Inherited Cancers

When a child is conceived, the baby might inherit a gene with a cancer-causing variant from a parent. If this happens, it increases the child’s risk of cancer. Signs that a cancer is inherited include: 

  • Developing cancer at a young age
  • Having several blood-related family members with similar or related cancers 
  • Having multiple primary (separate) cancers
  • Having rare cancers in a family 

At the Clinical Genetics and Genetic Counseling Service at Fred Hutch Cancer Center, our cancer geneticists and licensed, board-certified genetic counselors specialize in cancer genetics, including inherited cases of cancer. This expertise allows them to offer the best care to patients who have an inherited cancer risk. 

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Understanding Gene Variants

Cells divide to make copies of themselves, and when this happens, all the genes inside are copied, too. This process isn’t perfect, though. Sometimes random errors, called genetic variants, happen. The body can usually fix these errors, but sometimes one isn’t caught and can continue to copy itself and eventually cause problems. 

When this happens, it means this new cell has a genetic variant that is permanent, and this gene variant gets copied into new cells when that cell makes a copy of itself. Usually, these genetic variants are harmless. But occasionally, one variant may prevent a gene from doing what it is supposed to do. These are called pathogenic variants or disease-causing mutations.

When these pathogenic variants are in a parent’s egg or sperm, the parent can pass it down to their children. In this example, the family has a hereditary cancer syndrome. But if these pathogenic variants happen when someone is older and are in a body part that is not the egg or sperm (for example, in the breast tissue), then the person has a somatic gene variant. In this example, the somatic gene variant caused the person’s breast cancer, but their biological children are not at risk of inheriting it from them.

Hereditary Cancer Syndromes

Breast and Ovarian Cancers

There are several hereditary (inherited) cancer syndromes that include breast cancer. 

Hereditary Breast and Ovarian Cancer Syndrome (HBOC)

People with HBOC have a greater risk of developing certain cancers, especially breast cancer (in both men and women). In women, there is also a greater risk of ovarian cancer, and in men, prostate cancer. Pancreatic cancer may be a risk as well. People with this syndrome often develop cancer before the age of 50.  

Peutz-Jeghers Syndrome (PJS)

People with this disease develop polyps and dark-colored spots that can appear on different parts of the body. People with PJS are at greater risk of some types of cancer. 

Li-Fraumeni Syndrome (LFS)

This condition makes a person more likely to develop certain cancers, including cancers of the bone, brain, breast, blood, adrenal gland and muscle or connective tissues. 

Cowden Syndrome (CS)

People with CS are at increased risk of developing certain cancers, including breast, thyroid, endometrial (lining of the uterus) and kidney cancer. Often, they also have macrocephaly (larger-than-average head size), skin abnormalities and colorectal polyps. 

Neurofibromatosis 1 (NF1)

People with this condition develop tumors in their brain, spinal cord and nerves. Usually, NF1 is noncancerous.  

People who carry a disease-causing variant in BRCA1 or BRCA2 (for BReast CAncer1 and BReast CAncer2) have an increased risk of developing breast and ovarian cancer. Children of a person with a BRCA1 or BRCA2 gene variant have a 50 percent chance of inheriting it at conception. Other genes, such as TP53 and PALB2, also increase the risk of cancer when a disease-causing variant is present.  

In 1994, the first gene associated with breast cancer, BRCA1, was identified on chromosome 17 by Mary-Claire King, PhD, a genetics and medicine professor and world-renowned researcher at Fred Hutch’s partner, UW Medicine. A year later, BRCA2 was discovered on chromosome 13.  

Risk Assessment and Genetic Testing for Breast and Ovarian Cancers

Cancer risk assessment that includes genetic counseling and testing is available for hereditary breast and ovarian cancers at the Clinical Genetics and Genetic Counseling Service at Fred Hutch. If you have already had genetic testing and are found to be at high risk, our multidisciplinary experts at Fred Hutch’s Breast and Ovarian Cancer Prevention Program can provide personalized cancer screening and a prevention plan. For more information, call 206.606.6100. 

Prostate Cancer

More than one in 10 men with advanced prostate cancer carry inherited genes that increase their risk for faster-growing forms of the disease that are more likely to spread. Knowing whether a man carries one of these genes may help his physician more precisely tailor his prostate cancer treatment.

Genetic Counseling for Prostate Cancer

People diagnosed with advanced prostate cancer may want to consider a consultation at Fred Hutch's Prostate Cancer Genetics Clinic. For people who don’t have active cancer but have a strong family history of prostate cancer, cancer risk assessment that includes genetic counseling and testing is available at the Clinical Genetics and Genetic Counseling Service at Fred Hutch.

Colorectal Cancer

There are several hereditary cancer syndromes that include colorectal cancer:

Familial adenomatous polyposis

People with FAP develop hundreds to thousands of precancerous polyps. Unless the polyps or colon are removed, they will develop into colon cancer. These people are also at increased risk of developing other non-colon cancers.

Familial colorectal cancer type X (FCCTX)

Families with familial colorectal cancer type X appear to have increased risk only for colorectal cancer. Researchers have not yet found an association with a higher risk of developing other cancers.

Lynch syndrome

People with Lynch syndrome have an increased lifetime risk of developing colorectal cancer. However, they do not develop many precancerous colon polyps. Those with Lynch syndrome have a higher risk of developing endometrial cancer and ovarian cancer, too. Lynch syndrome is also known as hereditary non-polyposis colorectal cancer (HNPCC).

MYH-associated polyposis (MAP)

MAP is thought to have similar cancer risks to FAP, but it is not as well understood as other genes. More research needs to be done to fully understand the risks associated with this syndrome.

Genetic Testing and Risk Assessment for Colorectal Cancers

Genetic counseling and testing is available at the Clinical Genetics and Genetic Counseling Service at Fred Hutch. 

Individuals with increased risk of developing colorectal, pancreatic, prostate and other gastrointestinal cancers can make an appointment at the Fred Hutch Gastrointestinal Cancer Prevention Program. Their care team may include a gastroenterologist, medical oncologist, genetic counselor, registered dietitian and social worker.

Pancreatic Cancer

Pancreatic cancer may be associated with several hereditary cancer syndromes:

Hereditary breast and ovarian cancer syndrome

People with HBOC have a greater risk of developing certain cancers, especially breast cancer (in both men and women). In women, there is also a greater risk of ovarian cancer, and in men, prostate cancer. Pancreatic cancer may be a risk as well. People with this syndrome often develop cancer before the age of 50. 

Peutz-Jeghers syndrome

People with this disease develop polyps and dark-colored spots that can appear on different parts of the body. People with PJS are at greater risk for some types of cancer.

Familial atypical multiple mole melanoma syndrome

People with this syndrome have many moles, and some are abnormal. They are typically noncancerous, but they increase the risk of developing melanoma as well as pancreatic cancer. 

Hereditary chronic pancreatitis

This syndrome causes the pancreas to become inflamed. This inflammation causes damage over time and increases the risk of a person developing pancreatic cancer.

Lynch syndrome

People with Lynch syndrome have an increased lifetime risk of developing colorectal cancer. However, they do not develop many precancerous colon polyps. Those with Lynch syndrome have a higher risk of developing endometrial cancer and ovarian cancer, too. Lynch syndrome is also known as hereditary non-polyposis colorectal cancer (HNPCC).

Genetic Testing and Risk Assessment for Pancreatic Cancer

Genetic counseling and testing for hereditary pancreatic cancer is available at the Clinical Genetics and Genetic Counseling Service at Fred Hutch. 

Teri Brentnall, MD, is a gastroenterologist and researcher. She works with families who have pancreatic cancer to identify the genes that cause hereditary pancreatic cancer not associated with the conditions listed above. People with increased risk of developing pancreatic cancer can meet with Dr. Brentnall and her team at Fred Hutch’s Gastrointestinal Cancer Prevention Program to develop a pancreatic cancer screening and prevention plan.

Melanoma

Hereditary melanoma is linked to many cancerous and noncancerous skin growths, as well as pancreatic cancer. People with fair (light) 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 found a link between inherited and acquired genetic factors that increase a person’s chance of developing a very common type of melanoma. Certain changes in the MC1R gene can give people a much higher genetic risk of developing this type of melanoma, even if they have not had excessive sun exposure and variable pigmentation.

Genetic Testing and Risk Assessment for Hereditary Melanoma

Genetic counseling and genetic testing is available for hereditary melanoma at the Clinical Genetics and Genetic Counseling Service at Fred Hutch.

Leukemia and Blood Disorders

Patients who are at risk for leukemia or a blood disorder fit one of the following criteria:

  • Have a personal or family history of long-standing blood count abnormalities of an unknown cause.
  • Have a personal history of a blood cancer with close relative(s) who also have blood cancers.
  • Were diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) before the age of 45.
    • MDS: Disorders that develop when blood cell production is disrupted.
    • AML: A type of cancer caused by abnormal blood cells forming in the bone marrow.
  • Have a known family history of low white blood counts, inherited bone marrow failure syndrome (IBMFS) or an inherited risk of a blood disease such as:
    • Familial platelet disorder (FPD) with propensity to myeloid malignancies, such as RUNX1 disease-causing variants
    • Familial MDS/AML, such as GATA2 disease-causing variants
    • Telomere biology disorder or another IBMFS, such as Diamond Blackfan anemia or Shwachman Diamond syndrome
    • Another known inherited MDS/acute leukemia predisposition syndrome, such as disease-causing variants in ETV6 and DDX41 genes

Genetic Testing and Risk Assessment for Hereditary Leukemia or Blood Disorders

Fred Hutch is one of only a few cancer centers in the nation to offer a Hematologic Malignancy Genetics Clinic. This program provides personalized risk assessment and follow-up care for adult patients and family members who may be at increased risk of developing hematologic malignancies due to an underlying genetic cause. Patients who come to us have been referred to our clinic for evaluation by their primary care physician. To schedule an appointment, call 855.557.0555.