POLYMORPHISMS IN THE PROMOTER REGION OF THE WAF1 CIP1 GENE/

The WAF1/CIP1 gene encodes p21(waf1), a CDK inhibitor which is implica ted in cell growth arrest and differentiation, and is activated by wil d-type p53. We examined the presence of mutations in a part of the 5' flanking region which is known to contain p53 binding sites, in 50 cas es of lung cancer and 11 individuals with no history of cancer. Polymo rphisms were identified in the region close to: but not within, the p5 3 binding sites. The first polymorphism occurred at nucleotide -2203 p rior to the transcription start site, four base pairs upstream of a p5 3 binding site and created an MscI restriction site. The second polymo rphism was more complex and included four sites (nucleotides -1463, -1 526, -1533 and -1594). Two patterns (alleles) were identified for this region. These polymorphisms were observed at similar percentages in D NAs from lung cancer patients and individuals who had no history of ca ncer. A computer transcription factor motif analysis showed that these polymorphic sites are homologous (>85%) to consensus sequences of tra nscription factors such as ETS-1, Elk-l, GATA-1 and AP4 but their role in the regulation of p21(waf1) expression is still unclear. This is t he first report of polymorphisms in this region of the WAF1/CIP1 promo ter.