J Formos Med Assoc 2001 • Vol 100 • No 4 269 Hereditary Nonpolyposis Colorectal Cancer with Gynecologic Malignancies (J Formos Med Assoc 2001;100:269–73) Key words: hereditary nonpolyposis colorectal cancer DNA mismatch repair gene gynecologic malignancy Taiwan Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, 1 Department of Biology and Anatomy, National Defense Medical Center, Taipei, and 2 Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington DC, USA. Received: 20 March 2000. Revised: 23 May 2000. Accepted: 11 July 2000. Reprint requests and correspondence to: Dr. Tang-Yuan Chu, Department of Obstetrics and Gynecology, Tri-Service General Hospital, 325, Section 2, Chengong Road, Nei-Hu, Taipei, Taiwan. HEREDITARY NONPOLYPOSIS COLORECTAL CANCER WITH GYNECOLOGIC MALIGNANCIES: REPORT OF TWO FAMILIES IN TAIWAN Chi-Huang Chen, Rui-Len Huang, 1 Mu-Shien Yu, Lee-Jun C. Wong, 2 Trong-Fei Chao, 1 and Tang-Yuan Chu Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal inherited cancer syndrome [1] characterized by germline and somatic mutations of DNA mismatch repair genes (eg, hMSH2, the human MutS homolog 2 gene, hMLH1 and others) [2–4] and subsequent accumulation of DNA replication errors (usually indicated by microsatellite instability) and evolution of cancer clones [5, 6]. Cancers inherited in HNPCC are usually early onset, multifocal, familial clustered and, in the case of colorectal carcinoma, proximal predominant. HNPCC is also characterized by clustering of cancers at extracolonic sites, such as the Abstract: 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 genitouri- nary 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. endometrium, ovary, and urinary system [1, 7]. We de- scribe two HNPCC families in which gynecologic malig- nancies were the predominant presentations. The proband of one family had primary cancers of the endometrium, ureter, and cervix, and teratoma of the ovary. Her family history revealed typical HNPCC with cancers of the colon, endometrium, bladder, kidney, ureter, and pancreas affecting 14 family members of two successive generations. The father of the other family had died from cancer of the colon and stomach, and four of his daughters had developed adenocarcinoma of the endometrium at early ages (mean, 40 yr). CASE REPORTS