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Who Gives a Spit? Should You?
Navigating the confusing world of genetic testing in prostate cancer, with help from PCF Young Investigator Saud AlDubayan, M.D., a Harvard clinical geneticist.

What’ll you have?  Eggs?  Fried, over easy, scrambled, boiled or poached?  Potatoes?  Hash browns or steak fries?  Coffee?  Regular or decaf?  Do you want cream, half-and-half, 2 percent, skim milk, almond milk, coconut milk, or soy milk?

And that’s just breakfast!  Every day, most of us are bombarded with choices.  Add illness into the mix, and making decisions can be overwhelming.

Which brings us to genetic testing in prostate cancer.

Maybe you thought the world of prostate cancer treatment was already confusing enough.  Wrong!  You might find it even more confusing, because there’s a whole new category to consider:  genetic testing.  Do you need it?  If you do, should you get a blood test or a spit (saliva) test?  Will getting this test help your family?  Could it hurt your family’s ability to get insurance?

Don’t despair!  Help is here!  Physician-scientist Saud AlDubayan, M.D., of Harvard Medical School, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, and the Broad Institute of MIT and Harvard, is a clinical geneticist and computational biologist, and the recipient of a PCF Young Investigator Award.  His expertise is on the germline, or inherited, genetic defects that predispose to prostate cancer and other cancers, as well.  He uses “computational and epidemiological approaches” – doing sophisticated analyses using computers to sift through massive amounts of genetic information – to discover new genes and pathways involved in the development of prostate cancer.  He also sees patients with “strong family histories of cancer, or strong personal histories of various types of cancer – unusual, not straightforward cases.”  In short, he is an expert on germline genomics: making sense of the genetic alterations we are born with that could cause serious illness.

Here are his answers to some of the most frequently asked questions about genetic testing in prostate cancer:

Do all prostate cancer patients need genetic testing?

No; there is not yet sufficient evidence to support that, but AlDubayan hopes to have much more specific guidelines soon.  “Many scientific groups are working to identify subsets of patients where genetic testing is clearly indicated,” but for now, nobody is saying that germline genetic testing will help every single man diagnosed with prostate cancer – especially men with low-risk, small-volume cancer that may never need to be treated.

So, who should get a germline genetic test?   You should, if:   

You have metastatic prostate cancer.  In a recent multi-center study, AlDubayan and colleagues from six major cancer centers in the U.S. and U.K. studied the inherited genetic alterations of approximately 700 men with advanced prostate cancer.  “All 700 men had metastatic disease, and of these, 12 percent were found to have one or more germline genetic alterations that affect the patient’s ability to rebuild DNA.”  If you turn out to have an alteration in a DNA-repair gene, such as BRCA1 or BRCA2, this could make a difference in how your cancer is treated.  “Now we know that if you have a germline alteration in one of these genes, you could qualify for alternative treatment,” such as platinum chemotherapy or a PARP inhibitor (a drug such as olaparib).  “The silver lining to having one of these mutations is that you respond well to certain types of treatments.”

You are diagnosed with prostate cancer before age 50.  “If you develop prostate cancer and you are 50 years of age or younger, you have a higher chance of carrying a genetic alteration predisposing to prostate cancer and potentially other cancers as well.” says AlDubayan.

You have prostate cancer and you have a family history of prostate cancer.  “If you have either two or more first-degree male relatives already diagnosed with prostate cancer, regardless of their age, and you are the third, then genetic testing would probably be beneficial,” says AlDubayan.  “Or, if you have prostate cancer, and you have a brother, father, or uncle who developed prostate cancer at a younger age, before age 60, germline testing might be beneficial, as well.”

You have prostate cancer and you have a family history of other kinds of cancers.  “Prostate cancer can be one manifestation of a cancer predisposition genetic syndrome,” says AlDubayan.  “Maybe you have one family member who has had colorectal cancer, or your sister has had breast or ovarian cancer.  This could indicate a broad genetic syndrome that makes you more likely to get prostate cancer – but you could also be at risk of getting cancer in other organs,” and this means you need to be checked more frequently for other types of cancer.  Although it’s not clear how many relatives with cancer it takes to be considered a “high-risk cancer family,” AlDubayan believes “if you have a sister with breast or ovarian cancer, especially if she developed it before age 50, you need to be evaluated for germline genetic testing.”

What if you don’t have prostate cancer?  Should you get a germline genetic test?

“This is guided mostly by the family history.  If you have a family history of prostate cancer, or other cancers, or if you have a known genetic mutation in the family, you need to know if you are genetically at higher risk, as well,” says AlDubayan.    Note:  If cancer runs in your family, it is not a done deal that you have inherited the “bad” gene alteration.  “Say a man develops metastatic prostate cancer, or develops it before age 50, and he has a brother.  Clearly, the brother qualifies for germline genetic testing; there’s a 50 percent chance he shares the same genetic alteration.  But it makes more sense to test the affected individual – the brother who actually has cancer – first.  And then start testing the family, starting with the siblings and the children, then the second- and third-degree family members,” such as grandchildren and cousins.   Note:  even if you have a mutated gene, this doesn’t mean you will get cancer!  But it does raise your risk, and knowing this, your doctor may want to start screening you for cancer earlier, or more frequently.

What kind of test is better?  Blood or spit (saliva)?

“Either should be fine,” says AlDubayan.  “With advancements in next-generation sequencing, saliva tests are comparable to blood tests.  At our clinic, if patients can give blood, we take blood, or if they send a saliva test, we’ll take that.  It’s guided by the convenience of the patient.  Most major clinical labs accept saliva or blood.”

Note those words: “major clinical labs.”  AlDubayan is talking about clinical testing, set up through your doctor’s office, done at a medical center or reputable lab.

So, what about 23 and Me?  Make sure you know what you’re getting.  What this and some other companies offer, AlDubayan says, is “selected testing.  They do not examine all of the cancer risk genes, or even all parts of the commonly tested genes.  They typically just examine the most commonly affected sites.  So if you have a negative result, it doesn’t mean you’re actually negative,” that you don’t have a mutation that could lead to cancer.  “It just means they didn’t find it in these selected sites.  You may read it as negative, but it may just mean you don’t have one of the common mutations in BRCA1 and BRCA2” or another well-studied gene.

Clinical testing, on the other hand, is more comprehensive.  “When we test a gene, we test the whole gene – every single coding piece of the gene.”  Also, “genetic testing is not limited to BRCA1 and BRCA2; usually we extend it to many other DNA repair genes, even though their association with prostate cancer risk hasn’t been delineated robustly, because we think these genes are in the same pathway.”

What about Color Genomics?  “This test looks at 30 genes,” and according to its website, it offers “free one-on-one phone calls with a genetic counselor to get answers.”  AlDubayan believes that patients “need to have counseling before and after the test.  They need to understand what the test covers, and what the results mean.  That’s the recommendation of the American College of Medical Genetics (ACMG) – that you get pretest counseling.  Before you get a genetic test, you should have a discussion with a genetic counselor or a clinical geneticist so you can understand what it means:  what genes are tested, what it means to find a positive or negative – or, sometimes there’s a finding of undetermined importance, and we call it a variant of unknown significance.”  You also need to talk to a genetic counselor or someone really familiar with germline genetics after the test, he adds.  “You need someone to explain what the findings were,” and also to explain what to do with these findings.  “You may get specific screening recommendations for other cancers.  If you have siblings, male or female, the counselor may want to talk to them about their risk.  You may need to get genetic testing for the family,” but it’s easier at this point, because your family members will undergo targeted testing.  “You can just test for that particular alteration in every single family member, so everyone can know if they’re a carrier or not.”

HOWEVER, and this is a pretty significant potential can of worms: 

If you get a genetic test ordered by your doctor, it becomes part of your medical record.  Forever.   “You may be discriminated against,” says AlDubayan.  There is some protection against genetic discrimination.  A federal law called the Genetic Information Nondiscrimination Act (GINA), passed a decade ago, prohibits genetic discrimination in health insurance and in employment.  It has two parts: Title I and Title II.  “Title I makes it illegal for health insurance providers to use or require genetic information to make decisions about a person’s insurance eligibility or coverage,” according to the National Institute of Health’s Guide to Understanding Genetic Conditions.  Title II makes it illegal “for employers to use a person’s genetic information when making decisions about hiring, promotion, and several other terms of employment.”  But GINA and other laws do not protect people from genetic discrimination in every circumstance.  For example, GINA “does not apply when an employer has fewer than 15 employees.  It does not cover people in the U.S. military or those receiving health benefits through the Veterans Health Administration or Indian Health Service.  GINA also does not protect against genetic discrimination in forms of insurance other than health insurance – such as life, disability, or long-term care insurance.”

AlDubayan worries about this for his patients, and wants to make sure they understand the potential ramifications.  “If you [the physician] have someone with early-onset prostate cancer, someone in his 40s, you want to do genetic testing – but you also want to make sure he has life or disability insurance before he gets the test.  Once you do the genetic test, it’s part of his permanent medical record.  Insurers will want that information, and can deny him life insurance,” or disability, or long-term care.  “There’s no way to keep it private when it’s done in a clinical setting.”  Similarly, 23 and Me “shares your genetic information with authorities – the raw genetic data.  They give everything.”

Is it possible to order a test privately, and keep the results a secret?  Maybe.  But privacy policies, terms and conditions, and all the legalese on various genetic testing companies’ websites make it difficult to understand just how protected – or not protected – you are. Furthermore, says AlDubayan, “some testing vendors, when indicating that they don’t share patients’ information – they are referring to the raw genetic information.  But they may still share the results of the testing, which is sufficient for insurers to identify mutation carriers as high-risk and treat them accordingly.

Will insurance cover the test?  Again, no universal answers.  “It depends on what kind of insurance you have.  Some are much better than others; there’s absolutely no standard whatsoever.   Some plans may allow you to do broad genetic testing that would cost many thousands of dollars.  Others wouldn’t allow anything, even if it’s a matter of hundreds of dollars.”  Your best bet here is to talk to a clinical geneticist or a genetic counselor.  “We advocate for our patients,” says AlDubayan.  “If there is a clear indication to have genetic testing – if it could enable you to have alternative treatment, for example – the likelihood of its being covered is much higher.  It also depends on the lab,” and on your medical center.  AlDubayan’s Genetics and Genomic Medicine Service at the Brigham and Women’s Hospital, for example, has an agreement with a major commercial clinical lab to cap patients’ out-of-pocket expenses at $250.  “If we can’t get insurance to pay for the test, there is a maximum $250 fee for the patient.”  But if a patient uses a lab that doesn’t have such an agreement with a medical center or doctor’s office, “the patient might get billed for much more.”

To avoid a nasty surprise, it’s essential to find out ahead of time what you might be expected to have to pay.

Another tip:  Ask your doctor for a referral to a genetic counselor, a clinical geneticist or an oncologist with expertise in germline genetic testing.  “Unless you (the physician] are familiar with germline genetics, you can misinterpret or don’t fully appreciate the results.  I have seen non-geneticist physicians freak out because they did not expect a test to be positive; they wanted to rule it out – now the test is back with a germline mutation in a gene they are not familiar with.  Or, if you get ‘variants of unknown significance,’ or rare variants that haven’t been seen in cancer patients or any of the reference databases, what do you do?  We all have normal benign variants; this is why we are different from each other.  If you find a variant that is not known to be disease-causing, is it bad or is it part of normal variation?   That can be really problematic.  The patient can get super anxious and can have emotional distress; the family wants to know.  What do you do?”

Medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the PCF, recommends talking with your doctor about the risks, insurance issues, and any other concerns.  And then:  “If you have metastatic prostate cancer, or if you have been diagnosed with prostate cancer and you have a family history of prostate cancer or other cancer, you should strongly consider germline genetic testing — either blood or saliva.  It could be life-changing for you and your family.”

Janet Worthington
Janet Farrar Worthington is an award-winning science writer and has written and edited numerous health publications and contributed to several other medical books. In addition to writing on medicine, Janet also writes about her family, her former life on a farm in Virginia, her desire to own more chickens, and whichever dog is eyeing the dinner dish.