Fitzgibbons R J, Lynch H T, Stanislav G V, Watson P A, Lanspa S J, Marcus J N, Smyrk T, Kriegler M D, Lynch J F
Ann Surg. 1987 Sep;206(3):289-95. doi: 10.1097/00000658-198709000-00007.
Primary genetic factors are etiologic in at least 5-10% of patients with colon cancer. The polyposis syndromes (FPC) are easily identified examples because of the spectacular number of polyps. The hereditary nonpolyposis syndromes (HNPCC), although five times more common than FPC, are usually not recognized because they do not have such a distinctive clinical, premonitory genetic marker. Colorectal cancer expression was surveyed in 10 extended, thoroughly documented HNPCC kindreds. One hundred sixteen patients were found to have 183 colorectal cancers. Despite the striking family history, less than 5% were correctly treated by subtotal colectomy. This provided a unique opportunity to study the natural history. Five findings differed significantly (p less than 0.05) from patients with sporadic colon cancer: (1) mean age of initial colon cancer diagnosed was 45.6 years; (2) 69.1% of first colon cancers were located proximal to the splenic flexure of the colon; (3) 18.1% had synchronous colon cancer; (4) 24.2% had metachronous colon cancer develop with life table analysis showing the risk for a metachronous lesion at 10 years to be 40%; and (5) only 23.3% of cancers were located in the sigmoid colon or rectum. Based on this data, it is recommended that the family history of all patients with a newly diagnosed colon cancer be evaluated for evidence of this syndrome. If an autosomal dominant inheritance pattern emerges, an in-depth genetic investigation is indicated. When HNPCC is confirmed, the following recommendations apply: a subtotal abdominal colectomy is indicated at the time of the initial colon cancer because of the risk of synchronous and metachronous lesions. The rectum should be spared in favor of careful lifetime surveillance because of the proclivity for proximal colon cancer involvement. As yet unaffected members of a newly diagnosed HNPCC kindred who are in the "direct genetic line" should be cautioned that they are at 50% risk and must begin an intensive surveillance program beginning in the third decade with careful attention to the right colon. Patients from newly diagnosed HNPCC families who have had a previous conventional colectomy for colon cancer should, at the very least, enter an intensive surveillance program; a prophylactic completion subtotal colectomy should be considered for patients who are less than totally compliant.
原发性遗传因素在至少5%-10%的结肠癌患者中是病因性的。息肉病综合征（FPC）是容易识别的例子，因为息肉数量惊人。遗传性非息肉病综合征（HNPCC）虽然比FPC常见五倍，但通常未被识别，因为它们没有如此独特的临床、先兆性遗传标记。对10个经过充分记录的HNPCC大家族进行了结直肠癌表达情况的调查。发现116名患者患有183例结直肠癌。尽管有明显的家族病史，但不到5%的患者通过结肠次全切除术得到了正确治疗。这提供了一个研究自然病史的独特机会。与散发性结肠癌患者相比，有五项发现有显著差异（p<0.05）：（1）首次诊断出结肠癌的平均年龄为45.6岁；（2）69.1%的首例结肠癌位于结肠脾曲近端；（3）18.1%有同时性结肠癌；（4）24.2%有异时性结肠癌发生，生命表分析显示10年时异时性病变的风险为40%；（5）只有23.3%的癌症位于乙状结肠或直肠。基于这些数据，建议对所有新诊断为结肠癌的患者的家族病史进行评估，以寻找该综合征的证据。如果出现常染色体显性遗传模式，则需进行深入的基因调查。当HNPCC得到证实时，适用以下建议：由于存在同时性和异时性病变的风险，在首次诊断出结肠癌时应进行腹部结肠次全切除术。应保留直肠，以便进行仔细的终身监测，因为近端结肠癌受累的倾向较大。新诊断的HNPCC大家族中尚未受影响的处于“直系基因系”的成员应被告知，他们有50%的风险，必须从三十岁开始启动强化监测计划，并密切关注右半结肠。新诊断的HNPCC家族中曾因结肠癌接受过传统结肠切除术的患者，至少应进入强化监测计划；对于不完全依从的患者，应考虑进行预防性结肠次全切除术。
