遗传性非息肉病性大肠癌家系研究

目的;分析遗传性非息肉病性大肠癌家系肿瘤的基因表达及特点,诊治经验。方法：分析24个遗传性非息肉病性大肠癌家系的诊断,治疗和随访结果。记录恶性肿瘤部位,确诊年龄,同时性和（或）异时性癌,肿瘤的病理学资料,应用聚合酶链反应和单链构像多态性方法检查家族成员hMLH1和hMSH2各外显子,对可疑突变片段测序。结果：24个家系中共有患者75例,共诊断各种恶性肿瘤125个,主要有大肠癌,胃癌,子宫内膜癌等,本组诊断大肠癌患者64例（异时性多原发大肠癌16例）,24％的大肠癌患者首次手术10年内再发异时性大肠癌,发现2个家系携带hMSH2基因,1个家系携带hMLH1基因种系突变,均产生截短蛋白,3个家族中已发现12例突变基因携带者,结论：本病主要特点是恶性肿瘤早发,多发;结肠直肠癌,尤其是右侧结肠癌为主,多原发癌,尤其是多原发性大肠癌多见,家族发病年龄逐代提前,常规肠段切除手术可能不适于此类大肠癌的治疗。已发现2个家系有hMSH2基因,1个家系有hMLH1基因突变。

Genealogical research of hereditary nonpolyposis colorectal cancer

Objectives To analyse the diagnosis and treatment of 24 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds and report mismatch repair gene mutations. Methods The diagnosis, treatment and follow up of 24 HNPCC kindreds were reviewed retrospectively, cancer incidence and spectrum were recorded. Clinical characteristics and treatment were analyzed. Peripherial blood and genomic DNA were extracted from family members who had provided informed consent. PCR and SSCP were used to screen coding regions of the hMLH1 and hMSH2 genes. Variant bands were sequenced by 377 DNA sequencer after purification. Results One hundred and 25 malignant neoplasms were diagnosed in 75 patients (multiple cancers in 24) with an average age of 51 years in 24 pedigrees. The onset of the disease occurred earlier than expected with the passing of each generation within large kindreds. The neoplasm mainly included colonic cancer (63 patients), rectal cancer(21), stomach cancer(13),endometric cancer(7), and esophageal cancers(6). 84% patients received radical operations. Of 64 patients with colorectal cancer 16 had metachronous colorectal cancer. 24% colorectal patients developed metachronous cancer within 10 years after initial operation and neceived re operation. In 3 detected families with germline hMSH2 and hMLH1 mutations resulting in truncated protein, 12 carriers were found. Conclusions The main characteristics of hereditary nonpolyposis colorectal cancer include early onset and frequence of cancer; predominance of colorectal cancer, especially right sided colonic cancer; frequency of multiple primary cancer, especially colorectal cancer; and age anticipation in large HNPCC pedigrees. Segmental resection of colorectal cancer is not suitable for colorectal cancer patient in HNPCC kindred. Intensive follow up is important for all patients and possible gene carriers.