TY - JOUR T1 - Gene polymorphisms of p53 at codon 72 and MDM2 SNP309 are associated with lung cancer risk and emphysematous changes in smokers JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P819 AU - Shiro Mizuno AU - Makoto Kobayashi AU - Taku Oikawa AU - Ken Nakagawa AU - Kazuhiro Osanai AU - Maiko Kadowaki AU - Takeshi Ishizaki AU - Hirohisa Toga Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P819.abstract N2 - Rationale: In lung tissues from COPD patients, the expression of p53 is increased and the p53 expression is mainly regulated by MDM2. Gene polymorphism of p53 at codon 72 is known to affect the transcriptional activation of apoptotic effector proteins, and gene polymorphism of MDM2 SNP309 is known to change the affinity of the Sp1 transcription factor, which leads to increased expression of MDM2.Methods: 323 patients who have a smoking history were included in this study. 91 blood samples were from patients with normal lung function, the remainder of the samples were from patients with mild (n=67; GOLD I), moderate (n=103; GOLD II) and severe COPD (n=62; GOLD III and IV). 29 blood samples were from patients with lung cancer. Polymorphisms of p53 at codon 72 and MDM2 SNP309 genes were analyzed using PCR-RFLP technique on genomic DNA. Analysis of chest HRCT images for emphysematous changes (%LAA) was performed using computer software (LungVison ver 2.1, Cybernet Systems CO. LTD.).Results: The %LAA was significantly greater in the patients with a G/G genotype for p53 at codon 72 and T/T genotypes for MDM2 SNP309 compared with C/C genotype for p53 and G/G genotypes for MDM2. The proportion of the p53 and MDM2 genotype among lung cancer were significantly different compared to the patients without lung cancer.Conclusion: These data indicate that the polymorphisms of p53 and MDM2, which may affect apoptosis signaling of the lung cells, are associated with smoking-related emphysematous changes and tumor suppressor mechanisms of lung cancer. ER -