Question about family genetics and pancreatic cancer

Genetic counselors are trained to answer these sorts of questions, but here's my answer.

One possibility is that your partner's father and grandfather carry(ed) an inherited mutation that increased their risk of developing pancreatic cancer. There are still mutations like this that have not been characterized by scientists, and so are not reported by the current genetic tests. If this is the case, then there is a 50 percent chance that your partner also carries the mutation. So frequent screening is a good idea. It is also possible that the fact that the father and grandfather both had pancreatic cancer is a coincidence, in which case your partner would not have an increased risk.

My family has a similar problem with a different type of cancer (strong family history, but no known cancer-associated mutation in the one living affected individual-me). I wish I could identify the mutation so that my other relative could gauge their risk. I had my whole genome sequenced, but there's too much information to figure out what to do with it (and I'm a professional molecular biologist.)

@lightandhope ,

Your partner should definitely seek out a genetic counselor and have a "germline" DNA test for inherited mutations. There are several (known) mutations associated with a higher chance of developing pancreatic cancer and possibly more unknown, but a family history like that is reason for concern.

FWIW, my paternal grandfather had a digestive cancer (not sure which organ), and my paternal grandmother had breast cancer. We didn't know anything about their genetic status, but we do know my dad (RIP, mesothelioma), a sibling, and I all have mutated versions of the ATM gene, which is a risk factor for breast and digestive cancers. I have pancreatic cancer and my sibling is closely monitoring a pancreatic cyst.

There are some fairly standardized screening guidelines (a few searchable in this forum), based on patient age, number of immediate relatives with cancers, the age at which the relatives were diagnosed, and genetic mutation status (which you'll know after a test). These categorize a patient as normal, elevated, or high risk, and good doctors will take a patient with this information and happily start the appropriate screening process.

Update: There are several searchable discussions for the keyword "Fukuoka" Guidelines related to screening and monitoring pancreatic cysts, and also to MD Anderson's recommendations for PC screening. Link to that one is here: https://connect.mayoclinic.org/discussion/monitoring-a-pancreatic-cyst/?pg=3#comment-990548

Thank you so much for your response! I really appreciate it! I agree that there are probably unidentified gene mutations for this cancer. I hope it's a coincidence. Unlike his dad, my partner has never smoked, very light social drinker, vegan, and is not diabetic. So, I hope some of this reduces his risk.

My follow-up is that are these early once in 2 years scans effective in detecting pancreatic cancer? Not that I am skeptical but want to see some data if available. I was trying to find articles on the outcome of those who are at high risk of pancreatic cancer but had started scans early, but couldn't find any.

Thanks again!

Thank you so much for the resource! I appreciate it!! My partner and his dad did the gene tests but neither appear to have the known gene mutations for this cancer. But, I'll check with him again.

I have another question as you mentioned your sister's cyst. Do these cysts turn cancerous? What does closely monitoring mean- annually or once every 6 mos?

Thank you so much!

@lightandhope , the answer to almost everything is, "It depends." 😉

If a tumor starts to grow right after a scan, then you might go 2 full years before another scan, and it could get out of control quickly. But you might also get lucky with timing and catch the tumor on a scan just as it's coming into existence and have almost a 2-year head start on treating it.

Per those MD Anderson guidelines ( https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/screening/screening-pancreatic-web-algorithm.pdf ), with two or more relatives on the same side of the family having PC, screening would be done every 12 months instead of 24, so that's a benefit.

Screening includes a CA19-9 blood test, which can be done very inexpensively ($25-$50 at some walk-in labs, depending on the state and lab access laws). It's not considered a diagnostic by itself, but a rising trend is reason enough to investigate further. I encourage people at risk to get the test done while healthy, so they'll know their own normal and have a baseline to compare against. It's good to repeat the test a few times (say, once per month for 3 months) so you can see if the data is noisy (all over the place) or pretty consistent. Then spread the tests out further if no significant elevations occur. If rising trends do occur, then get it checked out as quickly as possible by a professional.

Of the many caveats, there are other conditions (serious and benign) that can cause elevated CA19-9, and there are some people with pancreatic cancer who simply don't produce CA19-9. You're always playing the odds, but if you have no symptoms, the odds lean toward the numbers being meaningful.

The cysts can definitely turn cancerous over time, but with guidelines being based on initial scan data, cyst size, and other factors, they have a pretty good set of guidelines for monitoring.

I think my sibling is getting one scan or another every 4 months or so (alternating EUS, CT, MRI, etc) thanks to good insurance and a pretty aggressive, proactive doctor.

Thank you so much for all of the detailed information!! I immensely appreciate it. My partner is just shy of 40. His dad got dx at 70. So, per the MDA guidelines table, it appears that the age recommended to start screening would be 50 for him. Am I reading it correctly? Hopefully by the time he turns 50, it will become an annual screening for him and until then nothing happens.🤞

He hasn't mentioned about the bloodwork. I'll bring it up for him. His dad is the oldest in the family and has younger siblings. Their outcomes are also of interest. I hope everyone remains unaffected!

@lightandhope , You're very welcome. Two other thoughts/angles I forgot to mention:

1) CEA is another tumor marker similar to CA19-9, but perhaps more applicable (associated with more types of cancer). It is also not a single diagnostic indicator of anything, but as with CA19-9, if you start recording it while healthy, you'll know your normal levels and be better able to recognize if it starts trending above normal. It's a cheap and easy test within the range of self-pay if necessary. For tests like this, it's important to get them done at the same lab for consistency. There can be substantial variation between labs and their tests.

2) There is a "multi-cancer panel" blood test from Grail, called "Galleri." It's supposed to provide early detection of up to 50 different types of cancer. It costs about $1000 and is not FDA approved, so it would definitely be a self-pay. All the usual caveats about sensitivity, specificity, false negatives and false positives (and your response to them) apply. But it is an easily accessible, non-invasive test. Almost any doctor can order it for you, or you can speak with one of Grail's counselors by phone and get it approved.

I was disappointed -- got a false negative from Galleri on my PC recurrence, but that was accompanied by false negatives on Signatera (DNA) test and EUS biopsy as well. MRI and rising CA19-9 were the only reliable indicators of recurrence, although as I've mentioned, I think a PET scan could have confirmed the MRI and CA19-9 results to confirm recurrence of my cancer earlier. PC can be really hard to detect!

In summary, if you're not looking for PC, you might not find it until too late. If you're looking, it improves your overall chances. If you get false negatives, at least you tried your best. But remember that "absence of evidence is not evidence of absence." If you get false positives, it does call for prioritizing further investigation, but not necessarily overreacting. For example, an immediate biopsy after one positive test result might be excessive, invasive, and dangerous. See if the test can be repeated (same and/or different lab) or if a different, non-invasive test can verify the first result before resorting to something surgical or otherwise invasive/dangerous.

And as for the screening guidelines, I read it as you did that screening for your partner would begin at age 50, but that doesn't mean a doctor can't start earlier, which I would definitely do given the family history.

If you can't get doctors/insurers to go along with all the official screening guidelines (i.e., imaging can be expensive), you can still start with PCP or self-referral and self-pay for the basic blood tests. Educate yourself about all the symptoms to watch for and be ready to react quickly if they occur. Adult-onset diabetes, unexplained weight loss, jaundice, changes in stool and urine, digestive issues, and mid-back pain are among many others to be aware of. In my case, the first true red flag was high liver enzymes caused by the tumor blocking my common bile duct. In hindsight, I think my fingernails chipping more than usual might have been an even earlier indicator, suggestive of not properly absorbing nutrition from my food.

Know your body!

Thank you so much again for the informative post. Unfortunately my partner's dad passed away recently after almost 3 years post PC dx. We will be on top of this even though my is partner young- just shy of 40. I like your suggestion on having baseline bloodwork numbers as early as possible. He already has started getting imaging of pancreas done once every two years.

While I see a lot of info on the outcomes of typical late stage detection of PC that contributes to its viciousness, I don't see much info on outcomes of those at high-risk who started surveillance earlier with no evidence of disease and with no symptoms, like my partner, due to reasons such as genetic markers, fam history and such.

Hi val64,
Did you have surgery? If so, did they run the testing on your tumor tissue? This will also show mutations that could have been inherited. That was the case for me.

I did have the tumor sequenced, and the germline "variants of uncertain significance" that were reported were all derived from the wrong parent. (I not only had my whole genome sequenced, but also that of my one living parent. So I could tell who germline variants came from.). Good idea, but it didn't work for me.