Cancer Genetics

Is cancer genetic?

All cancer is genetic in one sense: cancer means that cells in the body have acquired mutations and are growing out of control. Although cancer itself is never inherited, genetic factors that increase susceptibility to developing cancer may be inherited. Most cancer, however, is considered “sporadic” — not familial or hereditary. Age, environmental factors, and random chance all contribute to the development of sporadic cancer.

When cancer is diagnosed at younger ages than is typical, or when there are multiple cancer diagnoses in a family that fit a certain pattern, it can be reasonable to consider the possibility of an inherited susceptibility to developing one or more specific types of cancer.

Why does family history matter?

Both inherited genetic and environmental factors may contribute to the risk of developing cancer. Environmental factors are often shared within families. Familial genetic risk factors may be spread out over hundreds of genes. The risk conferred by these genes individually may be minor. Taken together, however, the risk conferred may be significant.

Risk conferred by a number of different genes is often best appreciated when looking at a family history of cancer rather than actually analyzing genes. This is one reason why knowing your family history of cancer and sharing the information with your healthcare provider can be important in guiding your personalized plan of care — even in the absence of genetic test results, and even or especially when genetic test results are negative.

Hereditary cancer syndromes

In a minority of cancer cases, a mutation in one specific gene may be identified that confers a high risk of developing one or more specific types of cancer. This mutation in a single gene often helps to explain atypical patterns of cancer that have been seen in an individual or in a family. When significantly increased cancer risks are associated with a mutation in a single gene, the term “hereditary cancer syndrome” is often used.

A positive genetic test result in a gene associated with a recognized hereditary cancer syndrome provides valuable information about an individual’s cancer risks and can be extremely helpful in guiding an individual’s personalized plan of care. Depending on the result, different or increased screenings may be recommended, and in some cases preventative surgeries may be considered to dramatically reduce the chance of developing a cancer.

While there are many different hereditary cancer syndromes, most of them are rare. Only two are relatively common in the general population.

BRCA-Related Cancers

Hereditary breast and ovarian cancer is associated with mutations in the BRCA1 and BRCA2 genes. Mutations in either of these two genes confer a significantly increased risk of developing breast and ovarian cancer, as well as a more modest increase in risks for developing pancreatic, prostate, and skin cancer. About 1 in 200–500 individuals in the general population carry a mutation in one of these two genes.

Within the past few years, clinical testing of other genes associated with a significantly increased risk of breast and/or ovarian cancer has become available. If you previously had genetic testing of the BRCA genes and had a negative result, it would be reasonable to consider additional testing of other associated genes.

Lynch Syndrome

Although Lynch syndrome receives much less public attention than hereditary breast and ovarian cancer, it is just as common, affecting 1 in 200–500 individuals in the general population. Lynch syndrome is caused by mutations in any one of several different genes (MLH1, MSH2, MSH6, PMS2, EPCAM). Individuals with Lynch syndrome have high risks of developing colon and uterine cancers, significantly increased risks for stomach and ovarian cancer, and more modestly increased risks for a number of other cancers.

Genetic testing for Lynch syndrome should be considered when: colon or uterine cancer is diagnosed before age 50 (or even 64); colon cancer diagnosed at any age has specific features found on pathology testing; or three or more family members have cancers associated with Lynch syndrome, especially across two generations.

What does a cancer genetics consultation involve?

A cancer genetic counseling consultation involves review of three to four generations of your family medical history, with a focus on cancer diagnoses. Discussion includes the likelihood that the cancers in your family have a hereditary contribution; if and how genetic testing may help clarify these risks; and differences in genetic testing options.

If, after counseling, you are interested in moving forward with genetic testing, your genetic counselor can order or facilitate testing for you. If you have already had cancer genetic testing done, your counselor will discuss your results as well as whether any further genetic testing may be recommended.