Inherited Causes of Cancer

What is cancer?

Cancer develops when abnormal cells divide and grow unchecked.
Hereditary cancer occurs when a person inherits an altered gene, or gene mutation, from a parent. Only about 5 percent of cancers are caused by a single strong-acting genetic change that is passed in a family. Signs of hereditary cancer include:

Cancer at a young age such as breast cancer in the 30s or colorectal cancer in the 40s.
Several blood-related family members with similar or related cancers, such as breast and ovarian cancer.
Multiple primary (separate) cancers in one individual.
Rare cancers such as breast cancer in a man.

Known Cancer Genes
Below is a short summary of what is known today about some of the most common forms of cancer.

Hereditary Breast Cancer
Prostate Cancer
Colorectal Cancer
Pancreatic Cancer
Melanoma

Hereditary Breast Cancer
There are several well-described hereditary cancer syndromes that include breast cancer:

Hereditary breast and ovarian cancer
Peutz-jeghers syndrome
Li-Fraumeni syndrome
Cowden syndrome

In 1994, the first gene associated with breast cancer - BRCA1 (for BReast CAncer1) was identified on chromosome 17 by Dr. Mary-Claire King, UW genetics and medicine professor and world-renowned researcher. A year later, BRCA2 was discovered on chromosome 13. Women who carry a disease causing alteration in BRCA1 or BRCA2 have an increased risk of developing breast and ovarian cancer. Children of an individual with a BRCA1 or BRCA2 alteration have a 50 percent chance of inheriting the gene alteration. Genetic testing is clinically available for BRCA1 and BRCA2 at UW Medical Center's Medical Genetics Clinic, as well as other hereditary cancer syndromes that include breast cancer.

Individuals with a family history of breast cancer and/or a genetic predisposition to breast cancer would benefit from a consultation in the Breast and Ovarian Cancer Prevention Program to develop and discuss an individualized cancer screening and prevention plan. For more information about making an appointment, call (206) 288-1024.

Prostate Cancer
In 2004, after three and a half years of gene mapping, the Fred Hutchinson Cancer Research Center and University of Washington Medical Center (UWMC) discovered a gene associated with prostate cancer that runs in families which may also trigger an inherited susceptibility to primary brain cancer.

Finding genes such as CAPB (cancer of the prostate and brain) may provide clues that will eventually help diagnose, treat, cure, and even prevent prostate cancer.
The Fred Hutchinson Cancer Research Center is conducting the Prostate Cancer Genetic Research Study (PROGRESS). This nationwide research project is exploring why some families have several male relatives with prostate cancer. You can find more information about this study on the web, or call the study office weekdays between 8:30 a.m. and 4:30 p.m. Pacific time at 1- 800-777- 3035 or send them an email.

FHCRC - The PROGRESS Study
1100 Fairview Avenue North, M4-A402
P.O. Box 19024-1024
Seattle, Washington 98109

Colorectal Cancer
There are several hereditary cancer syndromes that include colorectal cancer:

Familial adenomatous polyposis (FAP)
Hereditary non-polyposis colorectal cancer (HNPCC)
MYH-associated polyposis (MAP)
Familial colorectal cancer X

Genetic testing is available for the first three conditions above. Researchers are currently trying to identify the genes that cause familial colorectal cancer X.

Individuals with FAP will develop hundreds to thousands of pre-cancerous polyps, and unless the polyps or colon are removed, they will inevitably develop colon cancer. These individuals are also at increased risk to develop other non-colon cancers.

MAP is thought to have similar cancer risks as FAP, but is not well described. Individuals with HNPCC do not get very many pre-cancerous colon polyps but they do have up to an 80 percent lifetime risk of developing colorectal cancer.

Men and women with HNPCC have a high lifetime risk of developing colorectal cancer. Women with HNPCC have a significant risk to develop endometrial cancer and ovarian cancer.

Families with familial colorectal cancer X appear to only have increased risk for colorectal cancer, but there does not seem to be an association with a higher risk of developing other cancers.

Genetic counseling and testing is clinically available for the above conditions associated with colorectal and other cancer at UW Medical Center's Medical Genetics Clinic.

Individuals with increased risk to develop colorectal cancer, endometrial cancer, ovarian cancer, and/or other gastrointestinal malignancies can make an appointment at the Gastrointestinal Cancer Prevention Program to meet with a gastroenterologist, genetic counselor, nutritionist, and if indicated, gynecological oncologist.

Pancreatic Cancer
Pancreatic cancer is seen in several hereditary cancer syndromes:

Hereditary breast and ovarian cancer, especially in BRCA2 carriers
Peutz-Jeghers syndrome
Hereditary melanoma
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome

Teri Brentnall, MD, a University of Washington gastroenterologist, professor, and researcher is currently working with several families that have pancreatic cancer to identify the genes that cause hereditary pancreatic cancer not associated with the conditions listed above.

Genetic counseling and clinical genetic testing is available for all of the conditions listed above at the UW Medical Genetics clinic at UW Medical Center. Individuals with increased risk of developing pancreatic cancer can meet with Dr. Brentnall at the Gastrointestinal Cancer Prevention Program to develop a pancreatic cancer screening and prevention plan, by calling 206-288-1024 to make an appointment.

Melanoma
Genetic counseling and clinical genetic testing is available for hereditary melanoma at the UW Medical Genetics clinic. Hereditary melanoma is linked to many malignant and benign skin growths, as well as pancreatic cancer.

People with fair skin are generally at increased risk of developing melanoma. Differences in skin color, or pigmentation, are due largely to the melanocortin-1 receptor (MC1R) gene. Researchers have identified a link between inherited and acquired genetic factors that increase a person's chance of developing a very common type of melanoma expected to be diagnosed in over 62,000 people in the United States in 2006. The MC1R gene dramatically predisposes those with no excessive sun exposure and variable pigmentation to developing this type of melanoma.

December 2006