Polymorphisms of p21 and p27 jointly contribute to an earlier age at diagnosis of pancreatic cancer

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.