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.

Duke Scholars

Author Qingyi Wei Population Health Sciences