title: Polymorphisms of p21 and p27 jointly contribute to an earlier age at diagnosis of pancreatic cancer.
abstract: p21 and p27, members of the kinase inhibitor protein (KIP) family, bind to cyclin-CDK complexes to inhibit their catalytic activity and induce cell cycle arrest. The purpose of our study was to identify whether the p21 (C-to-A), and p27 (T-to-G) polymorphisms were associated with age at diagnosis of pancreatic cancer, either independently or jointly. Two hundred and five patients with a diagnosis of pancreatic cancer were genotyped for the p21 and p27 polymorphisms. We found patients with the p21 variant genotype (CA/AA) had an earlier age at diagnosis than those with the wild-type genotype (CC) (log-rank, P=0.001; HR=1.89; 95%CI, 1.28-2.78). The p21 and p27 polymorphisms combined had a joint effect on age-associated risk for early diagnosis of pancreatic cancer (log-rank, P=0.004; HR=2.91; 95%CI, 1.49-5.67). Our findings suggest that the p21 polymorphism independently and p21 and p27 polymorphisms jointly contribute to a significantly earlier age at diagnosis of pancreatic cancer.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Jinyun
authors.initials: J
authors.lastname: Chen
authors.forename: Ann M
authors.initials: AM
authors.lastname: Killary
authors.forename: Subrata
authors.initials: S
authors.lastname: Sen
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Evans
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Frazier
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D017668:Age of Onset; D000368:Aged; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D016016:Proportional Hazards Models; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D044469:Racial Groups / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; C114476:PSMD9 protein, human; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen; D046988:Proteasome Endopeptidase Complex