In Lynch syndrome, colon cancer typically occurs in the mid-40s, with few polyps, and a predominance of right-sided colon cancer. Colonoscopy (vs. sigmoidoscopy) is the appropriate screening tool. The distinguishing features of Lynch syndrome are early onset cancers as well as multiple primary tumors in affected individuals. This syndrome is most often caused by an abnormality in one of several mismatch DNA repair pathway genes (most often MLH1 or MSH2; occasionally MSH6, or more rarely, PMS2).

The risk for colon cancer in Lynch syndrome is about 80%. Women who have a mutation in one of the syndrome’s associated genes also have about a 35%-40% risk of endometrial cancer and up to a 10% risk of ovarian cancer. Persons with this syndrome also have a very high risk (>50%) for additional primary colorectal cancers and a small risk for upper GI cancers, transitional cell carcinomas of the renal pelvis, and cancers of the pancreato-biliary tract. The strictest diagnosis of Lynch syndrome is based on the “Amsterdam 3-2-1” criteria of having three affected family members with colon cancer, at least two generations affected, one case diagnosed before age 50, and one affected being a first-degree relative of the other two. Each child or sibling of a person with a mutation in one of the Lynch syndrome genes has a 50% (1:2) chance of inheriting the mutation.

Figure 27-1 depicts the family history in the form of a pedigree. Jane and her husband have a 16-year-old daughter, Kim, and two sons, John, age 23 and Steven, age 20. Jane has a 43-year-old sister, Anne, who does not have children. Jane and Anne’s only brother, Tom, died of colon cancer nearly six years ago, shortly after being diagnosed with the disease at age 45. Tom has a 31-year-old son, Scott, who does not have children. Jane’s 77-year old mother was treated for colon cancer in her cecum at age 65. The mother also had a hysterectomy and removal of both ovaries at age 50 for uterine fibroids, as did Jane’s only maternal female cousin, Linda, at age 45. Linda does not have children, neither does her 44-year-old brother, but their 49-year-old brother has two daughters, ages 18 and 20. Linda’s mother, age 75, had uterine cancer at age 49. Jane’s other maternal aunt died at age 29 in an automobile accident. The only maternal uncle, age 74, has not had cancer. The maternal grandmother had stomach cancer at age 55 and died of disease at age 56. She had one sibling, a brother who died at age 78 of heart disease. The maternal grandfather died at age 28 of leukemia. Jane had no further knowledge of his side of the family. There are no cancers in the paternal lineage other than a lung cancer at age 85 in the paternal grandfather.

At each counseling session the family was offered the support of the cancer center’s social worker and psychologist. Jane presented to clinic with her husband, expressing that her major motivation for the genetic consultation was to learn about her daughter’s risk for colon cancer. Jane states that she is not concerned about her sons having colon cancer, because they resemble her husband’s side of the family physically and in their personalities, in contrast to her daughter who is the “spitting image
of me.” Jane also believes that her cousin Linda is not at risk for colon cancer since Linda’s mother, Jane’s maternal aunt, has not had the disease.

Jane and her husband received extensive counseling from the GCRA multidisciplinary team regarding Lynch syndrome and its implications for Jane’s health care as well as for their children and other relatives. The couple decided that trying to identify the cause of the colon cancers was something they wanted to pursue. After discussing this with their family, they returned to the clinic anxious to proceed with genetic testing.