title: An information-theoretic analysis of genetics, gender and age in cancer patients.
abstract: Germline genetics, gender and hormonal-signaling pathways are all well described modifiers of cancer risk and progression. Although an improved understanding of how germline genetic variants interact with other cancer risk factors may allow better prevention and treatment of human cancer, measuring and quantifying these interactions is challenging. In other areas of research, Information Theory has been used to quantitatively describe similar multivariate interactions. We implemented a novel information-theoretic analysis to measure the joint effect of a high frequency germline genetic variant of the p53 tumor suppressor pathway (MDM2 SNP309 T/G) and gender on clinical cancer phenotypes. This analysis quantitatively describes synergistic interactions among gender, the MDM2 SNP309 locus, and the age of onset of tumorigenesis in p53 mutation carriers. These results offer a molecular and genetic basis for the observed sexual dimorphism of cancer risk in p53 mutation carriers and a model is proposed that suggests a novel cancer prevention strategy for p53 mutation carriers.
authors.affiliation: The Institute for Advanced Study, Princeton, New Jersey, United States of America.
authors.forename: Gurinder Singh
authors.initials: GS
authors.lastname: Atwal
authors.forename: Raúl
authors.initials: R
authors.lastname: Rabadán
authors.forename: Guillermina
authors.initials: G
authors.lastname: Lozano
authors.forename: Louise C
authors.initials: LC
authors.lastname: Strong
authors.forename: Mariëlle W G
authors.initials: MW
authors.lastname: Ruijs
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Johanna
authors.initials: J
authors.lastname: Tommiska
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomäki
authors.forename: Gaelle
authors.initials: G
authors.lastname: Bougeard
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Gareth L
authors.initials: GL
authors.lastname: Bond
mesh_terms: D000367:Age Factors; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008490:Medical Informatics; D008962:Models, Theoretical; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D012727:Sex Characteristics; D012737:Sex Factors; D015398:Signal Transduction