Background: As the main downstream effecter of tumor suppressor p53, p21(Waf1/Cip1) functions as a unique link from p53 to cell-cycle arrest and DNA repair. In contrast to p53, p21(Waf1/Cip1) has general rare mutations. The natural genetic variants of p21(Waf1/Cip1) have thus emerged for study to enhance understanding of interindividual differences in cancer risk. Two polymorphisms in the p21 ( Waf1/Cip1 ) gene, i.e., codon 31 in the coding region and IVS2+16 in intron 2, have been identified and appeared to influence the expression of p21(Waf1/Cip1). The aim of this study is to investigate the potential association of the above two variants, including one new single-nucleotide polymorphism (SNP) 309 in the promoter region of p21 ( Waf1/Cip1 ), with susceptibility to esophageal cancer (EC).

Patients and methods: The study involved 80 cancer patients and 200 cancer-free controls from Ningxia Region of China. Three variations (codon 31, IVS2+16, and SNP 309) were identified by polymerase chain reaction (PCR) direct sequencing method, and associations of each individual SNP and haplotypes of the three SNPs with esophageal cancer were analyzed.

Results: The correlation results supported that codon 31 Ser homozygosity conferred risk for the process of developing EC [odds ratio (OR) = 2.542, 95% confidence interval (CI) = 1.347-4.730]. In the combined study of the three variations, HapA and HapB appeared to influence the risk of EC.

Conclusions: Our findings indicated that codon 31 Ser allele homozygosity, either alone or in combination with the other two SNPs, may be associated with development of EC. These findings warrant validation in a larger study of EC patients.