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

Abstract

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.

Association of p73 G4C14-to-A4T14 polymorphism with non-small cell lung cancer risk

“…Two previous studies observed that the AT allele was associated with a significantly increased incidence of lung cancer compared with the GC/GC allele in a Northern Chinese population (10) and a non-Hispanic Caucasian population (16). By contrast, one study reported a marked association between the AT allele and the decreased risk of developing lung cancer in a Chinese population (15), which is consistent with the results of the present study. However, a Table II.…”

“…However, the results of previous studies regarding the association between p73 G4C14-to-A4T14 polymorphism and susceptibility to lung cancer are inconsistent (10,(15)(16)(17)(18). Two previous studies observed that the AT allele was associated with a significantly increased incidence of lung cancer compared with the GC/GC allele in a Northern Chinese population (10) and a non-Hispanic Caucasian population (16).…”

“…Li et al (13) revealed Association of p73 G4C14-to-A4T14 polymorphism with non-small cell lung cancer risk a marked association in an American population between the AT allele or genotype and the risk of developing squamous cell carcinoma of the head and neck (13); in addition, a study by Ryan et al (14) indicated that AT/AT homozygotes were significantly uncommon in esophageal cancer patients from an Irish population. Furthermore, Hu et al (15) reported an association between dinucleotide polymorphism of the p73 gene and a reduced risk of lung cancer in a Chinese population and Li et al (16) determined that the variant GC/AT and AT/AT genotypes were associated with a significantly increased risk of lung cancer (16). Associations between p73 gene polymorphisms and the risk of lung cancer therefore illustrate that the p73 gene has a critical role in lung cancer carcinogenesis (15)(16)(17)(18).…”

“…Furthermore, Hu et al (15) reported an association between dinucleotide polymorphism of the p73 gene and a reduced risk of lung cancer in a Chinese population and Li et al (16) determined that the variant GC/AT and AT/AT genotypes were associated with a significantly increased risk of lung cancer (16). Associations between p73 gene polymorphisms and the risk of lung cancer therefore illustrate that the p73 gene has a critical role in lung cancer carcinogenesis (15)(16)(17)(18). However, there have been inconsistencies in the data regarding these associations.…”

Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

“…The role of the p73 G4C14A4T14 polymorphism in the risk of developing cancer has been investigated in several studies [9][10][11][12][13][14][15][16][17], but the results are inconsistent, varying between types of cancers and populations. It has previously been found that the AT/AT genotype may be associated with a higher risk of developing colorectal cancer, but also that patients carrying the AT allele has a better prognosis [18].…”