Genetic Mutations and Cancer Risk
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 31, 2015
This article provides an introduction to several of the more common genetic mutations associated with cancer risk and development.
BRCA 1 & 2
The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 gene. If you have inherited a mutated copy of either gene from a parent, you have an estimated 40-85% chance of developing breast cancer during your lifetime. People with these mutations tend develop cancer at a younger age (before age 40) and cancers more often affect both breasts. People with these inherited mutations also have an increased risk for developing other cancers, particularly ovarian cancer, but also male breast cancer, pancreatic cancer, and prostate cancer. BRCA mutations occur more commonly in individuals of Ashkenazi Jewish (Eastern European) decent, Norwegian, Dutch, and Icelandic populations, but they can occur in any racial or ethnic group.
If you know that you have a BRCA 1 or BRCA2 mutation, you should talk to a healthcare provider to ensure you receive the proper screening or treatment (chemoprevention) to reduce the chance of developing cancer or to detect cancer at an earlier stage when treatment is most effective. Your healthcare provider may recommend getting mammograms at a younger age, special breast and/or ovarian cancer screening tests, or other interventions, such as, prophylactic (preventative) surgery or chemoprevention.
Hereditary Non-Polyposis Colon Cancer (HNPCC)
HNPCC, also known as Lynch syndrome, is caused by an inherited mutation in any one of several genes that help to repair DNA damage. About 3 to 5 % of all colorectal cancers occur in people with HNPCC, with most of these cancers occurring before the age of 50. The lifetime risk of colorectal is estimated to be as high as 80% in people with HNPCC.
People with HNPCC may develop polyps at the same rate as others, but these polyps are more likely to become cancer and in a shorter period of time. It is important that people with HNPCC begin having colonoscopies at age 20-25 and that colonoscopy is repeated every 1-2 years because cancer can occur so early and quickly in this population.
Women with HNPCC also have a very high risk of developing cancer of the endometrium (lining of the uterus). The estimated lifetime risk for endometrial cancer in these women is 40-60% and the average age at diagnosis is 50 years old. It is recommended that women with HNPCC have an annual transvaginal ultrasound or endometrial biopsy starting at age 25-35. Other cancers linked with HNPCC include cancer of the breast, ovary, stomach, small bowel, pancreas, kidney, brain, ureters (tubes that carry urine from the kidneys to the bladder), and bile duct.
Familial Adenomatous Polyposis (FAP)
FAP is caused by a mutation in the APC gene, which is most often inherited from a parent. In 30% of cases, however, it occurs without a family history. About 1% of all colorectal cancers are diagnosed in people with FAP. People with FAP typically develop hundreds or thousands of polyps in their colon and rectum, beginning in their teens or early adulthood, some as early as 10 years old. Cancer usually develops in 1 or more of these polyps as early as age 20. By age 40, almost all people with FAP will have developed colorectal cancer if preventive colectomy (surgery to remove the colon) is not done. For this reason, most physicians recommend colectomy at a young age for cancer prevention in individuals with FAP. Several other cancers are associated with FAP, including periampullary (where the bile duct and pancreas empty into small intestine) and thyroid cancer.