The Role of Genetic Predisposition and Environmental Factors in the Occurrence of Multiple Different Solid Tumors. The Experience of the University Hospital of Sienna

  • Francesco Cetta
  • Armand Dhamo
  • Annamaria Azzarà
  • Laura Moltoni
Part of the Updates in Surgery book series (UPDATESSURG)


An inherited predisposition and environmental factors are the main determinants of human malignancies. Although uniquely, they represent the two outer boundaries of cancerogenesis, in most cases they act in combination, in particular when multiple tumors concomitantly affect the same individual or the same kindred. Inherited multi-tumoral syndromes are caused by germline mutations of tumor suppressor genes, which can result in either malignant or benign tumors as well as various nontumoral alterations. However, multiple tumors, i.e. solid tumors that are not causally related to each other, are increasingly observed in the same individual in the absence of genetically determined syndromes. This may simply be due to the increased life expectancy and/or to improvements in the early diagnosis and treatment of tumors, and thus an improved long-term survival after removal of the first tumor. However, at least three modern-day conditions may act as independent factors for the increased occurrence of multiple solid tumors in the same individual:
  1. 1.

    Radiotherapy and/or chemotherapy, or a combination of both, are increasingly used at the highest doses. Powerful antimetabolic, antiblastic, antibiotic drugs, together with immunosuppression and immunomodulation facilitate the occurrence of second tumors, sometimes within the first decade after treatment.

  2. 2.

    Environmental pollution or inappropriate waste treatment has increased our exposure to carcinogens and other toxic agents. This has lead to increased frequencies of some cancers, particularly in subjects genetically more sensitive to these agents. Polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines are known carcinogens found in cigarette smoke and in air pollution. Transitional metals (Fe, Cr, Cu, Pb, Cd, V), fibers such as asbestos, pollutants from metropolitan areas, as well as long-term and long-distance side-effects of nuclear accidents (such as Chernobyl or similar nuclear disasters) are certainly responsible for an increased number of tumors, i.e., in addition to those usually occurring in the natural history of each individual.

  3. 3.

    Patients undergoing organ transplantation, such as liver transplantation, in the treatment of malignant disease require immunosuppression. In these patients, in addition to recurrence of the primary tumor, new tumors, related to chronic immunosuppression, may develop.



Papillary Thyroid Carcinoma Germline Mutation Familial Adenomatous Polyposis Adenomatous Polyposis Coli Familial Adenomatous Polypo Patient 
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Copyright information

© Springer-Verlag Italia 2009

Authors and Affiliations

  • Francesco Cetta
    • 1
  • Armand Dhamo
    • 1
  • Annamaria Azzarà
    • 1
  • Laura Moltoni
    • 1
  1. 1.Department of SurgeryUniversity of SiennaSiennaItaly

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