title: P53 Arg72Pro and MDM2 SNP309 polymorphisms cooperate to increase lung adenocarcinoma risk in Chinese female non-smokers: a case control study.
abstract: BACKGROUND
  Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer.
  
  
  METHODS
  We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non- smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay.
  
  
  RESULTS
  The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles.
  
  
  CONCLUSIONS
  P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110001, PR China E-mail : bszhou@mail.cmu.edu.cn.
authors.forename: Yang-Wu
authors.initials: YW
authors.lastname: Ren
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Yin
authors.forename: Yan
authors.initials: Y
authors.lastname: Wan
authors.forename: Peng
authors.initials: P
authors.lastname: Guan
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Li
authors.forename: Bao-Sen
authors.initials: BS
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2