Multiple primary cancer, including transitional cell carcinoma of the upper uroepithelial tract in a multigeneration HNPCC family: molecular genetic, diagnostic, and management implications

Am J Gastroenterol. 2003 Mar;98(3):664-70. doi: 10.1111/j.1572-0241.2003.07329.x.


Objective: We report a multigeneration family where colorectal cancer and cancer of multiple diverse anatomic sites, inclusive of transitional cell carcinoma of the upper uroepithelial tract, were manifested in several relatives.

Methods: A specific pattern of cancer of the colorectum, endometrium, ovary, small bowel, and transitional cell carcinoma, with a vertical distribution of this cancer phenotype through multiple generations, was consonant with a diagnosis of hereditary nonpolyposis colorectal cancer.

Results: Germline mutation testing identified the MSH2 mutation, which segregated with the cancer phenotype. This family study clearly demonstrates the value of genetic testing in the management and treatment decision process.

Conclusions: We document, perhaps for the first time, how molecular genetic testing in hereditary nonpolyposis colorectal cancer can aid in the identification of a potential renal transplant donor for a relative with the MSH2 mutation who is experiencing renal insufficiency secondary to transitional cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Transitional Cell* / diagnosis
  • Carcinoma, Transitional Cell* / genetics
  • Carcinoma, Transitional Cell* / therapy
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA-Binding Proteins*
  • Female
  • Genetic Counseling
  • Genotype
  • Germ-Line Mutation*
  • Humans
  • Kidney Neoplasms* / diagnosis
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / therapy
  • Kidney Transplantation*
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • MutS Homolog 2 Protein
  • Neoplasms, Multiple Primary* / diagnosis
  • Neoplasms, Multiple Primary* / genetics
  • Neoplasms, Multiple Primary* / therapy
  • Pedigree
  • Phenotype
  • Proto-Oncogene Proteins / genetics*


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutS Homolog 2 Protein