emedicine: Hereditary Colorectal Cancer (Lynch Syndrome)

Hereditary Colorectal Cancer

"Mortality/Morbidity

Although not everyone who inherits the gene for hereditary nonpolyposis colorectal cancer (HNPCC) develops colorectal cancer, individuals with Lynch syndrome have a 70-80% lifetime risk of developing colon cancer. Of these cancers, two thirds occur in the proximal colon (proximal to the splenic flexure). In approximately 45% of affected individuals, multiple synchronous and metachronous colorectal may occur within 10 years of resection.
Other cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC) (Lynch Syndrome) include the following:

• Endometrial cancer: The lifetime risk is 30-40% by age 70 years. The average age at diagnosis is 46 years. Half of patients with both colon and endometrial cancer present with endometrial cancer first.
• Ovarian cancer: The lifetime risk is 9-12% by age 70 years. The average age at diagnosis is 42.5 years. Approximately 30% of these tumors present before age 40 years.
• Gastric cancer: The lifetime risk is around 13% (higher in Asians). The mean age at diagnosis of gastric cancer is 56 years; intestinal-type adenocarcinoma is the most commonly reported pathology, especially in Asian countries such as Japan, Korea, and China.
• Transitional cell carcinoma: The lifetime risk is 4-10%. This principally affects the upper urinary tract (ureters and renal pelvis).
• Adenocarcinoma of the small bowel cancers: The lifetime risk is 1-3%. These occur most commonly in the duodenum and jejunum.
• Glioblastoma: The lifetime risk is 1-4%. Also known as Turcot syndrome, this is a variant of hereditary nonpolyposis colorectal cancer (HNPCC) (see below).
• Malignancies of the larynx, breast, prostate, liver, biliary tree, pancreas, and the hematopoietic system are more common in patients with hereditary nonpolyposis colorectal cancer (HNPCC).

Table 2. Incidence of different types of cancers between individuals with Lynch syndrome and those in the general population. (Open Table in a new window)

Type of Cancer	General Population Risk (by age 70 y)	Lynch Syndrome Risk (by age 70 y)
Endometrial	1.5%	30-40%
Ovarian	1%	9-12%
Upper Urinary Tract	Less than 1%	4-10%
Stomach	Less than 1%	13% (higher in Asians)
Small Bowel	Less than 1%	1-3%
Brain	Less than 1%	1-4%
Biliary Tract	Less than 1%	1-5%	......cont'd