DOI QR코드

DOI QR Code

P53 Arg72Pro and MDM2 SNP309 Polymorphisms Cooperate to Increase Lung Adenocarcinoma Risk in Chinese Female Non-smokers: A Case Control Study

  • Ren, Yang-Wu (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Yin, Zhi-Hua (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Wan, Yan (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Guan, Peng (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Wu, Wei (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Li, Xue-Lian (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Zhou, Bao-Sen (Department of Epidemiology, School of Public Health, China Medical University)
  • Published : 2013.09.30

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.

Keywords

References

  1. Ara S, Lee PS, Hansen MF, et al (1990). Codon 72 polymorphism of the Tp53 gene. Nucleic acids research, 18, 4961.
  2. Bond GL, Hu W, Bond EE, et al (2004). A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell, 119, 591-602. https://doi.org/10.1016/j.cell.2004.11.022
  3. Bond GL, Hu W,Levine A (2005). A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res, 65, 5481-4. https://doi.org/10.1158/0008-5472.CAN-05-0825
  4. Brennan P (2002). Gene-environment interaction and aetiology of cancer: what does it mean and how can we measure it? Carcinogenesis, 23, 381-7. https://doi.org/10.1093/carcin/23.3.381
  5. Caceres DD, Quinones LA, Schroeder JC, et al (2009). Association between p53 codon 72 genetic polymorphism and tobacco use and lung cancer risk. Lung, 187, 110-5. https://doi.org/10.1007/s00408-008-9133-3
  6. Chene P (2003). Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer, 3, 102-9. https://doi.org/10.1038/nrc991
  7. Chua HW, Ng D, Choo S, et al (2010). Effect of MDM2 SNP309 and p53 codon 72 polymorphisms on lung cancer risk and survival among non-smoking Chinese women in Singapore. BMC Cancer, 10, 88. https://doi.org/10.1186/1471-2407-10-88
  8. Dulic V, Kaufmann WK, Wilson SJ, et al (1994). p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell, 76, 1013-23. https://doi.org/10.1016/0092-8674(94)90379-4
  9. Dumont P, Leu JI, Della Pietra AC, et al (2003). The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet, 33, 357-65. https://doi.org/10.1038/ng1093
  10. Duong V, Boulle N, Daujat S, et al (2007). Differential regulation of estrogen receptor alpha turnover and transactivation by Mdm2 and stress-inducing agents. Cancer Res, 67, 5513-21. https://doi.org/10.1158/0008-5472.CAN-07-0967
  11. Eymin B, Gazzeri S, Brambilla C, et al (2002). Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors. Oncogene, 21, 2750-61. https://doi.org/10.1038/sj.onc.1205359
  12. Haupt Y, Maya R, Kazaz A, et al (1997). Mdm2 promotes the rapid degradation of p53. Nature, 387, 296-9. https://doi.org/10.1038/387296a0
  13. Hu Z, Ma H, Lu D, et al (2006). Genetic variants in the MDM2 promoter and lung cancer risk in a Chinese population. International journal of cancer. Int J Cancer, 118, 1275-8. https://doi.org/10.1002/ijc.21463
  14. Jassem J, Szymanowska A, Jassem E, et al (2005). Relation between p53 codon 72 polymorphism and somatic p53 gene mutation in non-small cell lung cancer (NSCLC). Ejc Supplements, 3, 336-.
  15. Jemal A, Bray F,Center MM (2011). Global Cancer Statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  16. Jin S, Levine AJ (2001). The p53 functional circuit. J Cell Sci, 114, 4139-40.
  17. Karlsson C, Helenius G, Fernandes O, et al (2012). Oestrogen receptor beta in NSCLC - prevalence, proliferative influence, prognostic impact and smoking. APMIS, 120, 451-8. https://doi.org/10.1111/j.1600-0463.2011.02850.x
  18. Kastan MB, Onyekwere O, Sidransky D, et al (1991). Participation of p53 protein in the cellular response to DNA damage. Cancer Res, 51, 6304-11.
  19. Lain S,Lane D (2003). Improving cancer therapy by nongenotoxic activation of p53. Eur J Cancer, 39, 1053-60. https://doi.org/10.1016/S0959-8049(03)00063-7
  20. Li M, Yin Z, Guan P, et al (2008). XRCC1 polymorphisms, cooking oil fume and lung cancer in Chinese women nonsmokers. Lung Cancer, 62, 145-51. https://doi.org/10.1016/j.lungcan.2008.03.002
  21. Li Y, Qiu LX, Shen XK, et al (2009). A meta-analysis of Tp53 codon 72 polymorphism and lung cancer risk: evidence from 15,857 subjects. Lung Cancer, 66, 15-21. https://doi.org/10.1016/j.lungcan.2008.12.009
  22. Lind H, Zienolddiny S, Ekstrom PO, et al (2006). Association of a functional polymorphism in the promoter of the MDM2 gene with risk of nonsmall cell lung cancer. International journal of cancer. Int J Cancer, 119, 718-21. https://doi.org/10.1002/ijc.21872
  23. Liu D, Wang F, Guo X, et al (2013). Association between p53 codon 72 genetic polymorphisms and tobacco use and lung cancer risk in a Chinese population. Mol Biol Rep, 40, 645-9. https://doi.org/10.1007/s11033-012-2103-0
  24. Momand J, Zambetti GP, Olson DC, et al (1992). The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69, 1237-45. https://doi.org/10.1016/0092-8674(92)90644-R
  25. Mooney LA, Santella RM, Covey L, et al (1995). Decline of DNA damage and other biomarkers in peripheral blood following smoking cessation. Cancer Epidemiol Biomarkers Prev, 4, 627-34.
  26. Pesch B, Kendzia B, Gustavsson P, et al (2012). Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of casecontrol studies. Int J Cancer, 131, 1210-9. https://doi.org/10.1002/ijc.27339
  27. Piao JM, Kim HN, Song HR, et al (2011). p53 codon 72 polymorphism and the risk of lung cancer in a Korean population. Lung Cancer, 73, 264-7. https://doi.org/10.1016/j.lungcan.2010.12.017
  28. Sakiyama T, Kohno T, Mimaki S, et al (2005). Association of amino acid substitution polymorphisms in DNA repair genes Tp53, POLI, REV1 and LIG4 with lung cancer risk. Int J Cancer, 114, 730-7. https://doi.org/10.1002/ijc.20790
  29. Siegfried JM (2010). Early changes in pulmonary gene expression following tobacco exposure shed light on the role of estrogen metabolism in lung carcinogenesis. Cancer Prev Res (Phila), 3, 692-5. https://doi.org/10.1158/1940-6207.CAPR-10-0093
  30. Smyth JF (1996). Cancer genetics and cell and molecular biology. Is this the way forward? Chest, 109, 125S-9S. https://doi.org/10.1378/chest.109.5_Supplement.125S
  31. Thomas M, Kalita A, Labrecque S, et al (1999). Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol, 19, 1092-100. https://doi.org/10.1128/MCB.19.2.1092
  32. Tokiwa H, Sera N, Nakashima A, et al (1994). Mutagenic and carcinogenic significance and the possible induction of lung cancer by nitro aromatic hydrocarbons in particulate pollutants. Environ Health Perspect, 102, 107-10. https://doi.org/10.1289/ehp.94102s10107
  33. Wu X, Zhao H, Amos CI, et al (2002). p53 genotypes and haplotypes associated with lung cancer susceptibility and ethnicity. J Natl Cancer Inst, 94, 681-90. https://doi.org/10.1093/jnci/94.9.681
  34. Yin Z, Su M, Li X, et al (2009). ERCC2, ERCC1 polymorphisms and haplotypes, cooking oil fume and lung adenocarcinoma risk in Chinese non-smoking females. J Exp Clin Cancer Res, 28, 153. https://doi.org/10.1186/1756-9966-28-153
  35. Zang EA,Wynder EL (1996). Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst, 88, 183-92. https://doi.org/10.1093/jnci/88.3-4.183
  36. Zhang H, Wang G,Tan W (2002). [Study on the effects of cooking oil fume condensate on the DNA integrity]. Wei Sheng Yan Jiu, 31, 238-40.
  37. Zhang X, Miao X, Guo Y, et al (2006). Genetic polymorphisms in cell cycle regulatory genes MDM2 and Tp53 are associated with susceptibility to lung cancer. Human mutation, 27, 110-7. https://doi.org/10.1002/humu.20277
  38. Zhuo W, Zhang L, Zhu B, et al (2012). Association of MDM2 SNP309 variation with lung cancer risk: evidence from 7196 cases and 8456 controls. PLoS One, 7, e41546. https://doi.org/10.1371/journal.pone.0041546

Cited by

  1. Distribution of EGFR Mutations Commonly Observed in Primary Lung Adenocarcinomas in Pakistan as Predictors for Targeted Therapy vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7125
  2. Effects of p53 Codon 72 and MDM2 SNP309 Polymorphisms on Gastric Cancer Risk among the Iranian Population vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7413
  3. Analysis of TP53 Polymorphisms in North Indian Sporadic Esophageal Cancer Patients vol.15, pp.19, 2014, https://doi.org/10.7314/APJCP.2014.15.19.8413
  4. MicroRNA-146a rs2910164 polymorphism is associated with susceptibility to non-small cell lung cancer in the Chinese population vol.31, pp.10, 2014, https://doi.org/10.1007/s12032-014-0194-2
  5. Association of a p53 Codon 72 Gene Polymorphism with Environmental Factors and Risk of Lung Cancer: a Case Control Study in Mizoram and Manipur, a High Incidence Region in North East India vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10653
  6. P53 Polymorphism at Codon 72 is Associated with Keratocystic Odontogenic Tumors in the Thai Population vol.16, pp.5, 2015, https://doi.org/10.7314/APJCP.2015.16.5.1997
  7. MDM2 (RS769412) G>A Polymorphism in Cigarette Smokers: a Clue for the Susceptibility to Smoking and Lung Cancer Risk vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.4057
  8. Genetic association of single nucleotide polymorphisms in P53 pathway with gastric cancer risk in a Chinese Han population vol.32, pp.1, 2015, https://doi.org/10.1007/s12032-014-0401-1
  9. Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk vol.2, pp.5, 2014, https://doi.org/10.3892/br.2014.305