Still Smarter to Be Lucky

There was a link to a discussion of this study posted here ... somewhere... already but this New York Times story has a lot more on what the study's writers think it means.

Cancer's Random Assault

I was of two minds about whether to start a new thread for this link or to post it in the Take a Number thread where it fits nicely in the discussion.

The key passage, at least from my point of view, is this discussion of the result that many cancers are mostly attributable to bad luck:

On of the authors said...
For the average cancer patient, I think this is good news,” Dr. Tomasetti said. “Knowing that over all, a lot of it is just bad luck, I think in a sense it’s comforting.”

Among people who do not have cancer, Dr. Tomasetti said he expected there to be two camps.

“There are those who would like to control every single thing happening in their lives, and for those, this may be very scary,” he said. “ ‘There is a big component of cancer I can just do nothing about.’

“For the other part of the population, it’s actually good news. ‘I’m happy. I can of course do all I know that’s important to not increase my risk of cancer, like a good diet, exercise, avoiding smoking, but on the other side, I don’t want to stress out about every single thing or every action I take in my life, or everything I touch or eat.’ ” Dr. Vogelstein said the question of causation had haunted him for decades, since he was an intern and his first patient was a 4-year-old girl with leukemia. Her parents were distraught and wanted to know what had caused the disease. He had no answer, but time and time again heard the same question from patients and their families, particularly parents of children with cancer.

“They think they passed on a bad gene or gave them the wrong foods or exposed them to paint in the garage,” he said. “And it’s just wrong. It gave them a lot of guilt.”

The implication of this line of thought is that, if random genetic changes cause (or at least serve as catalyst for) most (or all) cancer, or produce conditions that then lead to cancer, then stopping those random genetic changes would, in a kind of positive domino effect, lead to stopping the development of cancer itself.

Or is that illogical, in the sense that random genetic changes, being random, can't be subject to any kind of control?

Or maybe it really is possible. It's certainly not my area of expertise, but I do seem to remember reading somewhere once that there can be closed systems, in which certain events occur with random probability, but that certain conditions can then be introduced into those systems by an experimenter that can influence that randomness in a way that the experimenter wishes. That is, the randomness can be controlled.

Could such an approach be made to work for random cell mutations in humans? If so, would this approach prove to be a novel way of approaching cancer control?

Whether the above works or not (any of you engineers or mathematicians care to comment?), clearly the researchers' discovery about cancer as "bad luck," if valid, will have a significant impact on future thinking about cancer.

I think the doctors can make too much of the genetic component. For example, I have a family history of breast cancer, so my Dr insists on yearly mammogram from 30 on. No genetics no early test. Gary's dad didn't get pc until after Gary was diagnosed a bit on the late side with G9. And his dad was taking testosterone which may have contributed.
I'm getting to the point. Fed gov' t no longer recommend psa check until 60 without genetic history. WHY??? Simple blood test all men should get. Earlier the better. If more drs just ordered psa to rule out cancer, we'd have fewer G9 folks. Check out the poll I did about psa at dx. Most were diagnosed with spa less than 5. That is often considered within normal range. Need a a baseline test to look for rise. By age 60, could be too late. Rant over.
Beth for Gary

"Stuff" happens. 

I personally believe it's called "life" 

Sister with BC 35 years ago and still kickin' like it never happened. 

Dad died from complications of a by-pass in '92 at 64 yo. 

I do believe there IS a cause.  And when it's found....it's dead meat.   

 

You're right Jerry, in my opinion. "Luck" is a generic term we use to explain the unknown reason for a given outcome, same as "fate". Nothing happens in life without a "chain of events". An aircraft crash investigation is a perfect example. It takes many links to form the chain that results in an accident, remove one link and the accident doesn't occur. I will submit, Cancer is the same. Luck, fate, ignorance, complacency, fact of life, we all call the same thing something different.

Cheers, Doug

Post Edited (Shaba.Doug) : 1/7/2015 9:23:53 AM (GMT-7)

"Luck" should be substituted with "randomness" as it is a better description of what happens. A random series of cell mutations is more likely to cause cancer than any lifestyle or genetic factors.

Here's a counter-argument:
Bad luck, bad journalism and cancer rates

Here's the abstract of the original Tomasetti & Vogelstein (T&V) article in Science:
Variation in cancer risk among tissues can be explained by the number of stem cell divisions

The Guardian points out that the authors of the study looked at the random variation in risk (which T&V call "luck"), and not the causes of the absolute risk level. (BTW - they did not look at prostate cancer in their analysis).

My take on it is that T&V are presenting a truism that left me yawning. We all know that cancer incidence goes up as we age. That is generally true for almost all types of cancer, except the relatively rare childhood cancers. As we are all aware, PC is almost always a disease of older men, and eventually most men, if they live long enough, will get it. This probably has a lot to do with telomere length. As cells repeatedly divide, they lose length of the DNA end-caps called telomeres. When telomeres get really short, genes start fusing inappropriately, triggering genetic changes that may result in cancers. This effect is in addition to random mutations in DNA whose probability increases with more replications. So age is the#1 risk factor in cancer (*yawn*).

Since we can't stop the passage of time, a more interesting question is what are the controllable risk factors. The loss of telomeres may turn out to be one such controllable risk factor. Changes in diet and lifestyle affect it. There is an enzyme called telomerase that starts to appear in older people. Trials of telomerase-blockers have already begun.

It's as useless to blame luck as to blame anything else we may or may not have done in the past. What is useful is to take responsibility for what we do in the present moment. The huge volume of research that we often discuss in this forum shows us how much we can and will be able to do about it.

- Allen

PDA, your initial posting on this topic here seems misinformative .   While posting this information/link on a prostate cancer support site, you failed to mention that prostate cancer WAS NOT AMONGST THE CANCERS FOUND TO BE MORE “RANDOM” IN NATURE.   PC was not included in the study.   I hope that readers will dig beyond the sensationalistic headlines (and thread Subject-line) before making poor decisions.   In fact, the researchers who published the work seem to feel the same as I do.   In an interview, Tomasetti sought to rectify some of the bad medical journalism which Tall Allen posted about , above, and clarify the limitations of the research.   He said, “Changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others.”   There are over 200 types of cancer (National Cancer Institute LINK ).   Prostate cancer is ONE on that list.   But what we know, and has been posted here many times (thanks, zufus, for the repetitive reminders) is that there are many different variants of prostate cancer.   University of Michigan Cancer Center has catalogued 17 different types.   We recognize the vast differences between the rare, deadly neuroendocrine variant characterized by low-PSA/high Gleason in comparison the several non-lethal varieties of indolent PC.   But all are labeled simply as “prostate cancer” (a disease-naming problem we should discuss in another thread).   Those of us intimately familiar with other types of cancer also recognize that, similarly, there are distinctly different variants of many other different types of cancers, so the 200 identified types of cancer might actually be closer to 2,000 (my back-of-napkin estimate only), or more.   The research reported here looked at a total of 31 types of cancers.   To a limited extent, the reseachers did denote different strains of the same cancer in that they reported Islet Pancreatic Cancer separate, for example, from the Ductal Pancreatic Cancer…these were 2 of the 31 studied.   The Islet Pancreatic Cancer was, in fact, the type of cancer which was the most susceptible to randomness amongst all 31 studied, while the Ductal Pancreatic Cancer was 6X LESS susceptible than the Islet variant to randomness.     PDA, the study’s authors went to great length to emphasize that PROSTATE CANCER WAS NOT INCLUDED in the study.   Nor was breast cancer.    This point was specifically called out by the authors (and by me in another thread, Did you have a family history of prostate cancer? ) because of the high incidence of these cancers (PC & BC), and the resulting high level of interest.   While I don’t suspect the glaring absence of this important fact in your posting was nefarious, PDA, I do think it was neglectful…perhaps sensationalistic.   If it were included in this study, would PC have been labeled as being influenced by lifestyle?   Lots of excellent research already points us to an answer of “yes, probably.”   In another thread, I’ve already listed, 1) the 60-fold global differences in PC incidence, 2) studies of separated twins raised in different lifestyle cultures, 3) the Dr Carroll/UCSF study of low-risk cases where PC-markers went down (improved) with lifestyle modifications.   Not yet mentioned are the studies linking obesity to biologically aggressive PC.   Obesity, in fact, was labeled in a November 2014 ASCO policy statement as having the potential to become “the leading cause of cancer” in the US ( “New” PC InfoLink article ).   Luck certainly is one of the factors in who gets cancer and who doesn’t.   I’ve personally marveled at a uncle of mine who smoked but lived to be 80 years old, but the facts presented in the previous paragraph help point to lifestyle choices as being a likely significant factor specifically for prostate cancer.   As Tall Allen and A Yooper have pointed out, at least take responsibility for WHAT YOU CAN DO in the present moment.   For those who have additional energy, as I pointed out in another thread ( Take a Number ), if you want to also help others in the future , stand up for something beyond yourself and beyond the present…and for THIS group of men, PC prevention—for our sons and grandsons—is a great starting point.   Or, walk away and say, “it just doesn't matter; I already gots what I gots.”

There is a direct causal link between telomere length and cancer. There are biochemical reasons for it -- it causes malignant phenotype alterations - it's not just an association. Telomerase practically disappears post-fetus in most tissues, except in cancerous ones. Inhibition of it looks good in early trials.

BTW, Tomasetti and Vogelstein are researchers at Johns Hopkins.   The excesses of “bad journalism” have caused Johns Hopkins today (January 7) to issue an “addendum” to their initial news release on January 1.     Several points align directly with my earlier comments: ·          “Some have misunderstood [underlining added by me] our research to say that two-thirds of cancer cases are due to bad luck.” ·          “We emphasize that no single factor causes cancer.” ·          “Some risk factors may be outside our control, but others are not.” ·          “In the same way [as a car trip analogy used in the article], we can prevent [underlining added] many cancers.”   The car trip analogy is somewhat informative:   the longer the car trip, the higher the possibility of having an accident; roughly analogous to the longer one lives, the more likely one is to get cancer.   (Age is a significant risk factor.)   But the authors clarify that while “distance” is one factor, “traveling can be made safer by driving well-maintained vehicles, using safety devices, such as seat belts and airbags, and choosing a particular route.”   Read yourself:   Johns Hopkins LINK   ----------   Doug, I’m also glad PDA opened this thread…as I said, I just wish the opening wasn’t so mis-informative.     You, Doug, said earlier in this thread that the focus should be on QOL and treatments.   I would like to see far more focus on prevention.   97% of cancer research dollars are spent on treatments and early detection while only 3% is spent on prevention.   I would like to see a shift to more spent on prevention.   I feel that was overtreated (which I have written about plenty of times here); I don’t want my son overtreated, or my grandsons.   A new 5-armed robot isn’t going to help prevent them from being overtreated; but more knowledge on what environmental factors & lifestyle choices “feed” and “fight” prostate cancer will help.   ----------   Redwing, I agree…good conversation.   But also meaningful to be clear on what the report says and doesn’t say.

Jack you misunderstood me. MY focus is NOW on the QOL and treatment for me. What caused ME to end up with Cancer is history, I'm strictly speaking about me. I wasn't surprised at all with the Dx as I didn't have a healthy lifestyle. I'm not going to fret about it now, too late. I could agree more that more that more money and research be put into finding cause, prevention and cure, for all types of cancers.

Cheers, Doug

Halbert, it's pretty clear when you use the term "stem cell research," you're actually speaking of embryonic stem cell research. Any refutation of your comments would move this discussion into a moral/ethical quagmire, and I don't intend to get sucked in, and I don't think this forum should go there either...but maybe I'm wrong about that.

Since you raise the issue, though, I'll just say that no health condition that I might develop would, in my mind, warrant the destruction of embryonic human life. Period.

Now, adult stem cells are another matter and I trust science will find ways to accomplish good things without the need to exploit human embryos.

Andrew,
I hope your luck continues. A for sure "once" at your age should really be remedied. And for goodness sake make the next one more memorable! Best wishes for a continual decline in your PSA as well.