Pas1 haplotype-dependent genetic predisposition to lung tumorigenesis in rodents: a meta-analysis

Rodent species and strains show wide variations in susceptibility to lung tumorigenesis. In mice, hierarchical clustering of 29 inbred laboratory strains by pulmonary adenoma susceptibility 1 (Pas1) locus polymorphisms separated the strains into either an A/J- or a C57BL/6J-type Pas1 haplotype. A po...

Full description

Saved in:
Bibliographic Details
Published in:Carcinogenesis (New York) 2005-05, Vol.26 (5), p.875-882
Main Authors: Manenti, Giacomo, Dragani, Tommaso A.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - pharmacology
confidence interval
Cricetinae
Genetic Predisposition to Disease
Haplotypes
Humans
Lung Neoplasms - chemically induced
Lung Neoplasms - genetics
Medical sciences
Mice
Mice, Inbred Strains
Neoplasms, Experimental - chemically induced
Neoplasms, Experimental - genetics
odds ratio
Pas1
Phenotype
pulmonary adenoma susceptibility 1
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Rodent species and strains show wide variations in susceptibility to lung tumorigenesis. In mice, hierarchical clustering of 29 inbred laboratory strains by pulmonary adenoma susceptibility 1 (Pas1) locus polymorphisms separated the strains into either an A/J- or a C57BL/6J-type Pas1 haplotype. A pooled analysis (including >8500 mice) of studies on spontaneous and chemically induced lung tumorigenesis in these strains revealed a significantly higher risk of spontaneous lung tumors [odds ratio (OR) 12.17; 95% confidence interval (CI) 9.00–16.45] as well as of chemically induced lung tumors (OR 15.14; 95% CI 12.51–18.31) in the A/J-type haplotype. Strain differences were observed with six different carcinogens, suggesting that Pas1 locus activity is carcinogen-independent. Thus, the present meta-analysis indicates a link between the genetic control of spontaneous and chemically induced lung tumor susceptibility in mice. The Pas1 susceptibility allele is frequent in the population of inbred mouse strains, whereas a counterpart appears to be absent or rare in rat and hamster strains. These findings might help in the interpretation of results of rodent carcinogenicity bioassays and assessing the risk of lung carcinogenesis from chemicals.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgh299