Genetics

The early detection of cancer is based on the idea that if a cancer is caught at an early stage it can be potentially cured or minimized rather than waiting for it to grow and spread to other areas of the body before detection.  Early detection and screening for cancer is based upon which cancers are most common.  Although angiosarcoma is a deadly cancer, there is no public health screening initiative for it because it is rare and quite difficult to cure.  On the other hand, cancers such as breast, colon and prostate are easier to screen for and often have pre-cancer forms that can be detected and treated in the hopes of preventing an invasive cancer from forming.

The availability, ease and safety of a screening test will make it more or less useful depending on the risk-benefit ratio.  Although pancreatic cancer is a deadly cancer and early surgery is the only hope for cure, there is no easy and cost-effective way to screen for pancreatic cancer.  Furthermore, if a wide part of the population was screened for a particular cancer it would be more likely to detect many “false-positives” or findings that looked like a tumor that really is not cancer.  This creates a conundrum of more unnecessary and potentially harmful testing to chase down a small amount of actual cancers.  The potential harm done from screening tests is not a small issue and causes physicians to consider the risks and benefits carefully before ordering them.

A key link to early cancer detection is a person’s genetics.  There are several ways to consider genetics as a component of early cancer detection.

1)  Strong family risk factors without a specific genetic mutation identified: This is among the most common scenarios that prompt cancer screening or early cancer screening that is different from the nationally established guidelines.  For example, if a woman has several close relatives that get colon cancer at an early age, this may prompt her to get screening for colon cancer done before the age of 50.  There may be no known genetic disease in the family but a very basic knowledge of genetics would say that she is at an increased risk of colon cancer compared with the average person.  There may be a genetic mutation present such as mutation in the APC gene on chromosome 5, which has not been tested for, or no mutation detectable by any extent of testing.

2)  Known genetic syndrome in your family:  This situation is less common but fortunate for the person involved.  If someone is adopted or has little contact with their family, they may not know of a potentially treatable or curable condition that they were born with.  An example of this would be a family history of the BRCA-1 gene mutation.  A woman with this gene has a greatly increased risk for developing breast and ovarian cancer.  If a woman knows that her mother or sisters are carriers of this gene, it would be wise to have testing for this mutation also.  There is a chance that she may not have inherited the gene.  Another example would be an intestinal polyp syndrome (there are several different kinds) that causes many polyps to form and greatly increases the risk of colon cancer.  People with this knowledge can begin screening at an early age or even have a prophylactic surgery done early on as well.

3)  An unusual cancer diagnosis, without any family history of genetic cancer syndrome, that prompts investigation for a  specific genetic syndrome:  An example of this would be a man who is diagnosed with a colon cancer at the age of 30.  This is much younger than the usual age of diagnosis for colon cancer and should prompt consideration of a genetic mutation or syndrome in the family.  The easiest way to check for this is by reviewing the family medical history.  If there are unusual cancers, of similar origin, occurring at young ages this may indicate genetic testing is needed.  The problem is, there are many genetic syndromes that are incompletely characterized and for a particular cancer such as colon cancer there are many possible genetic mutations leading to the same endpoint.  Thus it is possible to not have mutations A, B or C that are tested for, but still have mutation D that causes colon cancer anyways.  There are guidelines that help utilization of these tests in the most efficient manner.

Knowing that a certain cancer runs in your family might also change behavior to limit modifiable risk factors.  For example, if your father and brother both died of lung cancer it would be a very good idea to not smoke cigarettes as you are at a much greater risk of getting lung cancer than the average person.  There is no “genetic test” to prove this but clinical experience and a basic understanding of genetics makes this a common sense recommendation.

There are several drawbacks to genetic testing.  The most obvious is cost and efficiency.  Genetic testing is expensive and the results are often difficult to interpret.  For example, testing for the BRCA-1 gene is done and is “normal” meaning the person does not have that mutation.  This does NOT mean that the person is then free of the risk of developing breast cancer.  About 90-95% of breast cancers develop in persons without a familial genetic cancer syndrome.  If the test is normal this also means that they still could have another mutation that will lead to early onset breast cancer.  There is not a test for every type of genetic mutation that leads to familial cancer also.

Another conundrum is that the reporting of a genetic test is not like a pregnancy test (i.e. positive or negative).  There are percentages and shades of gray reported also.  What exactly does it mean if you have 75% of a particular mutation?  How should this knowledge change your action for screening or prophylactic screening?  These are difficult questions without clear answers.  This is why genetic testing should be used only after careful discussions with your doctor concerning your specific cancer risk factors.  Only once the benefit and change in decision making based upon potential test results have been fully defined, should genetic testing be undertaken.

REFERENCES:

  1. www.cancer.gov/cancertopics/screening
  2. apps.nccd.cdc.gov/uscs/toptencancers.aspx#All
  3. Carey WD. (2010) Cleveland Clinic: Current Clinical Medicine, 2nd ed. Section 14.  Cleveland, OH: Saunders.
  4. Abeloff, M.D. (2008). Abeloff: Abeloff’sClinical  Oncology, 4th ed. Chapter 26. Philadelphia, PA: Churchill Livingstone – Elsevier
  5. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.