Trial Information

Hereditary Nonpolyposis Colorectal Cancer in Taiwan－Related Genetic Study and Clinical Applications

HNPCC is an autosomal dominant disease that is clinically characterized by the development
of colorectal cancer (CRC) at an early age (mean age 44 years old). Four genes have been
known to be related to this hereditary disease. It shows an excess of synchronous and
metachronous tumors as well as a preponderance of right-sided tumors (70%). Another feature
has been seen among the families of the HNPCC patients is the occurrence of adenocarcinomas
at other sites (particularly at the endometrial, ovary, stomach, pancreas, ureter, renal
pelvis, and skin). Difficulties arise in distinguishing environmental factors and genetic
predisposition for familial clustering of CRC. The discovery of HNPCC germline mutations has
been momentous in that it enables a clear distinction between carriers and noncarriers for
those who were previously assigned a 50% risk of germline mutation. The informed consent
provided by patients is important for the process of familial study and the search for
germline mutations, these will further provide information for education and counseling.
HNPCC has been reported to be responsible for about 1% to 13% of all CRC. The frequency of
HNPCC varies by geographical areas. The true incidence of HNPCC in Taiwan area is unclear.
From year 1995 to 2000, 50 out of 4500(1.1%) patients were HNPCC according to the Amsterdam
I criteria. MMR gene databases are crucial to understand the relationship between genotype
and phenotype. Kindred sharing the same mutations but living in different places will
provide the information to assess the contribution of environmental factors to colorectal
carcinogenesis. The related clinical and basic researches are thus important for
understanding the mutation spectrum of MMR genes, interaction between oncogenes, tumor
suppressor genes, and roles of genetic polymorphisms in modifying MMR genes in Taiwan.