Cancer: What’s Luck Got To Do With It?

Cancer: What’s Luck Got To Do With It?

Grandfather smoked like a chimney, ate bacon everyday and lived to be 90. Yet, your best friend, a lifetime vegan who exercised regularly, succumbed to breast cancer in her thirties. We’ve all used these anecdotes to try to make sense of the deadly scourge that is cancer. So do this week’s headlines in the popular press, Biological bad luck blamed in two thirds of cancer cases give us license to bring on the bacon and booze? Not so fast, as the study just published in Science by Johns Hopkins researchers Cristian Tomasetti and Bert Vogelstein was much more nuanced than the headlines suggest.

♦ The premise of the study was the puzzling observation that some tissues give rise to cancers a million times more frequently than others: for example, the lifetime risk of being diagnosed with cancer is 6.9% for lung, 1.08% for thyroid, 0.6% for brain, 0.003% for pelvic bone and 0.00072% for laryngeal cartilage. Even within the digestive tract, cancers of the colon (4.8%) are much more common than stomach (0.86%) despite both tissues being exposed to the same carcinogens and dietary insults. To make sense of this, the researchers turned to cancer stem cell theory: that malignancy is caused by mutations in a small number of stem cells that retain a lifetime ability to divide. They then searched the literature to estimate the number of stem cells in each tissue. What they found was that tissues with higher populations of stem cells were more prone to cancer. This linear correlation (R=0.8; R^2=0.65) was pretty good, extended over 5 orders of magnitude (see graph), and makes sense since we already know that every time DNA replicates there is a finite chance of making errors and that the more mutations in DNA the greater the chance of some of them triggering cancer. In simple terms, a large part (estimated two-thirds; see R^2) of the variation in cancer risk between tissues is due to the difference in their stem cell population. This does not translate into “two-thirds of an individual’s risk of cancer is due to dumb luck”!   

Environmental, lifestyle and genetic risk factors pile on top of the basic risk of random mutations from stem cell divisions. To identify cancer types (red circles) in which the contribution of environmental and inherited factors was especially high relative to the random DNA replication-driven component, researchers used an unbiased clustering algorithm that used the product of the log values of the x- and y-axes in the graph below. What they found was consistent with what we already know about some cancers. Smoking greatly increases risk of lung cancer by ~18-fold for both sexes (23-times in men, 13-times in women), as seen by the higher risk incidence of lung cancer for smokers compared to non-smokers in the chart. People with familial mutation in the APC gene have a 100% rate of colorectal cancer unless the colon is removed. Infection with Hepatitis C increases risk of liver cancer by 10-fold. 

♦ This new analysis explains some puzzling facts: the same APC mutation has a much higher chance of giving rise to colon cancer instead of duodenal cancer because there are 150 times more stem cell divisions in the former compared to the latter. Another example is that basal epidermal cells and pigment cells of the skin (melanocytes) are exposed to the same carcinogen (UV radiation) at the identical dose. Yet, basal cell carcinomas are much more common than melanomas. The authors argue that this is explained by the underlying difference in rates of stem cell division. 

Why should we care about this analysis? Understanding the underlying risks contributing to each cancer type should determine the best public health strategy to tackle it. Early detection should be the main focus for prevention of cancer types largely driven by random errors in DNA replication, whereas vaccines against infectious agents or altered lifestyle will be key to reducing incidence in cancers with high environmental risk.  

REF: http://www.sciencemag.org/content/347/6217/78.abstract

Inset image: http://www.sciencephoto.com/media/254142/view

#ScienceSunday   #cancer  

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101 Responses to Cancer: What’s Luck Got To Do With It?

  1. Dirk Moeller says:


    Thank you for this excellent explanation.


  2. Thank you for this highly digestible synthesis Rajini Rao … this type of post really contributes to demystifying some of these core ‘terrors’ … 

  3. Rajini Rao says:


    Apologies for the fuzzy graph! They should have used larger fonts and less white space in the original figure in the paper.

  4. Sunil Bajpai says:


    Thanks Rajini Rao​. Such a lucid and logical explanation. Always something to learn from you!

  5. Jan Moren says:


    So genetic variation counts as an environmental factor in this particular case? That’s also worth keeping in mind; you can do no more about that (directly, that is) than you can guard against luck.

  6. Jim Donegan says:


    Good article. Will share!


    What about cancers (or at least cell mutation) due to quantum fluctuations? This must happen and we know that some quantum level effects do manifest at the level of living systems (such as with photosynthesis or birds’ sense of direction). It would be interesting if no matter what we do to minimise the known risks associated with cancers there remains a ‘background level’ occurrence that simply never goes away.


    Ref:


    http://m.bbc.co.uk/news/science-environment-21150047

  7. Rajini Rao says:


    Jan Moren inherited germ-line genetic variation counts as a known (“deterministic”) risk factor. It’s a subtle difference from “random” mutations during stem cell division, if that makes sense? You can screen for variants in BRCA or APC genes and opt for preventative surgery. 

  8. Rajini Rao says:


    Jim Donegan random or “stochastic” fluctuations in DNA sequence will only matter if the cell in which it occurs continues to divide. Most cells mature, differentiate and never divide again. A mutation in such a cell might affect how it functions, but the damage will be largely limited to that cell only. If these fluctuations in DNA (i.e., mutations or epigenetic modifications) occur in stem cells, then they have the potential to give rise to a cancerous cell. 


  9. Very clear explanation and the stem cell density was not really brought out clearly in articles I saw earlier this week.

  10. Norman M. says:


    Informative and useful

  11. Rajini Rao says:


    This paper is more about comparing risks between cancers than absolute cancer risks. The so-called non-random factors vary with cancer type. For example, one can compute that in lung cancer, about 75 percent of the overall risk is due to smoking by using the increased cancer risk of 18x  in smokers relative to non-smokers, multiplying it by the fraction of population that smokes (18 percent adults in the US), and dividing by the total lung cancer risk. 


    Here is a better explanation of what I just wrote by a biostatistician 🙂


    http://www.theguardian.com/science/grrlscientist/2015/jan/02/bad-luck-bad-journalism-and-cancer-rates


  12. Thank you Rajini Rao for the explanation. Learned stuff that is new to me today. (feels brain cells growing)

  13. prem mundada says:


    Happy new year Rajini Rao​ keeping in mind


  14. «Biological bad luck blamed in two thirds of cancer _cases»_


    In fac, the headers I read were talking about cancer types, not cases. That would be the reality, innit?

  15. Rajini Rao says:


    Yes, exactly right Víktor Bautista i Roca .

  16. Azure Rain says:


    I am so glad I started following you. You have really made rational sense with clarity and nuance of a scientific paper that the news media predictably screwed up in a blunt and unfortunately dangerous fashion. I hope to read a great deal more from you in the future.

  17. Rajini Rao says:


    Azure Rain thanks 🙂


  18. Thanks for clearing the air Rajini Rao 


  19. Sweet Slid, but popular science reporting sucks. Don’t even get me started on the “telepathy” stories…

  20. Adit Morey says:


    It was interesting to know that random replication of genes due to stem cells can also contribute to causing cancers, along with environment and lifestyle. This fact should be considered when stem cell therapy is recommended for some autoimmune diseases like muscular dystrophy. 


    Wish you a very nice, happy and positive 2015 too.

  21. Rajini Rao says:


    Adit Morey thank you for that thoughtful comment on the cancer risk associated with stem cell therapy. This is indeed considered a major risk factor in transplanting stem cells. For anyone interested, I’ve left an open access link below. There is anecdotal evidence of a young person who received neural stem cells and later developed brain cancer (described in the linked article).


    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070641/


  22. That was really interesting and clearly explained, thanks! 🙂

  23. Rajini Rao says:


    Nikos Carcosa journalists have to walk a fine line between headlines that pull in readers and reasonable scientific accuracy. It’s a tough job, and they seem to fall more on the sensationalistic side than on accuracy. Perhaps, the study authors ought to submit a press release that they write themselves, when their paper is accepted. Some journals ask for a lay summary, which also undergoes peer review to protect against BS 🙂


  24. Unhappy headings to make stumble some journalists hunting for scoops. The message of the article is addressed more to health authorities and politicians than biologists in order to extend the early diagnosis to most people.

  25. Chad Haney says:


    Great post Rajini Rao. I’ll have to look at the pub to see if they discuss the influence of stroma. For example, prostate cancer tends to preferentially metastasize in bone. There’s a stroma specific response in the bone but I can’t remember the role that stem cells play.

  26. Rajini Rao says:


    Thanks, Chad Haney . The paper does not discuss metastasis or anything relating to matrix/stroma effects. Actually, they omit prostate and breast cancer from their analysis because they couldn’t get a consensus on the stem cell population in these tissues from the literature. 

  27. Chad Haney says:


    That’s not surprising and was a good idea to omit breast and prostate cancers.


  28. In my dad’s words, wonderful!


    Rajini Rao , most critical part which is getting lost in other places and on the news circle is what you posted-


    I quote


    “This paper is more about comparing risks between cancers than absolute cancer risks. The so-called non-random factors vary with cancer type. For example, one can compute that in lung cancer, about 75 percent of the overall risk is due to smoking by using the increased cancer risk of 18x  in smokers relative to non-smokers, multiplying it by the fraction of population that smokes (18 percent adults in the US), and dividing by the total lung cancer risk. 


    Here is a better explanation of what I just wrote by a biostatistician 🙂


    http://www.theguardian.com/science/grrlscientist/2015/jan/02/bad-luck-bad-journalism-and-cancer-rates

  29. Rajini Rao says:


    Thanks for bringing this story to my attention, mandar khadilkar . Hope it made sense. 


  30. It made all the sense. See the comments you always get! 😄👍👏

  31. S Ikhwan says:


    Rajini..a wonderful explanation a well written thesis..this is what we call Faith

  32. Mani A. says:


    Have we really moved from a statistical model?

  33. Rajini Rao says:


    Mani A. I’m not clear what you mean by your question?

  34. John Enfield says:


    Cancer doesn’t make any sense because it isn’t what we usually think it is.  We’re going about the ‘fight’ against cancer all wrong.

  35. Chad Haney says:


    John Enfield that’s a pretty general statement. Can you enlighten us on how we should be doing cancer research right?

  36. Mani A. says:


    Rajini Rao


    I mean the model still remains statistical in nature. We have more rules in them though.

  37. Rajini Rao says:


    Mani A. I can’t agree with that. The field of cancer research is extensive and there are many experimental and theoretical models, vastly more of the former, actually. Any good theoretical model is expected to improve over time as more, and better quality experimental data become available in the literature.

  38. Chad Haney says:


    I’m actually in the process of starting a collaboration with a researcher that models how the immune system is involved with cancer. I can either provide data to feed into the model or plan experiments to test the predictions of her model.

  39. Rajini Rao says:


    Chad Haney you bring up a good point. The best theoretical models explain empirical and experimental observations, that in turn, refine the theory.  


  40. I was interested due to the initial comment. and it said nothing to really deal with it. George Burns, My grandfather, a long list of people I can Identify, don’t fit the common pattern of risk. I was hoping it was about that. not general population cancer.

  41. Ivan Carmona says:


    Love your explanation

  42. Rajini Rao says:


    Jason Brenton in that case, this quote from Dr. Vogelstein is for you:


    “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,” adds Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.”


    See: http://goo.gl/ZArA3J

  43. Jim Carver says:


    Rajini Rao So how does that explain how ‘good luck’ runs across parallel to genetic lines?


  44. Is lucky to be alive 🙂

  45. Mani A. says:


    Rajini Rao


    So you are saying that there are causal models that avoid frequentism (at least) and perform well enough?


    But the terms ‘random mutation errors’ and ‘risk’ remain part of the discourse. AFAIK there are no comprehensive rough set models in the area .


    ps. cancer research is not my area.

  46. Rajini Rao says:


    Jim Carver a generic response to your general question would be that cancer is the outcome of many factors, which include environmental, genetic, lifestyle and stochastic events. I can’t be more specific than that, I’m afraid. 

  47. Rajini Rao says:


    Mani A. still not clear what exactly your point is, so let’s just stick to the paper under discussion here. Thanks. 

  48. Rajini Rao says:


    Jose M. G. Guerreiro indeed, yes 🙂

  49. Jim Gorycki says:


    I read this article the other day, waiting for Rajini Rao to respond.  Thanks.  Does this mean high school biology books have to be re-written to emphasize more on chaos theory? 

  50. Rajini Rao says:


    Jim Gorycki what an interesting idea. Introducing chaos theory in high school would be a good way to emphasize early on the idea behind stochastic and random behavior in complex systems. I often have trouble explaining such behavior at a single molecule level as well, when behavior is a probability function and occurs randomly, such as the movement of kinesin motor along a tubule or the opening of an ion channel. 

  51. Adit Morey says:


    Rajini Rao Thanks for the link. I have been suspicious and wary of stem cell therapy due to a personal reason too, but if we look at how the process is carried out , one question arises – a cell is a quite complex biological system. How certain can one be, that the cells harvested from bone marrow and changed according to the purpose, will not work properly or cause problems like cancers?


  52. This may be too new age or spiritual or unscientific for some but I think part of cancer is possibly recuring negative mental loops.

  53. Rajini Rao says:


    Chris Alexander well yes, there’s no scientific data (that I know) on whether mental status predisposes one to cancer, although the converse is known to be true: one in three cancer patients is also suffering from anxiety, depression or other mental health challenges. 


  54. Aren’t biological events occur by chance (or luck) anyway? Be it one’s birth (chance of gametes fusion), inheriting genes from both but expressing that from only one parent (which one?), or getting one’s DNA mutation that may lead to cancer just because it replicates, aren’t all primarily product of probability or Luck!

  55. Rajini Rao says:


    UmEsH YaDaV well, think about this. If everything in biology was left to random chance, would life as we know it exist? 🙂

  56. Jim Carver says:


    Rajini Rao Life is thought to originate by chance unless a person believes in supreme beings. The atoms are common in the universe for life and they have a preferential way of lining up. So you could look at it both ways: there are chance interactions, which eventually form or can form into those molecules necessary for life, but if the molecules are there, then what is the chance of those getting together in a functional unit?


    The goop is easy to see, but the cell wall? That’s a big question. Stromatolites might be the answer…somehow the compounds got organized within the rock. Maybe the teaming soup figures this out finally on its own…of course that takes a few billion years here. Not sure about anywhere else though. And there could be other chemical pathways we don’t know about…like the organisms near ‘black smokers’ at the mid-ocean ridges. We would have never imagined that process without seeing it. But they did evolve, maybe separately and if you accept that, then it’s possible that life always finds a way under certain conditions.

  57. Rajini Rao says:


    I don’t think that’s what the commentator meant, Jim Carver. By his analogy, left to chance, he would never have been born. The chance that 23 pairs of chromosomes segregate in perfect synchrony, not once, but millions of times to make a person would be infinitesimal. You know quite well that I don’t subscribe to creationism. So let’s not argue for argument’s sake. I’m not discussing abiogenesis in this post. 

  58. Jim Carver says:


    Rajini Rao Oh, sorry, I thought you might like the geology part.


     Since that was really all it was, and I’ve never heard the word abiogenesis.

  59. Rajini Rao says:


    Geology is very cool! Abiogenesis is the way inorganic compounds come together to make basic biochemicals, like nucleic acids and sugars. As you described, by self organization near hot vents. 

  60. Jim Carver says:


    Hmm, new one on me…learn something everyday I guess…see you later.:)

  61. Mary Thomson says:


    well as luck would have it,insurance won’t cover it either…

  62. Kam-Yung Soh says:


    Rajini Rao You and Hedwig Pöllöläinen should get together to write some excellent articles…};-)


    She and Bob O’Hara have also written a piece debunking the “2/3 of cancers is dumb luck” headline [ http://www.theguardian.com/science/grrlscientist/2015/jan/02/bad-luck-bad-journalism-and-cancer-rates ]

  63. Rajini Rao says:


    Thanks, Mark Bruce . A lot of folk have been confused by the mixed message from the news headlines. 

  64. Stuti S A I says:


    Thank you for the post, Rajini Rao It’s very interesting!


  65. Rajini Rao​, I think life does involve random chance, but environment, prehistoric or present, plays biasing (important) role in directing it through evolution. Come to think of it, even cancer could be seen as evolution contrived phenomenon. If not random events, can we call them predetermined, premeditated, but then it falls into creationism! God send me back to be (re-)born! 🙂


  66. Read this interesting article a while ago, may interest the readers of this post.


    http://www.scientificamerican.com/article/did-cancer-evolve-to-protect-us/

  67. Adit Morey says:


    Rajini Rao​​ I meant to say that how certain can one be that stem cells will work properly and not cause problems. I just realised the typo error today morning as it was late when I was typing yesterday and I was tired too.


    I’m very sorry about that. :(


  68. Yes, thanks for clearing this up Rajini Rao This article has created such a stir in the online world & I have read many reviews. 


  69. “Understanding the underlying risks contributing to each cancer type should determine the best public health strategy to tackle it. Early detection should be the main focus for prevention of cancer types largely driven by random errors in DNA replication” – this is what you said in your post above. Rajini Rao  If so there was a global survey with over 100,000 subjects for the most common cancers by McKinsey (the management consulting firm) almost 15 years ago established clear links between Meat consumption, particularly Red meat and Collan cancer – why that is been ommitted – with you and the new surgeon’s general being Vegetarians (I assume you’re a Veg) – why there is a hesitation to publisize this simple fact. Smoking=Lung cancer (high chances) Eating Red meat= Colon cancer (high chances).


  70. All great info, however: Do we really think that the drug industry can afford to cure cancer? My father and brother died from cancer and my sister survived a double mastectomy. They all had the “bra ca”gene. My mother just had her thyroid removed due to cancer which spread to lymph nodes. She is 74. Now studies show that the major cause of thyroid cancer if I am correct, is infection/virus in the mouth. My question is that is it just me or do we not have good Dental insurance because the drug industry could not afford for us to have healthy teeth because we would have less heart disease, cancers etc…because of this? It is the crap in foods, in the air and the water that is doing us in as well. Doctors are taught to treat the condition not to cure it. One can only wonder. Conspiracy theory? Maybe. We should open our eyes and look for things like b17 that is known to cure some cancers because the portion of the capsule that contains cyanide is only activated when it comes into contact with a rogue cancerous tumor and does not kill healthy blood cells like radiation and chemo therapy does. We are always told that modern medicine is the right way to go. Sometimes maybe, but many times, the experimental poison is used on people who have exhausted all western medicines possible and so the rest of your life is spent in horrible pain. My father was taking an experimental drug for the last year of his life but he lasted longer than most on this drug because my mom was feeding him herbal teas that kept his liver in good shape. As soon as he told doctors what he was doing, they made him stop all other treatment and he died about a month later. 


  71. Rajini Rao I do appreciate your information that you have posted. I have just been through so much cancer in family and friends that I am a little skeptical as to the true reasons behind the inability to cure cancer. Or at least the lack of empowerment from doctors to allow a patient to find other means to treating disease if it in fact works for them.


     


  72. Leonardo Caputo I agree with your theory. Thanks for the insight.


  73. Mary Thomson Exactly, most of us could not afford the option because it is not available through Insurance. It does make sense for population control. Survival of the fittest or of the one who does their research and saves them self. 

  74. Rajini Rao says:


    Adit Morey any form of therapy carries potential benefits and risks that must be weighed carefully, and stem cell therapy is no exception. Stem cell therapy is still in its early days and will no doubt be made safer and more effective in the future. Currently, it is used to treat patients under life threatening conditions or severe disabilities. The review that I linked to does a good job of weighing pros and cons. 

  75. Rajini Rao says:


    Krishnamurthi CG research on dietary links to cancer, including red meat, have been extensively published and I’m not aware of any attempt to withhold them from the public. There was one study in the news, published in PNAS, very recently and broadly discussed on G+ and other social media. The food pyramid guide to eating from the USDA already emphasizes fruits and vegetables. 

  76. Rajini Rao says:


    Sandra Stevens I am sorry to hear of your family’s predisposition to cancer. At least  you know about the BRCA mutations now, and they can be screened for early detection. It is easy for frustrated families to seize upon conspiracy theories, however, there is no logical reason or evidence that stands up to scrutiny that physicians, researchers and pharma are preventing progress in cancer treatment. The evidence is quite the opposite: there have been huge gains made in detection, prevention, treatment and survival outcomes for many forms of cancer, although some cancer types are still very difficult to treat. As for alternative therapies, there is a well known saying that any “alternative medicine” that is proved to work becomes 


    “medicine”. 

  77. Chad Haney says:


    Sandra Stevens, I’m a cancer researcher and I drive a VW. If big pharma was really paying researchers off so that they can continue to make money, then they must have the wrong address for me. I’m sorry to hear that your family has been affected by cancer. It is rare for me to find people who do not at least know someone who was affected by cancer. It helps keep me motivated when I’m doing something tedious in my research. Keep in mind that not all cancers are the same, as evidenced by Rajini Rao’s post. Even within a single breast of a single patient, there can be histologically different tumors, i.e., they look different under the microscope using different stains.


    Cancer is complex. For ethical reasons, we cannot test disease models and drugs in humans. I can’t tell you the number of times that a type of cancer has been cured in mice only to fail in humans. Many of us are working hard to improve the translation from mice to humans but the lack of funding from the government is currently the biggest set back.

  78. Chad Haney says:


    Timothy Mckiness I’m not following your comment. It is common to check basements for radon and vent them appropriately. I don’t know about putting “something” in the Great Lakes.


    http://www.cancer.gov/cancertopics/factsheet/Risk/radon

  79. Rajini Rao says:


    Timothy Mckiness I agree with Chad. Venting basements for radon is standard practice in the US. There is no evidence linking GMO with cancer. Please, no conspiracy theories on this thread. 

  80. Chad Haney says:


    Sorry Timothy Mckiness, I’m a scientist. I don’t believe in conspiracy theories. It’s the easy way out. For ever fact a person provides, a conspiracy theorist can simply say that the data can’t be trusted because of the conspiracy. It’s very convenient. Do you have any proof, from peer-reviewed research?

  81. Rajini Rao says:


    Chad Haney I had to block Timothy. Otherwise this thread will devolve into anti-govt/anti pharma rant that has nothing to do with the topic of the post. Thanks for stepping in. 

  82. Chad Haney says:


    Rajini Rao, as you know, I’ve been involved with cancer research for over a decade. It’s rather offensive when someone implies that all of the work that my colleagues and I have done, is all in vain because the government and/or big pharma want people to stay sick. I’m not saying that I’ll cure cancer or even make a major contribution. Nevertheless, I want my work to count for something, otherwise I’d be a fool.


    I know you feel the same about your work. You don’t put in countless hours of research knowing that it will never contribute to the cure of some disease, not because of the quality of your work but due to a conspiracy.

  83. Jim Carver says:


    I think it’s unfortunate that the commented entries were deleted. I’m sure I wouldn’t agree with them, but without the luxury of being able to read them…

  84. Rajini Rao says:


    Jim Carver no comments were deleted by me. I can’t prevent others from deleting their comments. That said, we have better ways to waste our time 🙂


  85. I appreciate the information provided in this post & don’t want to take up more of Rajini Rao time. However, I read a few articles like this http://www.pnas.org/content/99/20/12889.short  on risks associated with stem cell therapy.  My question for anyone is: Is there any research happening in the area of screening stem cells for genetic malformations? (Prior to using them for treatment)

  86. Rajini Rao says:


    Cheryl Ann MacDonald I am attaching a link to an open access paper that summarizes ways in which the risk of tumor formation can be reduced in stem cell therapy. First, not all stem cell (SC) types carry the same risks, and the more differentiated they are during implantation, the less likely to form tumors. MSC (mesenchymal/stromal type) are a lot safer than ESC (embryonic) and iPSC (induced pluripotent).  Tumor initiating cells are similar, but not identical, to stem cells so a better understanding of how they differ could help design strategies to eliminate such cells from a stem cell population. Other ways include destroying any remaining stem cells after they have differentiated into the desired cells (either before implanting or in the patient) using “suicide genes” or targeted drugs.


    Some approaches are diagrammed here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733374/figure/fig02/
    *Paper*: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733374/


  87. Mandar Khadikar’s story and Rajini Rao’s professional explanation of ‘ cancer and luck, ‘ have made so many people, to understand the basics of the topics. I request Kiran Rao, to keep sharing her vast knowledge in the subject, with the lay and non medical people, and make them aware of ‘ do’s ‘, and ‘don’t s ‘, to avoid cancer. ………….Thanks.

  88. maria nasir says:


    Amazing and insightful as always Rajini Rao ! Thank you so much for sharing this. My husband has been smoking for years now, and has some hereditary issues too. It’s a must read for him !


  89. my two cents about Berts paper, and the firestorm of negative reactions…


    Cancer is caused by somatic mutations in genes that control cell growth, death, or differentiation. the probability of a somatic mutation occurring during any one particular cell division can be increased or decreased by environmental factors (radiation, smoking, etc) or by inherited mutations in genes that are supposed to copy DNA properly or fix DNA mistakes before they are passed down (HNPCC genes, BRCA1, BRCA2). However, the somatic mutation rate can not be driven down to zero. Even if you inherited a pristine genome from your parents, and even if you avoid all known mutagens, the chance of a DNA mistake happening during cell division is still non-zero. Basically the DNA polymerase that copies the DNA is good, but it is not perfect. So you can minimize your risk, but you can not eliminate it. Since mutations can only happen during cell division, the number of cell divisions a person experiences during their lifetime increases cancer risk proportionally. you live twice as long, you are somewhat more likely to develop cancer. also, within a person, different organs have different numbers of stem cells and different lifetime renewal rates. tissues that have more dividing stem cells are more likely to produce cancer (compare the incidence of colon cancer with that of heart cancer). Now, this issue has certain psychological, emotional, and for some, religious implications. Paradoxically, the true random nature of cancer causing somatic mutations comforts those who have been afflicted by cancer but simultaneously scares the daylights out of those who have not been affected by cancer. the former are glad to learn it was not their “fault”, while the latter are terrified that “appeasing the gods” is useless, and they may be next.

  90. Rajini Rao says:


    Phillip Buckhaults thanks for the excellent analysis. I would just clarify that mutations can also occur by exposure to chemical mutagens or radiation (environmental factors), outside of DNA replication during cell division. The damaged DNA is repaired, but the repair process can introduce mutations. 


  91. Indeed.  mutations could be induced to happen unrelated to cell division.  but i suppose that the errors that are caused by the imperfect DNA polymerase are all that are left after removing all environmental influences, which is precisely why cancer incidence across different organs correlates so well with the number of stem cell replication events in that organ.  cancer is intimately coupled to DNA replication.  it may actually be a by-product of species capacity to evolve.  

  92. Rajini Rao says:


    Interesting, thanks for the link Akeel M .

  93. Mark alwell says:


    Doc grover suggest drink green tea, pH of 9.0 base the acidic glucose starving cancer (lactic acid)

  94. Mark alwell says:


    I drink diet coke, in mexico is is called coca cola light, found the 10,000 times the sweetness on which sweetener

  95. Rajini Rao says:


    Hey, Mark alwell perhaps you meant to comment on my next post which is on artificial sweeteners and diet sodas? 🙂


    It’s here: https://plus.google.com/u/0/+RajiniRao/posts/da8yW9Zsdiw

  96. Chad Haney says:


    It’s an artificial comment but sweet nonetheless.

  97. Rajini Rao says:


    Yeah, a waist is a terrible thing to mind, so the diet comment stays 🙂

  98. Jan Moren says:


    Rajini Rao How long have you waited for a chance to use that line? 🙂


  99. Each of us has a decisive influence on own lifestyle. Thanks to this we can avoid many illnesses, including cancer. If we do not smoke, take drugs and abuse of alcohol, and, above all, cram, we live healthier. What we have genes is independent from us. If we are able to do so we may also change the environment, which is often very harmful to health. The choice we have, however is small.


    A lot depends on our personality. What we know about the risks, we have to have attitude, then how can we deal with addictions, and we have the motivation and the desire to combat harmful external factors and internal for our health. The key is our psyche.

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