title: A novel tri-allelic insertion/deletion polymorphism in the promoter of p21(Waf1/Cip1) and the association with gastric cancer.
abstract: OBJECTIVE
  p21(Waf1/Cip1) is a cyclin-dependent kinase inhibitor that is pivotal in arresting cellular growth in terminal cell differentiation and apoptosis. Thus, the existence of natural variants of p21(Waf1/Cip1) could be linked to specific cancer. The purpose of this report was to identify a novel tri-allelic insertion/deletion (INDEL) polymorphism (rs4135235) involving a poly-T sequence in the promoter region of p21(Waf1/Cip1) gene and to explore its role in gastric cancer (GC).
  
  
  METHODS
  A total of unrelated 676 subjects (376 GC patients; 300 cancer-free controls) were enrolled in the study, and genomic DNA was obtained from each subject for genotyping. PCR-directed sequencing technique was used to detect the genotypes of the polymorphism. TA cloning was used to confirm the existence of three alleles. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis.
  
  
  RESULTS
  Six genotypes (9T/9T, 10T/10T, 11T/11T, 9T/10T, 10T/11T, and 9T/11T) and three alleles (9Ts, 10Ts, and 11Ts) were identified among all study subjects. GC cases were different from the control group with over-representation of 9T/11T heterozygotes (19.7% vs. 12.3%) and under-representation of 10T/10T homozygotes (18.4% vs. 20.7%). Compared with those carrying 10T/10T, individuals with 9T/11T increased the susceptibility for GC (OR=1.797, 95%CI=1.065-3.031).
  
  
  CONCLUSIONS
  Our findings confirmed the existence of a tri-allelic polymorphism in the promoter of p21(Waf1/Cip1). It has also shown the heterozygous genotype 9T/11T to be a potential risk factor for GC in the Chinese population.
authors.affiliation: 1 Key Laboratory of Reproduction and Heredity, Oncology Department of Cancer Hospital, General Hospital, Ningxia Medical University , Yinchuan, People's Republic of China .
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.forename: Ningju
authors.initials: N
authors.lastname: Wang
authors.forename: Hanmei
authors.initials: H
authors.lastname: Liang
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ye
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: He
authors.forename: Yideng
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yang
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21