Why do Genetic Testing?

What is a Gene mutation? We have 23  (22 autosomal pairs of genes + 1 X/Y pair), and carry 2 copies of each gene, one inherited from each parent, for each pair.  Genes determine form and function, and each characteristic can require 2 functional genes, or only one. When one faulty copy is enough to cause a disease, that is a dominant mutation.  When both copies are needed to be faulty to cause a disease, it is a recessive mutation.  With dominant inherited mutations, the pathway to cancer if faster.  If there is no inherited gene mutation, such changes have to occur by chance.

When we take a history from a newly diagnosed patient, we ask for a family tree of Cancer Diagnoses.  Often, we get an answer that “Cancer runs in my family”.  In that case, we do try to map out a family tree, marking who got what kind of cancer, and at what age, and what the outcome was. Certain patterns can emerge, like early age of diagnosis, multiple cancers within the same person, the same cancers in most 1^st degree relatives.  These point to inherited genetic abnormalities. E.g.

-BRCA 1 and 2 mutations, which confer an increased risk of ovarian and/ or breast cancer.

-Lynch syndrome, which is caused by a dominant mutation in DNA mismatch repair genes, which causes an increased incidence mainly of colon and uterus cancers.

-Li-Fraumeni syndrome with a dominant mutation in p53 (a tumor suppressor gene on chromosome 17). One bad copy inherited from a parent causes high rates of early breast cancer, sarcoma, brain and adrenal gland cancers.

Why test? The decision to test should be made after a thoughtful discussion regarding the ramifications of such testing. The US law now protects against discrimination in the event that you test positive for a cancer causing mutation. The knowledge that family members who do not yet have the disease, but carry the mutation can enable them to decide to undertake preventive surgery, e.g. removal and reconstruction of breasts, removal of ovaries, regular screening colonoscopy at an earlier age, etc.

Often, even if cancer runs in your family, we have not yet identified the gene mutation that may predispose to that cancer, and cannot detect it.

Non genetic reasons can also cause cancer to cluster in families: where we live, the occupations we pursue, the foods we eat, and whether we exercise, smoke or drink alcohol in excess. We do not have much control over some of these factors. We live and grow up where we do, and pursue occupations that are available to us. But we can work at improving our environmental conditions by decreasing pollution. We can improve our personal habits by not smoking, and exercising and eating and drinking in moderation. These changes have a direct and measurable impact on our cancer risk, independent of genetic mutations.

The other kind of genetic mutation testing takes place after cancer diagnosis. The DNA of the cancer cell is tested for specific mutations that have drugs designed to work against them. These drugs attack only the intended target, and have minimal impact on the rest of the body’s cells, sparing patients the toxicity of chemotherapy. However, they only work against the targeted mutation, and would not be effective without it.  This way of treating cancer is gaining ground with more targets for more designer drugs being developed. In the coming decades, our current way of choosing chemotherapy may seem very primitive.