1.1. Head and neck cancer predisposition
Cancer, including head and neck cancer, arises by the interplay between genes and environmental exposure. High penetrance phenotypes usually relate to inherited disorders, and also for head and neck cancer these syndromes exist. Fanconi anemia (FA) is an inherited disorder with congenital abnormalities 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 are studying genetic characteristics of FA patient head and neck tumors and found a relatively low prevalence of human papillomavirus induced tumors (below 10%) as compared to literature data. Besides these high penetrance inherited syndromes there also low penetrance genetic factors. Patients with sporadic head and neck cancers show a susceptibility phenotype to bleomycin induced double stranded DNA breaks as compared to the normal population. We focus on this phenotype that is caused for 75% by inheritable factors.
- Key papers:
Cloos, J., Nieuwenhuis, E. J. C., Boomsma, D. I., Kuik, D. J., Van Der Sterre, M. L. T., Arwert, F., Snow, G. B., and Braakhuis, B. J. M. Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes. J. Natl. Cancer Inst., 91: 1125-1130, 1999.
- Adema, A. D., Cloos, J., Verheijen, R. H., Braakhuis, B. J., and Bryant, P. E. Comparison of bleomycin and radiation in the G2 assay of chromatid breaks. Int. J. Radiat. Biol., 79: 655-661, 2003.
- van Zeeburg, H. J., Snijders, P. J., Pals, G., Hermsen, M. A., Rooimans, M. A., Bagby, G., Soulier, J., Gluckman, E., Wennerberg, J., Leemans, C. R., Joenje, H., and Brakenhoff, R. H. Generation and molecular characterization of head and neck squamous cell lines of fanconi anemia patients. Cancer Res, 65: 1271-1276, 2005.
- Cloos, J., de Boer, W. P., Snel, M. H., van den Ijssel, P., Ylstra, B., Leemans, C. R., Brakenhoff, R. H., and Braakhuis, B. J. Microarray analysis of bleomycin-exposed lymphoblastoid cells for identifying cancer susceptibility genes. Mol Cancer Res, 4: 71-7, 2006.
- Dirksen, E. H., Cloos, J., Braakhuis, B. J., Brakenhoff, R. H., Heck, A. J., and Slijper, M. Human lymphoblastoid proteome analysis reveals a role for the inhibitor of acetyltransferases complex in DNA double-strand break response. Cancer Res, 66: 1473-80, 2006.
- van Zeeburg, H.J.T., Snijders, P.J.F., Wu, Th., Gluckman, E., Soulier, J., Surralles, J., Castella, M., van der Wal, J.E., Wennerberg, J., Califano, J., Velleuer, E., Dietrich R., Ebell W., Bloemena E., Joenje, H., Leemans, C.R., Brakenhoff, R.H. Clinical and Molecular Characteristics of Squamous Cell Carcinomas From Fanconi Anemia Patients. J.Natl. Cancer Inst. 100:1649-1653, 2008.