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Published on: March 30, 2019

Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer

Xuemei Zhang1, Xiaoping Miao, Yongli Guo

  • 1Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Human Mutation
|November 16, 2005
PubMed

Insights

Genetic variations in MDM2 and TP53 genes increase lung cancer risk, especially in smokers with specific genotypes. These findings highlight the role of cell cycle regulatory genes in cancer development.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The tumor suppressor TP53 pathway is vital for preventing cancer by inducing cell cycle arrest and apoptosis.
  • MDM2 acts as a key negative regulator of the TP53 pathway and is often overexpressed in cancers.
  • Genetic variations in MDM2 and TP53 may influence individual susceptibility to lung cancer.

Purpose of the Study:

  • To investigate the association between genetic variations in the MDM2 promoter and TP53 coding regions and the risk of developing lung cancer.
  • To explore potential gene-gene interactions between MDM2 and TP53 polymorphisms and their combined effect on lung cancer risk.
  • To examine the interaction between these genetic polymorphisms, smoking, and lung cancer risk.

Main Methods:

  • Genotyping of MDM2 (c.-5+309G>T) and TP53 (c.215G>C, Arg72Pro) polymorphisms using tetra-primer ARMS-PCR or PCR-RFLP.
  • Analysis of genotype data from 1,106 lung cancer patients and 1,420 controls.
  • Logistic regression analysis to estimate odds ratios (OR) and confidence intervals (CI) for lung cancer risk, including gene-gene and gene-environment interactions.

Main Results:

  • Increased lung cancer risk was associated with MDM2 GG (OR=1.83) and TG (OR=1.33) genotypes.
  • The TP53 Pro/Pro genotype was linked to a higher risk of lung cancer (OR=1.47) compared to Arg/Arg.
  • A supermultiplicative increase in lung cancer risk was observed with the combined MDM2 GG and TP53 Pro/Pro genotypes (OR=4.56).
  • Significant interactions were found between these polymorphisms and smoking, with the highest risk observed in smokers carrying both MDM2 GG and TP53 Pro/Pro genotypes (OR=10.41).

Conclusions:

  • Genetic polymorphisms in MDM2 and TP53 contribute to lung cancer susceptibility.
  • The combined effect of specific MDM2 and TP53 genotypes significantly elevates lung cancer risk.
  • Interactions between these genetic factors and smoking represent a critical determinant of lung cancer development.

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