The landmark Human Genome Project is celebrating its 20th anniversary. In 2003, scientists produced a genome sequence that accounted for 90% of the human genome. Two decades later, the project achieved the first complete, gapless sequence of a human genome.
Identifying all disease-causing genes, including those that lead to cancer, is an ongoing goal for the project.
Baptist Health South Florida has been working to make education on DNA and cancer disposition available to patients. In an educational talk, Arelis Mártir-Negrόn, MD, discussed the role of genetic change in cancer and how technology has evolved since the Human Genome Project.
DNA discovery has been instrumental in understanding health and disease and developing therapies. But there are many things that scientists don’t know about DNA.
“I always tell my patients this is still a new science,” said Mártir-Negrόn. She’s the medical director of clinical genetics at Baptist Health South Florida’s Miami Cancer Institute.
Baptist Health South Florida is a member of the AMA Health System Program, which provides additional enterprise solutions to equip leadership, physicians and care teams with resources to help drive the future of medicine.
Variants lead to pathogenicity
DNA has been described as the molecular blueprint of a living thing. Its unique structure allows it to carry information in the sequence of its nucleotides or bases, and replicate, said Dr. Mártir-Negrόn.
Changes or variants can take place in the DNA or chromosome structure, which lead to pathogenicity.
“All cancer is associated to a genetic change in genes that control the way cells grow and multiply,” said Dr. Mártir-Negrόn.
Genes are one of four factors that impact personal risk of cancer, along with lifestyle, environment and family history.
“All cancer is genetic, but not all cancer is hereditary,” said Dr. Mártir-Negrόn. Most cancer is somatic, meaning it happens by chance, although some cases arise from inherited or germline mutations.
Somatic cases could be attributed to environmental factors, or genes yet to be discovered, she said.
These are among the factors pose red flags for genetic cancer risk disposition:
- Diagnosis at or under age 50.
- Multiple primary cancers in an individual.
- Rare cancers.
- Multiple close family members with cancer in the same family lineage.
- Specific combinations of cancer in the family.
Specific genes are associated with certain cancers. Because BRCA is associated with ovarian cancer, “we recommend removing the ovaries because there’s no good screening for ovarian cancer,” explained Dr. Mártir-Negrόn.
Benefits, limitations of tests
A genetic predisposition doesn’t mean a person will get cancer. It means they have an increased risk in comparison to the general population. It also means a care plan might change, such as increased screening.
But if a mutation is in a patient’s genes, there’s a 50% chance they’ll pass it on to their children.
Today, patients can get screened for a hereditary predisposition to cancer using multigene panels and next-generation DNA sequencing.
Genetic testing results can educate a person or family about cancer risk, as well as assist with surgical and treatment decisions. It may also inform an at-risk patient to remove a breast that’s unaffected, for example.
“Genetic testing is way faster now,” said Dr. Mártir-Negrόn. Results that used to take three months are sometimes available in less than 10 days.
Testing also has limitations. It doesn’t necessarily erase family and population risk, the results aren’t always a clearcut “yes or no” answer, and patients can suffer anxiety from testing.
The American College of Medical Genetics classifies genetic results into three categories:
- Positive (pathogenic or likely pathogenic).
- Negative (benign or likely benign).
- Variant of uncertain significance or VUS.
In the last case, “we don’t know if the change is expected to cause problems,” Dr. Mártir-Negrόn said. The good news about VUS is further study usually reveals a benign change, she added.
The same medications and treatments are not universally effective for every patient. Fortunately, simple genetic tests now allow physicians to predict how a patient will respond to many of the most commonly prescribed medicines. Learn more with the AMA about this emerging field of medicine, called pharmacogenomics.
