1-5% of all patients presenting with
colorectal cancer, have an underlying
genetic predisposition with an autosomal dominant of pattern of inheritance. Recently the underlying molecular genetic pathway of this syndrome known as HNPCC (
hereditary nonpolyposis colorectal cancer) has been characterized: the predisposition is due to a pathogenic mutation in one of the DNA mismatch-repair genes.
Colorectal cancers are the leading characterisitic of the syndrom and are frequently encountered at a young age of onset. However,
endometrial cancer,
stomach cancer, small bowel
cancer, urinary tract cancer and
skin cancer among others are also inherent to the syndrome. Based on the identification of the underlying molecular genetic pathway, predictive testing has become an option. Once the family-specific underlying pathogenic mutation in one of the DNA mismatch-repair genes has been identified in a proband, at-risk family members may be offered
DNA testing with an unequivocal answer to if or if not they have inherited the increased
cancer susceptibility. Multiple facets of family
DNA testing require a multidisciplinary approach integrating clinicians, geneticists, psychologists, molecular biologist and pathologists. Mutations are identified in a rate of 50-60% of families complying with the Amsterdam criteria for HNPCC. The incidence of recta
cancer in HNPCC has as yet not clearly been defined, due to a lack of unequivocal data. In a retrospective analysis (submitted)
rectal cancers were encountered in 30% of the HNPCC patients. Half of the patients affected developed metachronous
colon cancers. It is essential to address the issue of prophylactic surgery in HNPCC patients presenting with
colorectal cancer: Prospective data is required in order to decide which of the options is more beneficial for the HNPCC patient presenting with his first colorectal primary: subtotal
colectomy and ileorectal anastomosis versus
restorative proctocolectomy. It is evident that apart from the more clinical data quality of life data must be evaluated in this study.