%0 Journal Article
%T Hereditary and environmental epidemiology of sarcomas
%A David M Thomas
%A Sharon A Savage
%A Gareth L Bond
%J Clinical Sarcoma Research
%D 2012
%I BioMed Central
%R 10.1186/2045-3329-2-13
%X Readers of this series will be struck by the degree to which familial sarcoma syndromes have broadly contributed to understanding of cancer biology, including the fundamentals of cell cycle regulation and maintenance of the genome integrity. For example, sarcomas comprise the single most common cancer type seen in families with Li-Fraumeni syndrome, which is most commonly caused by germline mutations in TP53. The study of TP53 biology in sarcomas has contributed to our knowledge of this crucial tumour suppressor that is the most somatically mutated gene in human cancers. The story of p53 demonstrates the contribution of mouse models of human disease (see papers by Ng et al. [2]; and Post [3]). Individuals with retinoblastoma, an inherited cancer syndrome, have a 500-fold increased incidence of bone sarcomas, predominately osteosarcoma (reviewed here by Kleinerman et al. [4]). Long before the gene responsible for this syndrome (RB1) was identified, epidemiologic studies of affected families led to the ¡®two-hit¡¯ hypothesis of tumor suppressor genes [5]. Other important examples of the hereditary sarcomas described in this series include gastrointestinal stromal tumors [6] and malignant peripheral nerve sheath tumors [7].Despite (or perhaps because of) being rare, sarcomas have acted as sentinel events that are epidemiologically noteworthy. While it is sometimes difficult to distinguish sporadic from hereditary breast cancer, a sarcoma occurring twice within the one family is epidemiologically striking. Another feature of sarcomas is the relatively young age of onset. Cancer is generally a disease of ageing: the average age of cancer diagnosis in Western countries is in the late 60s. By contrast, sarcomas affect younger populations, while some sarcomas (primarily rhabdomyosarcoma, osteosarcoma, and Ewing sarcoma) are essentially diseases of childhood and adolescence. Epidemiologically, early onset cancer usually suggests predisposing factors are at play, whether enviro
%U http://www.clinicalsarcomaresearch.com/content/2/1/13