title: Association between the p73 G4C14-to-A4T14 polymorphism and risk of nasopharyngeal carcinoma: a case-control and family-based study.
abstract: p73, a structural and functional homolog of p53, plays an important role in modulating cell cycle control and apoptosis. We examined whether the p73 G4C14-to-A4T14 polymorphism was related to the risk of nasopharyngeal carcinoma (NPC) among Chinese populations. The G4C14-to-A4T14 polymorphism was genotyped in 593 NPC cases and 480 controls, and in 102 NPC trios. Logistic regression analysis and transmission/disequilibrium tests (TDT) were performed to evaluate whether there was an association between the polymorphism and NPC, respectively. Functional analyses were conducted to verify the biological relevance of the polymorphism. We observed that compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly increased susceptibility to NPC [odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.16-1.95; P = 0.002]. Furthermore, compared with the GC/GC genotype, the GC/AT + AT/AT genotypes were significantly associated with the advanced lymph node metastasis (OR = 1.47; 95% CI = 1.02-2.11; P = 0.041). A significantly greater than expected transmission of the AT allele from heterozygous parents to offspring was also observed (P = 0.049) using the TDT. By using the TdT-mediated dUPT-biotin nick end labeling assay, we observed lower apoptosis in NPC tissues from the AT allele carriers compared with that from non-carriers. Furthermore, the relative TAp73 RNA levels of the AT allele were lower than those of the GC allele in heterozygous cells. Our findings suggest that the p73 G4C14-to-A4T14 polymorphism may play a role in mediating the susceptibility to NPC in Chinese populations.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, People's Republic of China and.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Institute of Guangxi, Nanning 530021, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Peiyao
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Lixa
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China, zhougq114@gmail.com hefc@nic.bmi.ac.cn.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China, zhougq114@gmail.com.
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000328:Adult; D017209:Apoptosis; D002277:Carcinoma; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins