title: No paradox, no progress: inverse cancer comorbidity in people with other complex diseases.
abstract: In the past 5 years, several leading groups have attempted to explain why individuals with Down's syndrome have a reduced risk of many solid tumours and an increased risk of leukaemia and testicular cancer. Niels Bohr, the Danish physicist, noted that a paradox could initiate progress. We think that the paradox of a medical disorder protecting against cancer could be formalised in a new model of inverse cancer morbidity in people with other serious diseases. In this Personal View, we review evidence from epidemiological and clinical studies that supports a consistently lower than expected occurrence of cancer in patients with Down's syndrome, Parkinson's disease, schizophrenia, diabetes, Alzheimer's disease, multiple sclerosis, and anorexia nervosa. Intriguingly, most comorbidities are neuropsychiatric or CNS disorders. We provide a brief overview of evidence indicating genetic and molecular connections between cancer and these complex diseases. Inverse comorbidity could be a valuable model to investigate common or related pathways or processes and test new therapies, but, most importantly, to understand why certain people are protected from the malignancy.
authors.affiliation: Department of Medicine, University of Valencia, Centro de Investigación Biomédica en Red en el area de Salud Mental (CIBERSAM), Valencia, Spain. rafael.tabares@uv.es
authors.forename: Rafael
authors.initials: R
authors.lastname: Tabarés-Seisdedos
authors.forename: Nancy
authors.initials: N
authors.lastname: Dumont
authors.forename: Anaïs
authors.initials: A
authors.lastname: Baudot
authors.forename: Jose M
authors.initials: JM
authors.lastname: Valderas
authors.forename: Joan
authors.initials: J
authors.lastname: Climent
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez-Beneyto
authors.forename: Salvador
authors.initials: S
authors.lastname: Martínez
authors.forename: John L
authors.initials: JL
authors.lastname: Rubenstein
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D000856:Anorexia Nervosa / Q000235:genetics; D002898:Chromosomes, Human, Pair 8; D015897:Comorbidity; D004314:Down Syndrome / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000517:prevention & control*; D020890:Neuregulin-1 / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1