What Causes Cancer: Bad Luck or Bad Lifestyles? - Comments

[Ygggdrasil]

Ygggdrasil submitted a new PF Insights post

What Causes Cancer: Bad Luck or Bad Lifestyles?

Continue reading the Original PF Insights Post.

 

[Buzz Bloom]

Hi @Ygggdrasil:

A very interesting article. I am wondering if this kind of study might show whether the length of telemeres might play a role. Telemeres shorten with each cell division, and when they are too short, the cell can no longer divide.

Regards,
Buzz

 

[Dr. Courtney]

Nice article, thanks for writing it.

I still have an open mind about the basic question.

The debate highlights the difference between retrospective studies which attempt to test a given hypothesis with available historical data and truly prospective studies which test a given hypothesis by using the hypothesis to make definite testable predictions regarding the outcome of a carefully controlled future study.

Apportioning importance of different causal factors is always a challenge in science when the systems are complex and many factors are in play.

 

[Ygggdrasil]

A very interesting article. I am wondering if this kind of study might show whether the length of telemeres might play a role. Telemeres shorten with each cell division, and when they are too short, the cell can no longer divide.

The studies focus mainly on the mechanisms that create cancer-causing mutations in cells, but they do not address how these cancer-causing mutations lead to disease. A lot of work over the last few decades has gone into figuring out what specific mutations lead to cancer (for a good review see Hanahan and Weinberg, 2000 and Hanahan and Weinberg, 2011), and activation of telomerase is certainly important for carcinogenesis. Nearly all malignant cancer cells are able to extend their telomeres in order to allow unlimited cell division, and this process has been described as an essential hallmark of cancer cells.

 

[Buzz Bloom]

Hi @Ygggdrasil:

Thank you very much for your clear and useful response to my question.

Regards,
Buzz

 

[Choppy]

I just wanted to say that I liked the article. Great post - @Ygggdrasil !

 

[Trinity777]

I liked the article too. I wondered if there would be any correlation between lower "Biological Age" and those with a reduced risk of Cancer. Specifically, can the lifestyle of one with a lower Biological Age change how DNA ages and responds?

As a point of reference for myself, my Biological Age testing hooked up to a machine, came back at 18 years younger than what I am. So what does that do to my DNA specifically? Trinity777

 

[Buzz Bloom]

So what does that do to my DNA specifically?

Hi Trinity:

One idea is that telomeres shorten with age. In some some tissues, this occurs faster than others. If the Biological Age machine measures the length of telomeres of leukocytes, then a correlation of these lengths with age calculated from many samples could be used to make such a assessment.

See
http://longevity.about.com/od/researchandmedicine/p/telomeres.htm .

Regards,
Buzz

 

[Trinity777]

Buzz
Thanks for the link and I get it about the Telomeres length or being too short have an impact both positive for long, not so great for short. I have been thinking about cell regeneration, possibly Telomere regeneration. Is it possible for regeneration to occur instead of death without disrupting the balance?

A hypothesis might be; regeneration instead of total cell/Telomere death. In that scenario the Telomeres would not shorten or when they began the process of shortening a regeneration process would kick in instead. Of course that would mean the "birth" of new Telomeres would not be as abundant, BUT the risk of cancer due to defective and dying Telomeres would then be almost mute? I guess the next step would be to see if we could "encourage" a Telomere to regenerate, finding out what would be the "kick" to initiating that response instead of break down and death. Just thinking out loud.
Trin

 

[Buzz Bloom]

Is it possible for regeneration to occur instead of death without disrupting the balance?

Hi @Trinity777:

I think you are asking if a medical treatment might someday be invented which would either (1) prevent or slow the reduction of telomere length, or (2) would somehow regenerate telomeres by making them longer. I do not personally know of any such research efforts, and I do not have the knowledge to intelligently try to predict future possibilities. I have a thought about a possibility in a different direction. I think it might be possible to lengthen telomeres in ova and sperm is a safe way. This might provide an infant with a longer life expectancy.

Of course that would mean the "birth" of new Telomeres would not be as abundant, BUT the risk of cancer due to defective and dying Telomeres would then be almost mute?

I have no idea what you mean by "birth of new Telomeres".

You have apparently misunderstood the relationship between telomere length and cancer. I do not know if this is always the case, but a normal cell commonly becomes actively cancerous when a cell enzyme which is normally inactive lengthens the cell's telomeres so that the cell can continue to divide abnormally.

Regards,
Buzz

 

[Ygggdrasil]

Thanks for the link and I get it about the Telomeres length or being too short have an impact both positive for long, not so great for short. I have been thinking about cell regeneration, possibly Telomere regeneration. Is it possible for regeneration to occur instead of death without disrupting the balance?

A hypothesis might be; regeneration instead of total cell/Telomere death. In that scenario the Telomeres would not shorten or when they began the process of shortening a regeneration process would kick in instead. Of course that would mean the "birth" of new Telomeres would not be as abundant, BUT the risk of cancer due to defective and dying Telomeres would then be almost mute? I guess the next step would be to see if we could "encourage" a Telomere to regenerate, finding out what would be the "kick" to initiating that response instead of break down and death. Just thinking out loud.

As @Buzz Bloom noted, telomerase is a double-edged sword when it comes from aging. Telomere errosion is one (of many) factors that contributes to aging, so lifespan extension probably requires some means to extend telomeres in senescent cells. At the same time, cancer progression also requires telomere extension, so the worry is that any therapy that extends telomeres would also increase cancer risk.

A large issue, however, is that aging is a multifaceted problem. There are many factors that contribute to aging and if you focus only on one, then the others will kill you instead. Thus, increasing the maximum lifespan of humans requires solving all of the issues simultaneously, a fact made even more difficult because some of the solutions may not be mutually compatible (e.g. the issue of telomere extension potentially promoting cancer). Here's a link to a nice (though fairly technical) review of the biological factors influencing aging. The article points to nine major factors, of which, telomere errosion is only one: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

 

[Trinity777]

As @Buzz Bloom noted, telomerase is a double-edged sword when it comes from aging. Telomere errosion is one (of many) factors that contributes to aging, so lifespan extension probably requires some means to extend telomeres in senescent cells. At the same time, cancer progression also requires telomere extension, so the worry is that any therapy that extends telomeres would also increase cancer risk.

A large issue, however, is that aging is a multifaceted problem. There are many factors that contribute to aging and if you focus only on one, then the others will kill you instead. Thus, increasing the maximum lifespan of humans requires solving all of the issues simultaneously, a fact made even more difficult because some of the solutions may not be mutually compatible (e.g. the issue of telomere extension potentially promoting cancer). Here's a link to a nice (though fairly technical) review of the biological factors influencing aging. The article points to nine major factors, of which, telomere errosion is only one: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

Thank you Yggg. I appreciate the information. I guess my thought was if we could cause a cell or telomere to regenerate rather than decay, we might find an avenue to reduce the incidence of cancer. Of course the overall anti aging aspect is something I hadn't really though about, but imagine when combine with all the other factors it would make sense. Thanks again! Trin

 

[Ygggdrasil]

Thank you Yggg. I appreciate the information. I guess my thought was if we could cause a cell or telomere to regenerate rather than decay, we might find an avenue to reduce the incidence of cancer. Of course the overall anti aging aspect is something I hadn't really though about, but imagine when combine with all the other factors it would make sense. Thanks again! Trin

Unfortunately, longer telomeres and telomere regenteration seem to be associated with an increased risk of cancer. For example, see https://www.ucsf.edu/news/2014/06/114956/longer-telomeres-linked-risk-brain-cancer

 

[Laroxe]

I think this whole discussion may be premature and I see real problems with attributing cause to lifestyle. I base this on a number of issues that may be important in making sense of the arguments. The first would be in the idea that cancer is a discrete disease entity when in reality we are looking at a range of different problems, with different risk factors that result in similar outcomes in the control of cell division. It also seems that cancers really need more changes in the cell in addition to unregulated reproduction, they also need to be able to avoid the systems in place to remove rouge or damaged cells. Childhood cancers as an example, don't fit well into this debate, inherited risk is not well addressed and in fact will also likely be significant the the sensitivity to certain risks, then the role of viruses an increasing area of interest is ignored.
Then there is the evidence around the risk factors which is usually based on very poor methods, in epidemiology its suggested that if the statistics don't indicate a relative risk ratio of 2:1 it should be ignored. With smoking this figure is around 20:1 there can be little doubt about its significance but few of the other associations reach the 2:1 level. Studies on diet for example have major problems in data collection often relying on self reports and give results that are highly variable and inconsistent.
There is however evidence that if a persons lifestyle is identified as a cause of health problems this can have a negative effect on the care they receive, both smokers and the obese are often denied access to certain interventions on the basis of increased risk, which is not supported by evidence.

 

[ConfidentIntelect]

This is close.
Both lead to it but I would assume lifestyles as there are many factors in our environments that can cause cancer, affecting our genes.

 

[Laroxe]

I think the there are strong social values associated with "clean" living that impact on the way in which health promotion is studied and presented to people. Generally there haven't been any major changes (except smoking) in advice since the seven deadly sins (Wrath, Gluttony, Sloth, etc) and in fact little change in the availability in high quality evidence. Many of the ideas we have are in fact clearly wrong, consider the link of obesity and heart disease which is still promoted and yet the incidence of heart disease has been falling while obesity increases. The major risk of death from all causes, and cancer in particular, is age and as average life expectancy increases (and it continues to increase) then the incidence of age related diseases will also increase. The current fall in the incidence of cardiovascular disease and apparently in dementia is unexpected and not well understood but stands as evidence of our poor understanding of what influences these things. Current evidence is usually at the level of "red meat causes cancer" which is both wrong and meaningless. We need specific information that can link an exposure to a specific risk, ideally with a theoretical understanding of how this association works. Virtually everything that happens in our bodies is ultimately under the control of our genes and gene expression is usually under the control something else within the cell or in the cells environment. However generally this has not proven to be a particularly useful level of explanation when it comes to health and disease as it goes beyond what we really understand and can use. Its an area of science, heavily contaminated by politics and medical science is already considered to be among the least reliable subject areas in research, despite its importance.

 

[Ygggdrasil]

I think the there are strong social values associated with "clean" living that impact on the way in which health promotion is studied and presented to people. Generally there haven't been any major changes (except smoking) in advice since the seven deadly sins (Wrath, Gluttony, Sloth, etc) and in fact little change in the availability in high quality evidence.

A few examples of modern cancer prevention methods include sunscreen and sun avoidance (from the realization that UV radiation causes skin cancer) and vaccination (to prevent cancer-causing or cancer-promoting diseases like HPV (main cause of cervical cancer) or hepatitis B (increases risk of liver cancer)).

Many of the ideas we have are in fact clearly wrong, consider the link of obesity and heart disease which is still promoted and yet the incidence of heart disease has been falling while obesity increases.

Smoking is a risk factor for heart disease, so the decrease could be primarily due to decreases in smoking. Most sources cite obesity as a risk factor for cardiovascular disease (example), but you are correct that these are correlations from observational studies that do not show causation.

 

[mfb]

Many of the ideas we have are in fact clearly wrong, consider the link of obesity and heart disease which is still promoted and yet the incidence of heart disease has been falling while obesity increases.

Anticorrelation does not falsify causation. There are so many factors that can lead to those trends, even with a causal connection in the opposite direction.

 

[Laroxe]

A few examples of modern cancer prevention methods include sunscreen and sun avoidance (from the realization that UV radiation causes skin cancer) and vaccination (to prevent cancer-causing or cancer-promoting diseases like HPV (main cause of cervical cancer) or hepatitis B (increases risk of liver cancer)).
Smoking is a risk factor for heart disease, so the decrease could be primarily due to decreases in smoking. Most sources cite obesity as a risk factor for cardiovascular disease (example), but you are correct that these are correlations from observational studies that do not show causation.

Your right of course but in many ways your examples underline my point, the evidence with UV radiation has been supported in a variety of ways and is informed by a theoretical understanding, what I'm saying is that this isn't the case with a great deal of lifestyle advice, if only it was. The role of virus infections in cancer is a growing area of interest but most of the research has been focussed on the development of guidelines and treatments based on what we know about infections rather than at the level of the gene. In fact the introduction of a vaccination for HPV is already associated with significant reductions in cases of associated cancers and represents a real advance in cancer control, in contrast most lifestyle advice appears to have little if any impact on health outcomes. Most of the lifestyle advice we are exposed to is around diet and exercise, the evidence related to diet, changes more frequently than the weather (and I live in the UK) and apparently has no effect on the health advice given.
Apparently work looking at the fall in incidence of cardiovascular disease and Alzhiemer's disease comes from work that controlled for a whole range of known risks and improvements in management, as yet they are unexplained and unexpected, but very interesting.
The idea that negative correlations or anti-correlations don't falsify causation from the other comment, is of course right, but as you suggest there is no evidence of causation to falsify, most of the correlational work does provide ideas about what variables might be worth investigating further but really shouldn't inform health advice. The stuff on diet is more embarrassing than useful and reduces the credibility of all health advice, this is worrying in a world in which Doctors now seem willing to lobby for the legal control of lifestyle choices and the introduction of selective taxation.

 

[Issac Edelman]

We all know you exponentially increase your risk of getting some cancers by smoking or by having an unhealthy lifestyle. Cancer is caused by a combination of factors – hereditary and environmental factors and the bad luck of random genetic mistakes called mutations that occur when healthy cells divide. I came to that researchers found most cancers – including lung, colorectal, bladder and thyroid cancers – possessed large numbers of mutations that were likely to have been caused by extrinsic (external) factors. Only a few cancers had large proportions of intrinsic (internal) mutations.

<Moderator's note: Advertisement removed.>

 

[Buzz Bloom]

researchers found most cancers – including lung, colorectal, bladder and thyroid cancers – possessed large numbers of mutations that were likely to have been caused by extrinsic (external) factors. Only a few cancers had large proportions of intrinsic (internal) mutations.

Hi Issac:

I found the following defining distinction between extrinsic and intrinsic mutations.

http://bio.classes.ucsc.edu/bio105/winter12/NOTES/12%2013%20MUTATION/notes.pdf
The distinction between "spontaneous" and "induced" mutations is based on an operational definition of induced mutations as those which result from intentional exposure of an organism by an investigator to chemicals, radiation or other mutagenic treatment. Spontaneous mutations, then, are those which occur "naturally" in the environment without intervention of an investigator.​

I gather from your post that the reason that there are many more extrinsic mutations than intrinsic is that experimenters create so many extrinsic mutations in their laboratories.

Regards,
Buzz

 

[Buzz Bloom]

This is an addition to the previous post. I apologize for putting this in a separate post, but it has become too late to add an edit to the previous post.
My wife has pointed out to me that the statistics about the number of intrinsic cancer mutations may be underestimated. This is because immune systems destroy some cells with the intrinsic mutations before they might be counted.

Regards,
Buzz

 

[jim mcnamara]

I would research the idea of epigenetic changes to DNA - e.g., DNA methylation and histone binding. These are not mutations per se (defined as an addition, change or deletion of one or more nucleotides). But cellular activity which deactivates DNA sequences or changes other characteristics of the sequence. DNA nucleotide sequences are not changed or altered. Just the ability to use them as they were before the change.

https://en.wikipedia.org/wiki/Epigenetics