Predominant modifier of extreme liver cancer susceptibility in C57BR/cdJ female mice localized to 6 Mb on chromosome 17.

Abstract	Sex hormones influence the susceptibility of inbred mice to liver cancer. C57BR/cdJ (BR) females are extremely susceptible to spontaneous and chemically induced liver tumors, in part due to a lack of protection against hepatocarcinogenesis normally offered by ovarian hormones. BR males are also moderately susceptible, and the susceptibility of both sexes of BR mice to liver tumors induced with N,N-diethylnitrosamine relative to the resistant C57BL/6J (B6) strain is caused by two loci designated Hcf1 and Hcf2 (hepatocarcinogenesis in females) located on chromosomes 17 and 1, respectively. The Hcf1 locus on chromosome 17 is the predominant modifier of liver cancer in BR mice. To validate the existence of this locus and investigate its potential interaction with Hcf2, congenic mice for each region were generated. Homozygosity for the B6.BR(D17Mit164-D17Mit2) region resulted in a 4-fold increase in liver tumor multiplicity in females and a 4.5-fold increase in males compared with B6 controls. A series of 16 recombinants covering the entire congenic region was developed to further narrow the area containing Hcf1. Susceptible heterozygous recombinants demonstrated a 3- to 7-fold effect in females and a 1.5- to 2-fold effect in males compared with B6 siblings. The effect in susceptible lines completely recapitulated the susceptibility of heterozygous full-length chromosome 17 congenics and furthermore narrowed the location of the Hcf1 locus to a single region of the chromosome from 30.05 to 35.83 Mb.
Authors	Stephanie E-M Peychal, Andrea Bilger, Henry C Pitot, Norman R Drinkwater
Journal	Carcinogenesis (Carcinogenesis) Vol. 30 Issue 5 Pg. 879-85 (May 2009) ISSN: 1460-2180 [Electronic] England
PMID	19255062 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Estrogens Gonadal Steroid Hormones
Topics	Animals Carcinoma, Hepatocellular (genetics) Chromosome Mapping Crosses, Genetic Estrogens (physiology) Female Genetic Predisposition to Disease Gonadal Steroid Hormones (physiology) Humans Incidence Liver Neoplasms (epidemiology, genetics) Male Mice Mice, Inbred Strains Ovariectomy Polymorphism, Single Nucleotide Recombination, Genetic Sex Characteristics

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