Abstract
Studies of cancer predisposition have largely concentrated on the role of high-penetrance susceptibility genes. Less than 10% of the total human tumor burden, however, is accounted for by mutations in these genes. More genetic variation in cancer risk is likely to be due to commoner but lower penetrance alleles. In man, such modifier genes will be difficult to find since they do not segregate as single Mendelian traits. The mouse offers a powerful system for studying polygenic traits such as cancer and has been widely used for this purpose. Novel approaches that might accelerate the identification of these low-penetrance cancer susceptibility genes by using mouse models will be discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Balmain A (2002) Cancer as a complex genetic trait: tumor susceptibility in humans and mouse models. Cell 108:145–152
Balmain A, Harris CC (2000) Carcinogenesis in mouse and human cells: parallels and paradoxes. Carcinogenesis 21:371–377
Balmain A, Nagase H (1998) Cancer resistance genes in mice: models for the study of tumour modifiers. Trends Genet 14:139–144
Cavanee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–784
Dunning AM, Healey CS, Pharaoh PDP, Teare MD, Ponder BAJ, Easton DF (1999) A systemic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 8:843–854
Ewart-Toland A, de Koning JP, Dunning AM, Mao JH, Pharaoh PDP, Nagase H, Burns J, West S, Mannermaa A, Kataja V, Easton DF, Ponder BAJ, Balmain A (2002) Identification of STK6 (Aurora2) as a modifier of cancer risk in mouse and man (submitted)
Fijneman RJ, de Vries SS, Jansen RC, Demant P (1996) Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse. Nat Genet 14:465–467
Fijneman RJ, Jansen R, van der Valk M, Demant P (1998) High frequency of interactions between lung cancer susceptibility genes in the mouse: mapping of Sluc5 to Sluc14. Cancer Res 58:4794–4798
Fodor FH, Weston A, Bleiweiss IJ, McCurdy LD, Walsh MM, Tartter PI, Brower ST, Eng CM (1998) Frequency and carrier risk associated with common BRCAI and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 63:45–54
Hann B, Balmain A (2001) Building “validated” mouse models of human cancer. Curr Opin Cell Biol 13:778–784
Legare ME, Bartlett FS, Frankel WN (2000) A major effect QTL determined by multiple genes in epileptic EL mice. Genome Res 10:42–48
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000) Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85
Macleod KF, Jacks T (1999) Insights into cancer from transgenic mouse models. J Pathol 187:43–60
Mott R, Talbot CJ, Turri MG, Collins AC, Flint J (2000) A method for fine mapping quantitative trait loci in outbred animal stocks. Proc Natl Acad Sci USA 97:12649–12654
Nagase H, Bryson S, Cordell H, Kemp CJ, Fee F, Balmain A (1995) Distinct genetic loci control development of benign and malignant skin tumours in mice. Nat Genet 10:424–429
Nagase H, Mao JH, Balmain A (1999) A subset of skin tumor modifier loci determines survival time of tumor-bearing mice. Proc Natl Acad Sci USA 96:15032–15037
Nagase H, Mao JH, de Koning JP, Minami T, Balmain A (2001) Epistatic interactions between skin tumor modifier loci in interspecific (spretus/musculus) backcross mice. Cancer Res 61:1305–1308
Nathanson KN, Wooster R, Weber BL (2001) Breast cancer genetics: what we know and what we need. Nat Med 7:552–556
Perera FP, Weinstein IB (2000) Molecular epidemiology: recent advances and future directions. Carcinogenesis 21:517–524
Peto J, Houlston RS (2001) Genetics and the common cancers. Eur J Cancer 37:S88–S96
Ponder BAJ (2001) Cancer genetics. Nature 411:336–341
The International SNP Map Working Group (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–933
Tripodis N, Hart AAM, Fijneman RJA, Demant P (2001) Complexity of lung cancer modifiers: mapping of thirty genes and twenty-five interactions in half of the mouse genome. J Natl Cancer Inst 93:1484–1491
van Wezel T, Stassen AP, Moen CJ, Hart AA, van der Valk MA, Demant P (1996) Gene interaction and single gene effects in colon tumour susceptibility in mice. Nat Genet 14:468–470
van Wezel T, Ruivenkamp CA, Stassen AP, Moen CJ, Demant P (1999) Four new colon cancer susceptibility loci, Scc6 to Scc9 in the mouse. Cancer Res 59:4216–4218
Weinberg RA (1991) Tumor suppressor genes. Science 254:1138–1146
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
� 2003 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
de Koning, J.P., Mao, JH., Balmain, A. (2003). Novel Approaches to Identify Low-Penetrance Cancer Susceptibility Genes Using Mouse Models. In: Senn, HJ., Morant, R. (eds) Tumor Prevention and Genetics. Recent Results in Cancer Research, vol 163. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55647-0_3
Download citation
DOI: https://doi.org/10.1007/978-3-642-55647-0_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62892-4
Online ISBN: 978-3-642-55647-0
eBook Packages: Springer Book Archive