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Related Experiment Videos

Predisposition to lung tumorigenesis.

G Manenti1, T Nomoto, L De Gregorio

  • 1Istituto Nazionale Tumori, Via G. Venezian 1, 20133, Milan, Italy.

Toxicology Letters
|March 18, 2000
PubMed
Summary
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Mouse models reveal genetic factors influencing lung cancer susceptibility. Researchers identified human gene regions associated with lung adenocarcinoma risk and prognosis, validating the mouse model

Area of Science:

  • Genetics
  • Oncology
  • Comparative Genomics

Background:

  • Mouse inbred strains offer valuable models for studying inherited predisposition and resistance to lung cancer.
  • Previous research mapped the Pulmonary Adenoma Susceptibility 1 (Pas1) locus on mouse chromosome 6, near Kras2.
  • Identifying modifier loci is crucial for understanding the complex genetic basis of lung cancer.

Purpose of the Study:

  • To map modifier loci affecting lung cancer predisposition in mice, such as Pulmonary Adenoma Resistance 1 (Par1).
  • To investigate the association of genetic markers in the homologous human region (12p12) with lung adenocarcinoma risk and prognosis.
  • To determine if the mouse model of inherited lung tumorigenesis predicts human genetic susceptibility mechanisms.

Main Methods:

Related Experiment Videos

  • Utilized mouse crosses including susceptible Pas1(s) mice to map modifier loci like Par1, Par2, Par4, and Papg1.
  • Conducted a human association study in the Italian population, genotyping lung adenocarcinoma patients and controls.
  • Performed association studies in Japanese and European populations, analyzing KRAS2/RsaI and VNTR polymorphisms.

    • Main Results:

    • Mapped several lung tumor resistance loci (Par1, Par2, Par4) and a lung tumor progression locus (Papg1) in mice.
    • Identified borderline significant associations between specific alleles (Kras2/RsaI A2, PTHLH VNTR allele 2) and lung cancer risk in Italians.
    • Found significant associations between these alleles and tumor prognosis in Italians and a significant association of KRAS2/RsaI with prognosis in Japanese populations.

    Conclusions:

    • The mouse model of inherited lung tumorigenesis appears predictive of human genetic susceptibility mechanisms.
    • Evidence suggests the existence of a human PAS1 locus homologous to the mouse locus.
    • Genetic variations in specific regions may influence both lung adenocarcinoma risk and prognosis.