MDACC Study Summary DM94-060

Study Summary
No. DM94-060:.......Bladder; Colorectum; Endometrium; Kidney; Skin; Syndrome; Uterus......Patrick Lynch......Gastroenterology/Hepatology and Nutrition

Study Summary Title



Study Summary Number:	DM94-060

Study Title:	The Molecular Predisposition to Hereditary Nonpolyposis Colon Cancer

Physician

New Patient Referral



Name:	Patrick Lynch	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Gastroenterology/Hepatology and Nutrition	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-5073 Contact us about clinical trials

General Information



Disease Group:	Bladder Colorectum Endometrium Kidney Skin Syndrome Uterus	Supported By:	National Cancer Institute

Phase of Study:	N/A	Return Visit:	Not applicable

Treatment Agents:	None	Home Care:	Not applicable

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	Not applicable


Description/ Intervention:	Unavailable

Study Objectives / Outcomes

1. In existing HNPCC families, to perform molecular genetic testing for mismatch repair gene mutations in patients diagnosed with colorectal (CRC) and/or extra colonic cancers that are known to be part of the HNPCC syndrome, utilizing germ line tissues (DNA extracted from leukocyte or solid tissue).
2. To identify, through a consecutive series of CRC and/or other HNPCC –related cancer patients, the frequency of mismatch repair gene mutations in subjects with no immediate family history of HNPCC-related cancers, those with modest familial aggregations of HNPCC- related cancers, and those whose family history is compatible with HNPCC.
3. To assist in the development of quality assurance profiles of molecular testing by comparing mutation analyses performed at the UTMDACC molecular laboratory (Marsha Frazier, Ph.D.), and other CLIA certified laboratories including City of Hope and Myriad Genetics.
4. To evaluate the sensitivity and specificity of various combinations of family history and age at onset for predicting HNPCC carrier status.
5. To determine if genetic polymorphisms in other genes, in combination with diet and lifestyle, influence age associated risk for HNPCC.
6. To validate the microsatellite mutant frequencies quantified by Small-Pool PCR, developed by Mary Coolbaugh-Murphy, Ph.D., Research Fellow, Epidemiology and Michael J. Siciliano, Ph.D., Professor of Molecular Genetics, UTMDACC, by conducting HPRT mutation frequency analysis on 15 paired sets of peripheral blood lymphocyte clones.
7. To examine germline de novo mutation rates amongst carriers of pathogenic mismatch repair mutations.
8. To test for association of de novo mutational events with anticipation in HNPCC offspring.
9. To examine germline de novo mutation rates amongst HNPCC family members not carrying the mutation.
10. To recruit 18 non-HNPCC quartet families (i.e. parents and two offspring not carrying a mismatch repair gene mutation) to examine germline de novo mutation rates amongst non-HNPCC quartets and to examine differences in mutational load between offspring of HNPCC parents and non-HNPCC offspring.

Study Status Information



Study Activation / Registration Date:	09/13/1994

IRB Review and Approval Date:	12/10/2007

Study Type:	Laboratory

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) All patients with a new referral for a diagnosis of colorectal cancer (adenocarcinoma) and/or HNPCC-related cancers at the UTMDACC will be considered potentially eligible for this study regardless of prior treatment.

2) Families maintained at the UTMDACC Hereditary Colon Cancer Registry that have a known germline mutation in a mismatch repair gene or contain two or more first degree relatives diagnosed with CRC and/or any HNPCC-related cancers, one of whom must be less than or equal to 50 years at diagnosis.

3) First-degree and more distant relatives of individuals diagnosed with CRC and/or any HNPCC-related cancers from either of the groups in 1 and 2 (above).

4) Any patient diagnosed with CRC and/or any HNPCC-related cancers less than or equal to 45 years of age.

5) Greater than or equal to age 18 at time of study.

6) Able to provide informed consent to participate in this study indicating that they are aware of the investigational nature, in keeping with the policies of this hospital.

7) Non-HNPCC quartets, defined as parents and two offspring who do not carry a mismatch repair gene mutation. These non-HNPCC quartets should have no personal history of cancer, nor cancer in any first degree relatives of the quartet members, nor history of trinucleotide repeat syndromes. Non-HNPCC parents in a quartet should be less than 34 years old at the time the offspring were born.

Exclusion Criteria:

1) Diagnosis of current major psychiatric disorder, per DSM-III-R (or DSM IV).

2) Age less than 18 years at time of enrollment.

Links

Registration Number: NCT01447199
Study Information on Clinical Trials Registry (clinicaltrials.gov)