Genetic evaluations to uncover increased risk for certain cancers have become standard practice for those with a strong personal or family history of cancer, and have led to advances in early detection and prevention.
Endeavor Health oncologist Allison DePersia, MD, who has specialized expertise in genetics and caring for patients at a high risk of developing cancer, explains the role of traditional genetic testing and the potential for applying newer polygenic risk score (PRS) tests, in cancer risk evaluation.
Genetic testing
The cancer risk assessment process usually starts with your primary care physician, who will collect a family history and recommend a referral to genetics if there is a strong personal or family history of cancer, or history of cancer at young ages.
If you and your genetics team decide to pursue a genetic test, a simple blood draw or saliva sample will be used to look for inherited mutations in genes that are associated with higher cancer risks. If a mutation is detected in a gene associated with increased risk of cancer, your physician will share recommended guidelines to screen for and prevent that specific cancer.
For example, hereditary breast and ovarian cancer syndrome (HBOC) is a monogenic disease, or disease caused by a pathogenetic variant, a change in a single gene (either BRCA1 or BRCA2), that is well-known and well-publicized and causes increased risk for breast, ovarian, prostate and pancreatic cancer.
“A positive test that shows a pathogenetic variant such as BRCA1 or BRCA2 will help guide how we screen for cancers,” said Dr. DePersia. “However, you can have a negative genetic test and may still have an increased risk of cancer, if you have a strong family history or personal risk factors.”
There are numerous possible explanations for why a person may have negative genetic testing even though they have a strong personal or family cancer history:
- There may be a genetic mutation that can’t be found on testing because either the gene has not been discovered yet or current technology is not able to detect the mutation.
- Another possibility is that the cancer risk in the family is due to numerous small genetic changes, or single nucleotide polymorphisms (SNPs), in a gene that add up to cause risk, rather than one specific mutation, explained Dr. DePersia.
PRS testing
Some patients with a negative genetic test may choose to undergo PRS testing which analyzes multiple genomic variations. While genetic testing that looks at single mutations is very well-established and has been in use for more than two decades, PRS testing is still evolving as it relates to identifying increased risk and specifically how to use those findings to personalize cancer screening.
The clinical utility in terms of using PRS findings to develop guidelines for cancer screening and prevention is still the subject of much research, explained Dr. DePersia. For patients concerned about breast, ovarian and other cancer risks, PRS testing can add additional information about an individual’s cancer risk, however, there are not yet guidelines for using the data to personalize individual screening or prevention.
“The guidelines and research around PRS are evolving and there’s no doubt, they will play a big role in ongoing efforts to personalize early cancer detection and prevention in the future,” said Dr. DePersia.
Addressing cancer risk factors
“While traditional genetic testing is still our standard of care for identifying individuals at high risk for breast cancer and other cancers, there are also many other factors that contribute to cancer risk. Even with a negative genetic test, increased cancer screening may be recommended, and it’s important that patients make lifestyle changes to reduce their cancer risk,” she said.
Obesity, alcohol consumption and smoking have all been linked to an increased risk of cancer.
“A lot of smaller risks can add up,” added Dr. DePersia. For breast cancer specifically, there are other risk factors that can’t necessarily be modified including breast density, a history of therapeutic chest radiation and endogenous hormone history including age of first childbirth, menarche and menopause.
Any and all risk factors should be taken into account when determining risk and making breast cancer screening recommendations.
The genetic wellness assessment (GWA) available at Endeavor Health hospitals offers a unique opportunity for patients to answer a brief personal and family cancer history questionnaire and access genetic testing to begin identifying genetic risks for cancer and other conditions.
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