Received COLOR GENETIC TEST RESULTS & NO MUTATIONS found of 29 genes tested! Thoughts on Accuracy & Possible Causes of PCa.

[john4803]

"We analyzed 29 genes that are associated with colorectal, male breast, melanoma, pancreatic, prostate, and stomach cancers and did not find any mutations."

"Genes analyzed:

APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p14ARF), CDKN2A (p16INK4a), CHEK2, EPCAM, GREM1, MITF, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53"

How trustworthy is the Color test? I have seen that some others have used it on this forum?

So, my PCa is caused by Nongenetic Factors?

My thoughts on Possible Risks?

Spent 1 year in the Army, in 1971, maintaining Nuclear Warheads. Wore Dosimeter to assess radiation risk, while working.

First job, out of the Army, worked 10 years, in an office with inordinate amounts of cigarette & cigar smoke. Am a non smoker (cigarettes' or pot), otherwise.

Very rarely consume alcohol.

BMI 23ish!

Wife, of 51 years, is a Dietitian, & I consume modest amounts of red meat, large amounts of veggies & fruit.

Any thoughts on possible causes of my PCa, would be much appreciated, even though the "Horse is out of the barn"!

[StayingOptimistic]

Give yourself a break. I have heard a doctor a wile ago said” if you gonna get it, you will get it. Nothing to do in order to avoid it”. It’s a very hard question.

[john4803 in reply to StayingOptimistic]

I agree, somewhat, if it is in our genes, however, if not, we should try to educate ourselves in ways that will help us stave off its' progression until the science comes along, for a cure, possibly. And our President says he is going to come up with a cure & I am sure it is a totally nonpolitical-driven statement? 😘 So, we have to, "HOLD ON, I'M A COMIN" (Sam & Dave)! 😅

[StayingOptimistic in reply to john4803]

I am NOT in ANY politics but I remember when president Obama assigned him to take care of it and he went to MSK and met with doctors there. It was in the news and I was so excited that he might be able to do something about it. Nothing happened since then, it’s very complicated problem but I am still hoping he can intervene and do something now especially since he announced a few days ago that he himself had cancer.

[john4803 in reply to StayingOptimistic]

Maybe Artificial Intelligence (AI) can solve it. It is extremely complicated, for sure. My understanding is that Breast Cancer parallels PCa, due to hormonal influence & incredible strides have been made in the metastatic version, maybe being close to a cure?

[tango65]

Most PCs are not associated with 1 germline mutation. There are 5% of the cancer which may be associated with BRCA1, BRCA2, ATM, BRIP1, and MSH6.

The 95% left most probable are caused by mutations in multiple genes

.urotoday.com/journal/everyd....

The color test is a germline test which gives information about your genome. The cancer may have a completely different genome and it is this genome which is useful to determine if the cancer could be controlled with specific treatments.

[john4803 in reply to tango65]

Thanks! Can I say that, without the mutations, in my germline, at least it MAY make it less complicated to treat my PCa?

[tango65 in reply to john4803]

It depends on the mutations of the cancer. My cancer has PTEN lost which facilitates the reproduction of the cancer cells. My genome does not have this mutation.

[john4803 in reply to tango65]

Thanks, but that is not encouraging! 🥵 But I appreciate your candor, because with this disease we need to be totally realistic & knowledgeable. Ignorance is not really bliss, for me, at least!

[tango65 in reply to john4803]

Well, we could phrase it differently. it is a good thing that your germline does not have BRCA, ATM, CDK12, P53, PTEN loss and RB1 etc. mutations since the cancer would have had all those mutations. Since many of those mutations facilitate multiplication of the cancer cells, the cancer would have been very difficult to control. However at the end of the day what really is important are the mutations in the cancer.

[noahware]

What caused your PC? You got older!

Decades ago it was shown that over 50% of men between 70 and 80 years showed histological evidence of malignancy. But the risk of developing clinically significant disease is far lower, and the risk of dying from prostate cancer is lower still.

Disseminated tumor cells can be found in the majority of prostate cancer patients at the time of primary treatment even with no clinical evidence of metastatic disease. The cells can exist in a quiescent state for years or decades, never to wake up. So a man could die in his mid-90s of heart failure while never even knowing he had prostate cancer cells in his body for the past sixty years, because the disease never progressed to the point where it got detected!

Just having PC in an indolent or pre-cancerous form is almost a "normal" part of the aging process of men (in developed economies of the West, at least). But what causes it to become clinically significant in some men would seem to be a combination of genetics, environment, lifestyle and diet, and an unavoidable variety of changes (due to aging and stress) in all the thousands of metabolic and hormonal signaling pathways we have.

So yeah, hard to pin down!

[john4803 in reply to noahware]

Agreed & I will pose you the same question, as I did to tango?

[AlanMeyer in reply to john4803]

Hello john4803

I think cell biology is great fun! It's all about what we really are.

To elaborate a bit more on tango65's and noahware's explanations:

As I understand it, a "germline" test tests ordinary, non-cancerous cells that we grew up with looking for unusual "alleles" (variations in the DNA) of genes where there is evidence that those alleles are associated with a higher incidence of disease - in this case prostate cancer.

Most cancers, including prostate cancer, are diseases of DNA mutation. Those mutations might have started in your ancestors and been passed on to you in the germline, but they might just as easily have happened in you as a result of the conditions of your own life - for example the heavy exposure to smoke that you experienced many years ago. If the smoking were the cause I would think that you would more likely have developed lung cancer before prostate cancer since it is the lungs that are most exposed to the smoke and the incidence of lung cancer among smokers is much higher than among non-smokers whereas the incidence of prostate cancer among smokers is higher than among non-smokers, but not (I think) as much as lung cancer.

Anyway, mutations are not only caused by external factors like smoking, exposure to chemicals, fatty foods, Agent Orange in Vietnam, x-rays, sunlight, etc. They are also part of the normal aging process. When I studied this some years ago it was thought that the mutation rate in our DNA during mitosis (cell division) was 10^-9, meaning that on average around one out of every billion "base pairs" (pairs of nucleotides) in a cell undergoing mitosis produces an error or "mutation" - a new DNA sequence in one of the daughter cells that is not a correct replica the original cell. Since a single cell has on the order of 3 billion base pairs, that means that every cell division produces about 3 mutations most of which are of no consequence but with an estimated 37 trillion cells in a human body, we're talking about big numbers of mutations. Furthermore, some of those mutations will occasionally affect genes that are involved in gene replication and repair. That means that not only do we accumulate mutations over our lifetimes, but we also tend to increase the rate of mutation as we age, causing an even faster increase in genetic damage.

All of this is to say that, when we get old enough, we're more and more and inevitably still more likely to get cancer. In fact, it's thought by some researchers that if we live long enough and don't die of something else, cancer will kill us. That can probably also be said of heart disease, Alzheimers, bone degeneration, and other illnesses.

Of course evolution couldn't care less about our old age. Once we've produced offspring and helped them grow to adults, we've done our evolutionary duty. We're destined for the rubbish heap.

So what I and I think tango65 and noahware are saying is that you might have an identifiable cause of your cancer but there's a high probability that nothing abnormal in the environment is necessary or even likely to have been the cause.

Alan

[john4803 in reply to AlanMeyer]

Great refresher of my one Biology course I took, Alan!

I had a Vasectomy, back in the 80's. I have heard some discussion about that as a possibility but never read anything definitive? Any thoughts?

[AlanMeyer in reply to john4803]

Hi John,

All I can offer on the vasectomy is pure speculation. For what it's worth, my speculation is that the surgery would not likely mutate one's DNA and cause cancer. I searched Google for "can surgery cause cancer" (without quotes). All of the first page of hits changed the search to "can surgery spread cancer". The consensus was that it might spread existing cancer but even that would be rare. I'm still banking on old(er) age as the cause.

Alan

[maley2711 in reply to john4803]

Can't redo the past....why waste a second on it?

[john4803 in reply to maley2711]

"Knowledge is power" & my lack of it got me to GS9 vs. possibly a 7, due to delaying PSA testing. In hindsight, which of course is 20/20, I may have been cured? So, I want to stay ahead of the "Knowledge Curve", when it comes to this disease & a good MO, my own research & this forum are a help!

[maley2711 in reply to john4803]

I'm not sure that scientists/MDs have determined the course of PCa to the extent that they would agree that your cancer was once G 3+4 and progressed to 4+3, and then 4+4 , and then 4+5, and then 5+4? I'm G9...one core of 18, the other one core 3+3...both <10% . PSA at age 64-65 was 4.1.....biopsy not advised per Kaiser guidelines, then at age 70 had another PSA done...7.5 which was stable for at least 2 years thereafter, final diagnosis not completed until just shy of 73...all scans, including PSMA PET, negative. with 8-9 good years after that 4.1 PSA at age 64-65, I can't say I regret not having a treatment that much earlier? Of course, with different scan results, I'd probably have a different opinion!!

I'm having a difficult time pulling the trigger on the ADT + radiation treatment, or surgery with 50% probability of salvage RT + ADT? Docs have not been that helpful in making a decision.... " its a difficult decision" is not of much help!!!!!!!! Providing more info/data re SEs and treatment protocols would be more helpful, but like pulling a tooth IMHO!! sigh!!

[john4803 in reply to maley2711]

Not sure if you are saying I was 7+3 or not, because my bio should show 4+5, initially!

[AlanMeyer in reply to AlanMeyer]

I made some careless errors in my posting above. I've fixed them but won't be surprised if I missed some.

Alan

[noahware in reply to john4803]

Fortunately, Tango answered better than I could! What I do know is, as PC progresses there are many mutations in the cancer that will take place, and some are greatly influenced by the types of treatment. Since I am metastatic, my MO has told me THOSE are probably going to be the mutations to try and analyze (via somatic genomic testing of metastases, not germline testing) to see if they will impact upcoming treatment decisions. It's not an area I know much about, but I'm afraid that's going to change soon enough, as my cancer progresses and we proceed with testing.

[john4803 in reply to noahware]

Yes, I agree! My MO, when I inquired about testing my original Prostate tissue (almost 5 years old), he said the same thing that the cancer has mutated & the old information may not be valid. If we are going to test, we would do it on the cancer that we treating now.

[maley2711 in reply to john4803]

IMHO, forget about this stuff and enjoy the good days hopefully you are currently having !!! Ie, don't overthink this.....as many of us, include myself, are tempted to do...what is going to happen, is going to happen, quite likely no mattter how much "stuff" we read and may think we are understanding, while we may not !!!

[john4803 in reply to maley2711]

It's the engineer (retired) in me to problem solve & this is definitely a Life or Death problem. Of course, we don't want to obsess, too much, because stress suppresses the immune system & that is the last thing we want!

[dico]

The Color test did not find find anything on my husband either. We were really expecting something as his dad died of prostate cancer and his mom died of breast cancer....but nothing hereditary found. He then took the Guardant blood test and several variants/mutations were found, which expanded his treatment options.

[john4803 in reply to dico]

That's not encouraging but I appreciate it!

[KocoPr]

Hi John, i first took the Ambry Genetics. “BRCa1/2 Analysis with CustomNext Cancer” which tested 75 genes now it tests around 92 genes and the found 1 gene RAD50 of uncertain significance. Then i had my tumor tested and found TMPRSS2/ERG Fusion, and MSH6-Loss.50% of advanced PCa have the TMPRSS2/ERG Fusion mutation.

The MSH6-Loss alone is very rare.

[john4803 in reply to KocoPr]

So, did they test your germline, also?

[KocoPr in reply to john4803]

Sorry I didn’t specify, the AMBRY Genetics was germline.

Oh I also later had the color done as part of the “promise” clinical trial, and it didn’t show any mutations as they don’t include the RAD50 mutation i had from Ambry Genetics

[KocoPr in reply to john4803]

Yes that was the Ambry Genetics test Then they tested my tumor (somatic)

“Then i had my tumor tested and found TMPRSS2/ERG Fusion, and MSH6-Loss.50% of advanced PCa have the TMPRSS2/ERG Fusion mutation.”

[rsgdmd]

Nothing on my Color test, but lots of mutations in my genomic test. At least I don't have something that would be passed along to kids.

[john4803 in reply to rsgdmd]

That is what I am hoping, also!

[john4803]

Thanks, for pointing out of all of the various tests, available. Best of Luck!

[DMohr011]

I inherited broken MSH2 and EPCAM genes. The MSH2 genetic is also called Lynch Syndrome and had my first test done at age 50 - Lynch runs in the family. Colon cancer is the main type associated with this gene and with this I was told I had a 80% chance of getting colon cancer in my lifetime, and a 50% chance that my kids inherited these messed up genes.

Telling my 4 kids I have cancer was hard, as most of us have gone thru. Telling them about their genetic statistics and what it means was just, I felt pretty shitty about it. But they needed to know.

From this gene, the PC cancer I have is not a normal PC cancer, doesn't report PSA and they say, is aggressive.

That passing along messed up genetics to the kids and now they all have kids - "thanks Dad" is what they will say, not happily; 'thanks Mom" is what I have been saying.

But the cure is coming for them. dammit, better be....

[john4803 in reply to DMohr011]

Sorry to hear your story but with the CRISPR gene editing tool, who knows what they will come up with in the near or long term future? Of course, in our state of health, we hope it is in former!

[GreenStreet]

Hi John . I have had a load of genetic testing done by RMH in the U.K. Found nothing which is good for my brother and my nephew. However I was asking myself the same question as you have asked yourself. I may post separately with my details. In my case PC detected at age 56. The replies to your post are great and I have read with interest. Take care and good luck.

[john4803 in reply to GreenStreet]

I agree, having been a member of several PCa forums, the knowledge I've seen on this one, is "hands down", the best, so far!

[HarGreg]

Hello John, I was diagnosed in 2020 with PC. My Urologist is located in the Adirondack area. Many health conscious, athletically fit patients. Meeting with him after the biopsy and given the diagnosis! I said to him I don’t understand? I eat extremely well, organic food, 5k walking daily, don’t smoke, occasional glass of red wine, etc. He said to me, If someone tells you that food causes PC, punch them in the face!! Of course he didn’t mean this literally! I tend too believe him!

[john4803 in reply to HarGreg]

My wife, who is a Dietitian, with 50 years of experience, says be careful obtaining nutritional counseling from , Doctors, who typically have minimal training, in this area. Unless cancer is in our genome, poor diet may suppress the immune system & make us more susceptible to viruses & pathogenic bacteria circulating in our bloodstream, in her opinion.

[HarGreg in reply to john4803]

I concur with that eating/diet healthy food and exercising is very important, that is why I practice this regimen! But! What my urologist’s comment was, that all of the above will not exclude a person from having PC! We still do not know what the cause is! I know he has PC patients that are athletes, skiers, hikers, runners, etc. At this time We Just Don’t Know! Hopefully soon we will.

[john4803 in reply to HarGreg]

Greg, yes, if we don't have the mutation, then probably it is caused by exposure to whatever, which we don't necessarily know what that is? But we know the immune system is important in all of this & possibly a compromised one is just another weakness that the cancer can exploit? So, hopefully my sons & grandsons will take it to heart & try to further reduce their risk through healthy choices!

[HarGreg in reply to john4803]

I agree John, and certainly not going to change my routine!

[MateoBeach]

It also means that, if you have kids, you are not passing to them any of those bad genes known to increase heritable risks of breast or prostate cancer. You and they should feel relieved about that.If you had one of these germline mutations your cancer probably would ha e been even more aggressive. It looks like you are still castrate sensitive. Hoping it stays that way as long as possible, John.

[john4803 in reply to MateoBeach]

Thanks, I agree, because I have a son, grandson & nephew, to think about, so far. However, I don't want them to feel a false sense of security & not concern themselves with the possible environmental hazards, too, when I let them know! However, first just trying to make sure of the validity of the test.

Wow, looking at your Bio, you have been through it all & are a "warehouse of knowledge" vs. a "warehouse of worthless knowledge", as I have been accused! I wish you the very best & keep on keepin on!

[JRPnSD]

Same results...no mutations. But that did not stop me from getting GL9 Stage 4 PC. This test is a very small slice of the information of what we do know about PC....and a mere bit of dust of what we don't know.

[john4803 in reply to JRPnSD]

Agreed! From your BIO, I see you have been through a lot, as have most on this forum! Best of luck & try to hang, as they develop the CRISPR technology & "who knows"!

[raoulmaher]

My Oncologist asked me if I had ever had any STI,s as they felt there could be a likely correlation between syphilis and ghonorea in some cases of PC too !

[john4803 in reply to raoulmaher]

None of those nor any risky sex, that I am aware? Interesting, however!

[KocoPr]

Just because the genomic test doesn’t pick up a prostate cancer mutation does not mean you don’t have mutation/s that causes prostate cancer. Remember they only know of a small number of PC genes. I had two uncles, have two brother that have pc and I know it is hereditary from those cases, but yet they only found one uncertain significance gene RAD50.

[john4803 in reply to KocoPr]

Discouraging! Just showing we only know what we know & as I have said, I plan to impart this to my son, nephew & grandson this. And they should be diligent in getting testing & developing healthy lifestyles.

[KocoPr in reply to john4803]

Yes and each year we know more about this cancer and more treatment options. I see in the very near future we will have licked this disease