A polygenic model of inherited predisposition to cancer

Tommaso A. Dragani, Federico Canzian, Marco A. Pierotti

Research output: Contribution to journalArticlepeer-review


Polygenic inheritance of predisposition to cancer is demonstrated in experimental animals for different tumor types. Genetic susceptibility to hepatocarcinogenesis, lung tumorigenesis, skin and intestine carcinogenesis, and plasmacytomagenesis is determined by inheritance of multiple cancer predisposition and resistance alleles, whose chromosomal locations have been found by genetic linkage analysis. In some of these experimental models, genetic heterogeneity has also been reported. In humans, increased risk of lung cancer associated with multiple genes coding for drug metabolizing enzymes, increased risk of cancer in relatives of cancer patients, and genetic heterogeneity are compatible with polygenic inheritance of cancer predisposition. Polygenic inheritance based on the combination of multiple alleles that give predisposition and resistance to cancer would predict a very high risk of cancer in carrier individuals and a marginal increase in the relative risk of cancer in the progeny of the cancer patients. Therefore, predisposition to cancer may be genetically determined even in the absence of familial clustering of cases.

Original languageEnglish
Pages (from-to)865-870
Number of pages6
JournalFASEB Journal
Issue number8
Publication statusPublished - Jun 1996


  • animal disease susceptibility/linkage
  • disease models
  • genetics/mice
  • inbred strains/models

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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