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Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern

Rongrong Yang1, Lei Yang, Fuman Qiu

  • 1The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.

Plos One
|November 9, 2013
PubMed

Insights

Genetic variations in Protein Phosphatase-2A (PP2A) genes, specifically PPP2R1A and PPP2R5E, are linked to increased lung cancer risk in Chinese populations. These findings suggest potential biomarkers for predicting lung cancer susceptibility.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Protein phosphatase-2A (PP2A) is a key tumor suppressor involved in regulating oncogenic kinases.
  • Reduced PP2A expression is observed during lung carcinogenesis, suggesting a role in cancer development.
  • Single nucleotide polymorphisms (SNPs) in PP2A subunit genes may influence PP2A function and lung cancer susceptibility.

Purpose of the Study:

  • To investigate the association between functional SNPs in major PP2A subunit genes and lung cancer risk in a Chinese population.
  • To identify specific genetic variants that may contribute to lung cancer susceptibility.

Main Methods:

  • A two-stage case-control study involving 1559 lung cancer patients and 1679 controls of Chinese ethnicity.
  • Genotyping of eight putative functional SNPs and one identified functional SNP (rs11453459) in seven PP2A subunit genes (PPP2R1A, PPP2R1B, PPP2CA, PPP2R2A, PPP2R2B, PPP2R5C, PPP2R5E).
  • Statistical analysis to assess the association between genotypes and lung cancer risk, including combined variant analysis and functional assays.

Main Results:

  • The rs11453459 variant genotypes (G/-G/GG) in PPP2R1A and the rs1255722AA variant genotype in PPP2R5E were associated with increased lung cancer risk (OR=1.31, 95% CI=1.13-1.51 and OR=1.27, 95% CI=1.07-1.51, respectively).
  • A combined analysis of these two variants showed a positive, dose-response association with lung cancer risk (P trend = 5.63 × 10(-6)).
  • Lung cancer tissues with the rs1255722AA genotype exhibited significantly lower PPP2R5E mRNA levels compared to those with GG/GA genotypes, indicating a functional impact.

Conclusions:

  • Two functional variants in PPP2R1A and PPP2R5E, and their combination, are significantly associated with lung cancer risk in the Chinese population.
  • These genetic variants may serve as valuable biomarkers for predicting lung cancer risk.
  • Further research is warranted to elucidate the precise mechanisms by which these SNPs influence lung cancer development.

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