Hereditary nonpolyposis colorectal cancer with gynecologic malignancies: Report of two families in Taiwan

Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome, is characterized by germline and somatic mutations of DNA mismatch repair genes with dominant inheritance of site-specific colorectal cancer or colorectal cancer plus cancers of extracolonic sites. We describe two Taiwanese HNPCC families with members who had predominantly gynecologic malignancies. In one family, the 53-year-old proband was found to have five synchronous and metachronous tumors of the genitourinary system, which included endometrial adenocarcinoma, cervical squamous cell carcinoma, ureteral and bladder transitional cell carcinoma, and ovarian teratoma. Fourteen of her first- and second-degree relatives were victims of genitourinary and gastrointestinal malignancies. The other family was characterized by four sisters who developed endometrial adenocarcinomas at young ages (36-42 yr). Their father died of both stomach cancer and colon cancer at age 47. The diagnosis of HNPCC was confirmed in this family by genetic analysis. A heterozygous germline mutation (G5 to G6 frame-shift at 183-187) of the hMSH2 (human MutS homolog 2) gene was identified in white blood cells of all the affected family members. The frequent presentation of genitourinary cancers in HNPCC highlights the importance of family-history taking in patients with gynecologic cancers and a genetic diagnosis of HNPCC.