c l i n i c a l f o l i o s : d i s c u s s i o n

Hereditary Non-Polyposis Colon Cancer (Lynch Syndrome)



Related narratives:
Hereditary Non-Polyposis Colon Cancer (Lynch Syndrome), Lynch Syndrome II

The etiology of colorectal cancer is heterogeneous, with both environmental and hereditary factors playing roles to varying degrees. About 20% of colorectal cancers have evidence of familial component, with the rest arising sporadically. Hereditary non-polyposis colon cancer (HNPCC), also known as Lynch Syndrome, is the most common hereditary form of colorectal cancer.

Epidemiology and Risk Factors

HNPCC represents 4% to 6% of all colon cancers. The definition of HNPCC has recently been standardized by the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer. Families must have at least three relatives with colorectal cancer, one of whom is a first-degree relative of the other two. Colorectal cancer must involve at least two generations, and at least one case must occur before age 50 years. Recently, it has been shown that HNPCC is caused by defective DNA mismatch repair genes, and someone with this mutation has a 70%-80% lifetime risk of developing colon or rectal cancer. The average age of onset is only 44 years, compared with the average age of sporadic cases, which is in the seventh decade.

Screening, Diagnosis and Treatment

The genetic basis for HNPCC is heterogeneous, with the majority linked to chromosomes 2, 3, and 7. Patients with HNPCC do not develop extensive polyposis (i.e., hundreds of polyps), making identification more difficult. Although their lesions are more commonly right-sided, clinically they present identically to patients with sporadic colon carcinomas. These patients develop colon polyps at a rate similar to the normal population; however, once they develop a polyp, there is more rapid progression to cancer because of the presence of mismatch repair gene(s) defects. The precursor lesion appears as a discrete proximal colonic adenoma, which occasionally appears flat rather than polypoid. A high rate of metachronous cancers indicates the need for a subtotal colectomy as initial treatment.

It is only through careful family profiling of three generations of family that suspicion of HNPCC is generated. The HNPCC syndrome has two subsets: Lynch I, which has no history of associated cancers, and Lynch II, which can present along with other malignancies, more commonly of ovarian or uterine origin. With the multiple-site mutations of HNPCC, genetic testing is used less commonly as a screening tool, so aggressive surveillance in potential patients is warranted. Without genetic testing, first-degree relatives of those affected should have a colonoscopy every year or two, starting at age 20. In those whom the germline mutation is identified, screening colonoscopy should be annual, and women who are carriers should be followed for endometrial or ovarian cancer. These patients may also consider prophylactic colectomy and/or hysterectomy and bilateral salpingo-oophorectomy.

Subtotal colectomy with ileorectal anastomosis is recommended when HNPCC is found because of the high rate of metachronous colorectal cancer.


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Lynch HT. (2000). Lynch syndrome: genetics, natural history, genetic counseling, and prevention. J Clin Oncol, 18(21 Suppl): 19S-31S.

This page was last modified on 17-Jan-2001.