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

Manenti, G; Dragani, TA

HERO ID

2216262

Reference Type

Journal Article

Year

2005

Language

English

PMID

15471897

HERO ID 2216262
In Press No
Year 2005
Title Pas1 haplotype-dependent genetic predisposition to lung tumorigenesis in rodents: a meta-analysis
Authors Manenti, G; Dragani, TA
Journal Carcinogenesis
Volume 26
Issue 5
Page Numbers 875-882
Abstract 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.
Doi 10.1093/carcin/bgh299
Pmid 15471897
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English