Association between the p73 exon 2 G4C14-to-A4T14 polymorphism and cancer risk: a meta-analysis.
The TP53 homolog p73 is structurally and functionally similar to TP53 and plays an important role in modulating cell-cycle control, apoptosis, and cell growth. G4C14-to-A4T14 is the most commonly studied polymorphism of this gene for its association with risk of cancers, but the results are confusing rather than conclusive. We performed a meta-analysis using 21 eligible studies with a total of 7581 patients and 10,413 controls to summarize the data for an association between the p73 G4C14-to-A4T14 polymorphism and cancer risk. Compared with the common GC/GC genotype, the AT carriers (AT/GC, AT/AT) had a 1.18-fold elevated risk of cancer (95% confidence interval [CI]=1.11-1.25, p<0.00001) in a dominant genetic model as estimated in a fixed effect model. The effect of the G4C14-to-A4T14 polymorphism was further evaluated through stratification analysis. In four lung cancer studies, the variant genotypes had a significantly increased risk of lung cancer (odds ratio [OR]=1.16, 95% CI=1.04-1.28, p=0.005). Similar phenomena were also found in two squamous cell carcinoma of the head and neck studies (OR=1.32, 95% CI=1.12-1.56, p=0.0010), two oral cancer studies (OR=1.57, 95% CI=1.26-1.95, p<0.0001), and three colorectal cancer studies (OR=1.23, 95% CI=1.01-1.50, p=0.04). Increased risk of cancer associated with G4C14-to-A4T14 variant genotypes was pronounced in Caucasians (OR=1.21, 95% CI=1.11-1.31, p<0.00001), the Japanese population (OR=1.24, 95% CI=1.01-1.52, p=0.04), and the Korean population (OR=1.27, 95% CI=1.07-1.52, p=0.007). Our meta-analysis suggests that the p73 G4C14-to-A4T14 polymorphism genotypes (GC/AT+AT/AT) may be associated with an increased risk of cancer in most cancer types and ethnicities.
Department of Oncology, Chinese PLA General Hospital, Beijing, China.
Yi
Y
Hu
Lan
L
Jiang
Jian
J
Zheng
Yonghe
Y
You
Yifeng
Y
Zhou
Shunchang
S
Jiao
D020856:AT Rich Sequence / Q000235:genetics; D000465:Algorithms; D001482:Base Composition / Q000235:genetics; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020862:GC Rich Sequence / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods / Q000706:statistics & numerical data*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology*; D012196:Review Literature as Topic; D012307:Risk Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins