Hereditary cancers

About 10% of several adult cancers, including breast, ovarian or colon cancer, is due to hereditary causes. Mutations in both BRCA1 and BRCA2 are characterized by predisposition to breast cancer and ovarian cancers, as well as other cancers. Specifically, women with a germline BRCA mutation have about an 87% lifetime risk of breast cancer, and a 10-60% lifetime risk of ovarian cancer. The BRCA genes are inherited in an autosomal dominant fashion. Germline mutations in one of three genes (MLH1, MSH2 and MSH6) cause hereditary non-polyposis colon cancer syndrome (HNPCC). This syndrome is characterized by an 80% lifetime risk for colorectal cancer, a 60% lifetime risk for endometrial cancer, a 20% risk for stomach cancer and a 12% lifetime risk for ovarian cancer, as well as other cancers. HNPCC is inherited in an autosomal dominant fashion. Colon cancer due to HNPCC is usually not associated with the presence of thousands of polyps. Rather, if a colon cancer is associated with numerous polyps, then it is likely to be caused by an autosomal dominant APC gene mutation, which causes Familial adenomatous polyposis (FAP) or two recessive MYH mutations, which causes MYH associated adenomatous polyposis (MAP).

For any of syndromes listed above, those who are found to have a germline mutation/s prior to cancer diagnosis are eligible to have prophylactic surgery or enhanced cancer screening to modify their risk. For those individuals who are found to have a germline gene mutation after a cancer diagnosis, enhanced screening and/or prophylactic surgery will still be important as they will still be at an elevated risk for future cancers in any susceptible tissue. Additionally, when an individual is determined to have an inherited gene mutation causing an increased risk for cancer, all of this individual's biological relatives can be tested to see if they carry the same gene mutation. Those who do not carry the inherited gene mutation can have peace of mind and can pursue cancer screening as though they are at population risk. It is important to note that not all cancers have effective cancer screening and that prophylactic surgery is only an option for some at risk organs.

A 38 yr old woman comes to you because she is worried about her risk for cancer. Her sister was just diagnosed with ovarian cancer at age 56. There is no history of cancer on her mother's side. Her father died at age 80 from colon cancer. He only had one sibling- a sister. This paternal aunt had endometrial cancer at age 92. His mother-your patient's grandmother, had breast cancer at age 35.

  1. Which genes, if any, should this family be tested for?
  2. Who in this family is the ideal person to order a genetic test on?
  3. Which of the cancers listed above have effective cancer screening?
  4. For which syndromes listed above can you offer prophylactic surgery?