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

The purpose of this study is to establish the HNPCC related information in Taiwan, and to characterize relevant susceptibility genes related to colorectal cancer to provide better disease control for the high-risk people. To accomplish this objective, we will collect detailed information of the HNPCC patients and their families from the collaborative hospitals and relate the information to the risk of CRC in order to provide sound disease control system in Taiwan.

Study Overview

• Status: Unknown
• Conditions: Hereditary Nonpolyposis Colorectal Cancer

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1014

Contacts and Locations

Study Locations

• Taiwan
  • Miaoli County, Taiwan, 350
    • Division of Biostatistics and Bioinformatics, National Health Research Institites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The HNPCC patients and their families from the collaborative hospitals and relate the information to the risk of CRC in order to provide sound disease control system in Taiwan

Description

Inclusion Criteria:

• Select all affected individuals. If the affected is unavailable, select the spouse and adult children (20+) of these unavailable affected individuals.

• Select unaffected individuals in the following priority order:

  1. study both parents of the affected individuals;
  2. if parents are not available, study up to two siblings of each missing parent (if both parents are deceased, study four siblings - two from each parent);
  3. study up to five unaffected siblings (age 20 or older) of the affected individual; if more than five siblings are available for study, select the siblings from oldest to youngest;
  4. study up to three children (age 20 or older) of the affected individual; again, select the three oldest children if more than three are available;
  5. if the two affected individuals in the multiplex family are not siblings, (first cousins, for example, then study common grandparents - if common grandparents are not available, study siblings of these grandparents) when children of the affected individual's are studied, the child's unaffected parent will also be selected for study.

Exclusion Criteria:

• N/A

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: Chang Gung Memorial Hospital
• Investigators: Study Director: Chao Hsiung, PhD., Division of Biostatistics and Bioinformatics, National Health Research Institites; Study Director: Rei-Ping Tang, PhD., Colorectal Section, Chang Gung Memorial Hospital; Study Director: Ling-Ling Hsieh, PhD., Department of Public Health, Chang Gung University

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: December 5, 2005
• First Submitted That Met QC Criteria: December 5, 2005
• First Posted (Estimate): December 6, 2005

Study Record Updates

• Last Update Posted (Estimate): April 7, 2016
• Last Update Submitted That Met QC Criteria: April 5, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis
• Other Study ID Numbers: EC9012005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No