| : Cancer, including head and neck cancer, arises by the interplay between genes and environmental exposure. High penetrance phenotypes usually relate to inherited disorders. Most well-known inherited disorder associated with head and neck cancer is Fanconi Anemia (FA). FA is characterized clinically by congenital abnormalities, bone marrow failure and cancer predisposition, in particular squamous cell carcinoma and acute myeloid leukemia. FA patients have a 500-1,000x increased risk for head and neck cancer. We have studied the hypothesis that young sporadic head and neck cancer patients and non-smoking patients have developed HNSCC since they have an inborn error in the FA pathway (a conglomeration of genes (FANC-genes) involved in DNA damage recognition and repair) Thus far, blood and tissue of nine patients have been tested with mitomycin break assay , the standard functional assay that is used to identify a Fanconi Anemia patient. So far no hidden FA patient was identified. In addition we study the process of field cancerization in FA patients using non-invasive genetic cytology. We could show that in 145 FA patients tested 19 (13%) had developed a field of genetically altered cells. This is a highly significant difference compared to the absence of any change in 200 controls aged 58 and older. This research line will be extended to proof the value of noninvasive genetic cytology to predict cancer. Besides these high penetrance inherited syndromes there are also low penetrance genetic factors. The study of young patients, below 40 yrs. of age with sporadic HNSCC might reveal the these genes. The initial step was taken in this direction by starting a genetic analysis of HNSCC of this patient group to see whether the genetic route to cancer was different compared to that of the older population. |
