Map Making in the 21st Century: Charting Breast Cancer Susceptibility Pathways in Rodent Models

Article

Abstract

Genetic factors play an important role in determining risk and resistance to increased breast cancer. Recent technological advances have made it possible to analyze hundreds of thousands of single nucleotide polymorphisms in large-scale association studies in humans and have resulted in identification of alleles in over 20 genes that influence breast cancer risk. Despite these advances, the challenge remains in identifying what the functional polymorphisms are that confer the increased risk, and how these genetic variants interact with each other and with environmental factors. In rodents, the incidence of mammary tumors varies among strains, such that they can provide alternate ideas for candidate pathways involved in humans. Mapping studies in animals have unearthed numerous loci for breast cancer susceptibility that have been validated in human populations. In a reciprocal manner, knockin and knockout mice have been used to validate the tumorigenicity of risk alleles found in population studies. Rodent studies also underscore the complexity of interactions among alleles. The fact that genes affecting risk and resistance to mammary tumors in rodents depend greatly upon the carcinogenic challenge emphasizes the importance of gene x environment interactions. The challenge to rodent geneticists now is to capitalize on the ability to control the genetics and environment in rodent models of tumorigenesis to better understand the biology of breast cancer development, to identify those polymorphisms most relevant to human susceptibility and to identify compensatory pathways that can be targeted for improved prevention in women at highest risk of developing breast cancer.

Keywords

Breast cancer Animal models Genetic mapping Modifier genes p53 

Abbreviations

GWAS

Genome-wide association studies

LFS

Li-Fraumeni Syndrome

CGEMS

Cancer Genetics Markers of Susceptibility

SNP

Single nucleotide polymorphism

DMBA

Dimethyl-α-benzanthracene

QTL

Quantitative trait locus

Notes

Financial and Material Support

The research was supported by funds from Avon Foundation (DJJ), National Institutes of Health (R01-CA105452, R01-ES015739, DJJ), Department of Defense (W81XWH-10-1-0637, DJJ), National Health and Medical Research Council, Australia (ACB) and National Breast Cancer Foundation, Australia (ACB).

Conflict of Interest

The authors have no competing interests.

Permissions

None.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia
  2. 2.Pioneer Valley Life Sciences InstituteSpringfieldUSA
  3. 3.Department of Veterinary & Animal SciencesUniversity of Massachusetts AmherstAmherstUSA

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