title: Molecular epidemiology of cancer in immune deficiency.
abstract: Molecular epidemiology may help fill the gap between epidemiological and biological models for cancerogenesis, allowing useful comparisons between series of cases carrying different biological characteristics. The defective regulation of immune responses is probably the common basis of cancer origin in genetically determined immune deficiency (GDID). Lymphomas are the most common neoplasms, showing an extremely high incidence in early age, frequent unusual location (extra-nodal) and histology, and rapid progression and spread with little response to therapy. A high incidence of lymphoma is also found in acquired (AIDS) or iatrogenic (transplant recipients) immune defective patients. The emergence of a malignant clone may be linked to unregulated polyclonal B- or T-cell proliferation and to disturbances in chromosomal rearrangements and in clonal selection, which are unique features of the immune cells regulation. It is useful to compare patterns of malignancies observed in GDIDs and in chromosomal breakage syndromes (CBS). In ataxia-teleangectasia (AT), selective errors at sites of special recombination involved in immune cell rearrangements may account for both immune deficiency and frequent types of malignant transformation. Different cytogenetic alterations and different types of malignancies are more common in Bloom syndrome, and in other GDIDs unrelated to chromosomal fragility, possibly due to different regulatory impairments. Viral infection (EBV, HPV, CMV) is likely to be a factor in any of the above steps. Therefore, individual exposure to viral (or other environmental) agents may be related to frequent location (skin, ano-genital areas, digestive tracts) of nonlymphatic cancers both in some GDIDs and in acquired or iatrogenic immune deficiencies. Cells that are homozygous for GDID are not malignant themselves, but are more likely to undergo new mutations to malignancy, due both to disregulation of the immune system and to environmental agents.
authors.affiliation: Section of Epidemiological Genetics, Istituto Nazionale per la Ricerca sul Cancro, IST Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Strigini
authors.forename: S
authors.initials: S
authors.lastname: Carobbi
authors.forename: R
authors.initials: R
authors.lastname: Sansone
authors.forename: C
authors.initials: C
authors.lastname: Lombardo
authors.forename: L
authors.initials: L
authors.lastname: Santi
mesh_terms: D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000235:genetics / Q000276:immunology; D015994:Incidence; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology