Perhaps I am misunderstanding the authors’ interpretation. As I read the paper, the authors are saying that for some cancers we should not waste time trying to prevent them because environment doesn't matter. In my view this cannot be the case. 

The authors do not disagree with any of the studies about environmental factors increasing the risk of cancer. They also do not object to age having the known influence on cancer risk. What they say is: that even with a perfectly healthy life and at a young age you can have cancer ("bad luck") and it has a higher chance to appear in areas where the cells divide more often than in other areas (e.g. higher chance for cancer in the colon compared to the brain).

So IMHO they added a new piece of the puzzle to the already existing lore on cancer research without contradicting the existing knowledge. To me it seems like the peer review was working fine in this case (although having Vogelstein as author on the paper would certainly help in and speed up the reviewing process ;-)

Perhaps I am misunderstanding the authors’ interpretation. As I read the paper, the authors are saying that for some cancers we should not waste time trying to prevent them because environment doesn't matter. In my view this cannot be the case. 

I don't think the author's are saying that for certain cancers the environment doesn't matter at all in terms of having an influence on carcinogenics but they are saying that the process of cell division (focused on stem cell division) has a greater impact on cancer formation in certain tissues than environment. There are different ways of looking at it but if you had 2 tissues with equal cell (or stem cell) division rates then any difference in their cancer formation should be related to external factors (not the intrinsic error rate of DNA replicating machinery). The word environment is also a little based on interpretation - most people likely associate it with pollutants. Technically naturally occurring oxygen radicals can considered a part of the environment , cosmic radiation is part of the environment, one could even argue that the intrinsic error rate of DNA replicating machinery is related to "environment" inside of the cell during DNA replication that causes these mutations.

To some degree this also relates to the process of evolution...without the intrinsic mistakes in DNA replication machinery, gaining favourable traits and surviving or gaining unfavourable traits and not surviving, would not exist. Granted, the paper does not consider other factors like epigenetics but I think it provides a good starting point for more detailed investigation into the role of environment and intrinsic cellular factors of tumourigenesis. It's a pretty trivial question with likely a very complicated answer...we'll just have to wait and see what future data shows.

Rather than this incredibly bad paper, with flaws in data collection, representation, and interpretation (  http://ameyer.me/science/2015/01/02/vogel.html ), I suggest you this link:

http://www.cancerresearchuk.org/cancer-info/cancerstats/causes/preventable/

The Holy Grail of molecular biology, the somatic mutation theory, has been discredited. Today, Sonnenschein and Soto's tissue organization field theory (TOFT) provides support for the view that the rising prevalence of disease in the world today is iatrogenic. For example, the entire biosphere has now been polluted with glyphosate, whose toxicity is pleiotropic in the biophysical sense.

Hello

That lung cancer is increased dramatically by smoking. Lifestyle prevention measures have therefore focused on encouraging people to stop smoking .There will always be non-smokers who get lung cancer, and smokers who don't. But overall, there is no doubt that non-smokers as a group develop lung cancer far less frequently than smokers.

According to say Professor Bert Vogelstein, "Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes', but the truth is that most of them simply had good luck."

Summary and interpretation of the study :

The authors argue two-thirds figure comes from the correlation coefficient between stem cell divisions and cancer incidence. While it is the case that the former explains 65% of the variation in cancer incidence between tissues, this does not translate to a percentage of cancer cases. This data is plotted on a log-log axis, and so distance along the plot is not linear. As the cancers with clear environmental factors are more common,I am sorry if I disappoint you , but the basis of Vogelstein is that cancer is caused by mutations, but if something is based on

5% of cases, it already reveals, that this cannot be true. The major problem is that the reality is not looked at: 5-10% by mutation ,15% by infection ANDsome 80% of cases are still (since 85y) sporadic, meaning unknown cause

Second, while this correlation might explain variation between tissues, it does not suggest the source of mutagenesis. Any factor that had similar effects throughout all tissues would vary this plot on the y-axis but have no effect on the correlation. Notably, as the data is plotted on a log axis, even for tissue-specific toxins many fold changes in the incidences of these cancers would still have no effect on the conclusions of this study.

The most difficult issue is how to consistently and accurately calculate the number of lifetime stem cell divisions in a series of diverse tissues. This is extremely difficult and it’s not difficult to imagine such calculations being off by one or more orders of magnitude. Going through their supplemental data frankly I still am not sure how convincingly this was achieved. It’s not a simple matter by any stretch of the imagination.

Additional failures of interpretation in this study suggest little understanding of the data analysis involved. For example, k-means clustering a single variable lends little insight, and with outliers on either end is sure to form two groups with separation near the center of the range. This provides no evidence of there being two "classes" of cancer.

In my opinion, the Tomasetti-Vogelstein paper reveals two kinds of misfortunes. The not-so-sure kind of misfortune is the authors claim that the majority of cancer cases are sheer bad luck (I am sort of tempted to ask here: Are scientists--who are "experimentalists"--supposed to talk about "luck" in a scientific article at all?).

But I am very sure of the other misfortune. That is, the process of scientific and logical evaluation of a manuscript's qualification in a top-notch journal is dubious. The very basis of the paper--the cell division kinetics of stem cells in different tissues--is unacceptable, because no rigorous examinations has been performed to quantitatively evaluate "actual" stem cell division kinetics for multiple tissues in multiple humans at different ages. There may be enough logic why an abridged version of Cameron's Avatar was not published in Science, and there should be no logic why this article should have been there. And, can we ask the authors why they kept mum about big killers like breast and prostate cancers? First, show me "actual" stem cell population dynamics in a large number tissues in a large number of humans at many different ages.

Now, coming to John's question: no, I do not agree with the authors' claim. First and foremost, they did not exclude any acase of cancer incidence where genetic and/or environmental factors--known or unknown--could have played a causal role. That is the second: identify all cancer cases where there not is not an iota of genetic or environmental influence, and exclude these cases from your study. Then, Dr Vogelstein, humanity will salute you for what you say.

IMO, cancer is pluricausal, highly-stereotyped, and initiated by exogenous disruption(s) in biological water dynamics, so-called exogenous interfacial water stress (EIWS). EIWS is cumulative, synergistic, and systemic. EIWS affects all biosemiotic level concomitantly. Most cancer biology and molecular genetics ignores the reality that our internal biological milieu consists primarily of interfacial water.  Wilfred Widdas' work made it clear, to me at least, that our molecular motors are driven in significant part by non-metabolic "fuel" which is trapped and transduced by interfacial water. ELF EM energy from the environment provides the surface energy of water, which exists as polarized oriented multilayers at the interphase of proteins. Both protein function and gene function are "slaved" to biological water dynamics, which is distinctly non-linear.  Neither "bad luck" (somatic mutations) nor "sins of the father" (genetics) explain cancer. On the other hand, EIWS is transgenerational, epigenetic, and supramolecular. EIWS can be mitigated. The initial common pathway to inflammation and disease is purely biophysical. EIWS is the initial common pathway to cancer. EIWS is pleiotropic in the biophysical sense.

%% Given that smoking for example doubles the risk of pancreatic cancer (http://pathology.jhu.edu/pancreas/BasicRisk.php?area=ba), it seems that their analysis of environmental independence may not be solid despite their peer-reviewed publication. What are your thoughts on cancer and environmental factors in cancer risk?

My understanding is that the Science paper is about interpreting the inter-tissue variation of cancer incidence. Apparently, cancer is a function of cell proliferation, regardless of distinct measurements.  Regarding your question, smoking could double pancreatic cancer rate and lung cancer rate both. Thus, the analysis in the Science paper is little to do about the environment effect to cancer incidence. It appears to be a considerable missing gap between the conclusion that cancer is largely random  and the supporting data that cancer is a function of stem cell number and proliferation rate parameters.

Apparently, there do not exist two genetically and somatically identical cells in the human body due to the well-known replication error. Thus, we still have a poor resolution about the molecular genetic basis of tumor even ignoring the stromal cells. Meanwhile, there are clear distinct concepts between cancer incidence, functional and morphological tumor formation, and tumor cells. However, the causes and key risk factors of pathologically and clinically interested cancer conditions, if compared to the inevitable feature of cancer in vertebrates, are largely random per se due to the complexity to be addressed in cancer. Therefore, we might say "Bad genes, bad diseases and bad lucks", see

QJM. 1998 Dec;91(12):861-4.

Bad genes, bad diseases, and bad luck.

Epstein RJ. http://qjmed.oxfordjournals.org/content/qjmed/91/12/861.full.pdf

Organisms are open systems. This involves a continuous exchange of matter and energy with the environment to generate the steady state capable of using these energy sources. About fifteen years ago, consider the set of intestinal microbes as an organ, involved in glucose homeostasis, was almost science fiction, except for the few experts. The environment and foods are heavily industrialized, which means that the air we breathe and the food we eat contain substances that man had never used before. If a substance enters, it is obvious that it will be treated metabolically. What remains uncertain is our knowledge of metabolism, which is, in my opinion, still rough and partial, because we reason still considering the metabolism by sectors, while it is clear that the metabolites, as well as genes, RNAs, proteins, etc. are connected in one single large network of which we know almost nothing and that we are only now beginning to glimpse something. This prevents us to be able to reliably predict the possible biological events triggered by food or otherwise from "non-regulatory substances" that we are forced to metabolize, despite ourselves. An example is the direct interaction of many simple sugars and fatty acids and the genome. We always thought that these substances were to be primarily metabolized in the respective metabolic pathways, but discover their direct interaction with the genome, gave them a functional power that was previously not recognized, i.e., the control of the genome. This is just one example of something we now know (even not well); I imagine that many other biological activities are reasonably still unknown. On this basis, the guard cannot be lowered, because we still have no adequate global knowledge. What has been done by the article in Science, is just an exercise in methodology for quantitative management of biomedicine, but with data still very partial. This methodology deserves of being explored, but it is still too early to draw global conclusions statistically acceptable.

Recently one of our paper entitled "Life and Consciousness - The Vedāntic View" has been published in the Journal Communicative & Integrative Biology. An interesting discussion on this paper can be found at: https://groups.google.com/forum/#!topic/online_sadhu_sanga/Mcv2O-yhqLE

From paper:

"The scientific confirmation of the existence of consciousness in unicellular organisms and plants certainly establishes that the brain is not the source of consciousness. Several decades back, research in medical science has also proven that the brain is not the source of consciousness. In 1970, Robert White and his team successfully transferred the head of a rhesus monkey to the headless body of another monkey. The monkey survived for 8 days.68 Researchers are also attempting to perform the same scenario with human beings.69 It is reported that if a human head has been detached under controlled conditions, it must be reconnected to the circulatory flow of other person's body (which is conscious or living) within one hour.70 Therefore, brain-based analysis for understanding consciousness (neuronal analysis) does not have very bright prospects."

Paper: Life and Consciousness - The Vedāntic View

DOI: http://dx.doi.org/10.1080/19420889.2015.1085138

Journal: Communicative & Integrative Biology

Publication date - 09 Oct 2015

Author: Bhakti Niskama Shanta - http://orcid.org/0000-0002-2039-3249

Check the attachment .

regards