33) was associated with Cys7Tyr in breast cancer patients when compared with healthy controls. In addition, a 5-fold increased breast cancer risk was associated with Trp63Stop mutation (OR=5.44, 95% CI=1.82-16.23), 10861C>A (OR=4.84; 95% CI=1.60-14.58) and 7720insTT (OR=5.32, 95% CI=1.98-14.23) in breast cancer patients compared to healthy controls. Concerning CDK4 gene, 5 mutations were identified and a significant association was observed between CDK4 gene mutations and breast cancer. It was observed that a 6-fold increased risk of breast cancer (OR=5.71, 95% CI=0.29-4.65) was associated with 5693 T>A. In addition, a 5-fold increased risk of breast cancer (OR=5.05, 95% CI=2.17-11.78) was associated with 5732 G>A in breast cancer patients compared to controls.
  
  
  CONCLUSIONS
  In this study, our results showed that CCND1 and CDK4 mutations are associated with an increased risk of breast cancer, and may serve as biomarkers for early diagnosis and detection of breast cancer.
authors.affiliation: Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Abid
authors.initials: A
authors.lastname: Ullah Shah
authors.forename: Ishrat
authors.initials: I
authors.lastname: Mahjabeen
authors.forename: Mahmood Akhtar
authors.initials: MA
authors.lastname: Kayani
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4