Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population

p73, a structural and functional homologue of p53, shares some p53‐like tumor suppressor activity but also possesses oncogenic activity. Therefore, p73 plays an important role in modulating cell‐cycle control and apoptosis. A potentially functional dinucleotide polymorphism, G4C14‐to‐A4T14, has been identified in the 5′ untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically form a stem‐loop structure and affect gene expression. To test the hypothesis that these 2 common variants play a role in lung cancer susceptibility, we conducted a case‐control study of 425 lung cancer patients and 588 cancer‐free controls frequency‐matched to the cases on age and sex in a Chinese population. The results showed that these 2 polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less common in the cases (0.225) than in the controls (0.287) (p = 0.0018), suggesting that this AT haplotype was protective against lung cancer. Compared to the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI: 0.26–0.80 and OR: 0.70, 95% CI: 0.53–0.92, respectively). These results suggest that this p73 dinucleotide polymorphism may have a role in lung cancer susceptibility in our study population. Further studies are needed to elucidate potential functional relevance of the p73 AT variant allele. © 2004 Wiley‐Liss, Inc.