The net result of the interaction of an organism’s genes with its environment.
In 1953, Watson and Crick’s discovery of DNA was a beacon of hope for understanding what causes human disease. Since then science and medicine have invested billions in research and man hours under the premise and promise that understanding our genetic code would lead us to answers and cures for the leading causes of disease and death. To our surprise, the results have not been so straightforward. As we’ve gained more and more information about our genetic programming, we’ve discovered that genetics plays only a small role in the development of many of the leading causes of chronic disease and premature death. Our antiquated belief that we are destined to fall victim to a disease that ended the life of our parents and/or grandparents has given way to the sometimes difficult realization that we have more influence over the future of our health and our lifespan than we could have imagined.
As more and more research has come online, we’ve discovered that many human diseases are largely a result of external factors that are potentially under our control. A study published in 2004 in The Lancet followed over 15,000 people assessing risk factors for heart attack. The authors identified nine non-genetic risk factors that “collectively accounted for 90-94% of cardiovascular disease and had the potential to prevent the majority of premature myocardial infarction1”. These risk factors were composed of external influences that can all be eliminated including “Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity[i]”.
A study appearing in JAMA in 2008 on 4883 people over the age of sixty-five concluded that 90% of DM2 cases are preventable using 5 lifestyle changes. Diabetes-related risk factors include physical activity level, dietary habits, adiposity, alcohol use, and smoking habits[ii].
As our understanding deepens, it is becoming apparent that perhaps these are not diseases at all but in fact what we call phenotypes.
Since 1998, the statistics regarding cancer risk, which were studied separately by the NIH and WHO, have remained surprisingly steady. Despite thousands of new studies every year the figures stood at approximately 80% environmental (a scientific term for external factors) and 20% genetic. This was concurred in 2014 by The American Cancer Society saying, “environmental factors (as opposed to heredity factors) account for an estimated 75%-80% of cancer cases and deaths in the US[iii]. On January 2nd 2015 this assessment came crashing down with the controversial Science article by Cristian Tomasette and Bert Vogelstein titled “Variation in Cancer Risk Among Tissues Can Be Explained by the Number of Stem Cell Division”[iv]. This was an elegant, groundbreaking study that shined a light on the novel idea that some cancers simply occur because of random mutations during stem cell division. Suddenly, part of the 80% environmental aspect had to be redefined. The authors’ unfortunate choice to assign a new value to the environmental influence in the absence of adequate data parameters was incendiary across the media and scientific community. Six of the top eleven most frequently occurring cancer types were not included in this study. Interestingly, each of the excluded cancer types have a huge body of scientific evidence demonstrating that each of them is highly influenced by environmental factors. Among these cancers were prostate, breast, uterine, urinary bladder, kidney and Non Hodgkin’s Lymphoma, collectively, responsible for nearly 20% or 1/5 of cancer deaths in the US in 2014 and their incidence rate an even higher contribution3. The environmental factors that influence their development include infectious agents[v], endogenous[vi] and exogenous hormones, xenobiotic compounds[vii], certain heavy metals[viii], certain pharmaceuticals, specific industrial and organic chemicals[ix], alcohol consumption[x], glycemic control[xi], and aflatoxin[xii].
One reason the scientific community raised such a fuss about the “bad luck” cancer study was that an inordinate amount of funding and resources is already dedicated to the diagnosis and treatment of cancer. The same goes for many other “diseases” including heart disease and diabetes. After all, each one forms a massive economic base that generates billions of dollars annually. Research funding directed towards the understanding and true prevention of these diseases contributes very little to monthly recurring revenues. Instead, it represents an ominous threat to the economic base of the medical industry as well as any industry whose products might be identified as a risk. Despite the hurdles, advances in our understanding of the processes that create these “diseases” has accelerated so fast that it has created a growing chasm where science and medicine no longer overlap but have diverged. The statistics about the environmental influences on “disease” have been well known in the scientific community for at least 15 years. However, they are poorly acknowledged by the medical industry and, as a result, have remained clandestine to the general public. Chemicals aside, imagine if society truly understood how they could prevent diabetes or delay the onset of heart disease simply by adopting a regimen of glycemic control as described in the studies above. What if it was not based on a drug but was based on reducing their consumption of excess sugar? This one change would have massive reverberations through multiple industries. On one side, there would be reduced “need” for medical services that manage the entire sequela of diseases that are known to be caused by poor glycemic control. This would translate into reduced doctor visits, reduced “need” for pharmaceuticals, fewer hospitalizations, fewer surgeries, lower consumption medical supplies, reduced need for assisted living and in home care, reduction of insurance costs etc. On the other side the industrial farming and food complex would also be widely affected. This includes farming equipment, GPS equipment, chemical fertilizers, pesticides, herbicides, fungicides, GMO seeds, all sugar-laden products, packaging, transportation and distribution, fuel consumption etc. As you can see, a significant base of the economy relies on a mutualistic relationship between Big Farma and Big Pharma. The current medical paradigm actually benefits from environmental problems and generally relegates efforts to fix this to the realm of environmental fundamentalism and quackery.
At what point do we embrace our responsibility of removing the known causes of disease? There are already billions of dollars and man-hours wasted on researching and treating diseases that are created by humans literally poisoning themselves. What is the sense? To continue to protect economic interests cloaked inside a societal dietary lexicon that has been hijacked by mass manipulation of naturally occurring, animalistic addictions through marketing, food additives and advertising? We must focus on removing the factors that create these disease phenotypes. Once this illusion has been cleared we can direct our resources towards novel drugs and therapies that will do the most good. Image a healthy, thriving society where disabled life expectancy is a thing of the past. Where companies and organizations like SENS, Calico and Human Longevity Inc. create drugs that don’t depend on illness but address the factors that are not under our control to produce meaningful lasting advances in health and longevity.
[i] Prof Salim Yusuf DPhil,Steven Hawken MSc,Stephanie Ôunpuu PhD,Tony Dans MD,Alvaro Avezum MD,Fernando Lanas MD,Matthew McQueen FRCP,Andrzej Budaj MD,Prem Pais MD,John Varigos BSc,Liu Lisheng MD,on behalf of the INTERHEART Study Investigators Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
The Lancet – 11 September 2004 ( Vol. 364, Issue 9438, Pages 937-952) DOI: 10.1016/S0140-6736(04)17018-9
[ii] Dariush Mozaffarian, MD, DrPH; Aruna Kamineni, MPH; Mercedes Carnethon, PhD; Luc Djoussé, MD, ScD; Kenneth J. Mukamal, MD; David Siscovick, MD, MPH. Lifestyle Risk Factors and new Onset Diabetes Mellitus in Older Adults. Arch Intern Med. 2009;169(8):798-807. doi:10.1001/archinternmed.2009.21.
[iii] [iii] ACS (2014). Cancer Facts & Figures 2014, Atlanta. American Cancer Society, 2014. Available at: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf
[iv] Cristian Tomasetti, Bert Vogelstein. Variation in Cancer Risk Among Tissues Can Be Explained by the Number of Stem Cell Divisions. Science 2 January 2015 Vol. 347 no. 6217 pp. 78-81. DOI:10.1126/science.1260825
[v] Yidya Vedham Ph. D., Mukesh Verma Ph. D. Cancer-Assoicated Infectious Agents and Epigenetic Regulation Cancer Epigenetics Methods in Molecular Biology Nov. 8, 2014 Vol. 1238, pp333-354 Doi: 10.1007/978-1-4939-1804-1_18
[vi] Tim Key; Endogenous Hormones Breast Cancer Collaborative Group Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies. Steroids. Oct. 7, 2014. Doi: 10.1016/j.steroids.2014.09.001
[vii] Hye-Rim Lee; Kyung-A Hwang; Kyung-Chul Choi. The estrogen receptor signaling pathway activated by phthalates is linked with transforming growth factor-β in the progression of LNCaP prostate cancer models. International Journal of Oncology. May 22, 2014. Pp595-602 Doi: 10.3892/ijo.2014.2460
[viii] García-Lestón, J; Roma-Torres, J; Vilares, M; Pinto, R; Prista, J; Teixeira, JP; Mayan, O; Conde, J; Pingarilho, M; Gaspar, JF; Pásaro, E; Méndez, J; Laffon, B. Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair. Environ Int, 2012 vol. 43 pp. 29-36
[ix] Guo, H; Bassig, BA; Lan, Q; Zhu, Y; Zhang, Y; Holford, TR; Leaderer, B; Boyle, P; Qin, Q; Zhu, C; Li, N; Rothman, N; Zheng, T. Polymorphisms in DNA repair genes, hair dye use, and the risk of non-Hodgkin lymphoma. Cancer Causes Control, 2014 vol. 25(10) pp. 1261-70
[x] Qian Zhong, Ganggang Shi, Yanmei Zhang, Lei lu, Daniel Levy, Shuping Zhong. Alteration of BRCA1 Expression Affects Alcohol-induced Transcription of RNA Pol III-Dependent Genes. Gene Vol 556, Issue 1, Feb. 1, 2015 74-79.
[xi] Juhyun Park; Sung Yong Cho; Young Ju Lee; Seung Bae Lee; Hwancheol Son; Hyeon Jeong. Poor Glycemic Control of Diabetes Mellitus Is Associated with Higher Risk of Prostate Cancer Detection in a Biopsy Population. PLOS Sept. 18, 2014. Doi: 10.1371/journal.pone.0104789
[xii] Xi-Dai Long; Dong Zhao; Xiao-Qiang Mo; Chao Wang; Xiao-Ying Huang; Jin-Guang Yao; Yun Ma; Zhong-Hua Wei; Min Liu; Li-Xiao Zeng; Jian-Jun Zhang; Feng Xue; Bo Zhai; Qiang Xia. Genetic Polymorphisms in DNA Repair Genes XRCC4 and XRCC5 and Aflatoxin B1–related Hepatocellular Carcinoma. Epidemiology Sept 2013, Vol. 24 Issue 5 pp. 671-81. Doi: 10.1097/EDE.0b013e31829d2744by
A new study on the “bad luck” of cancer is a wonderful contribution to science but is being severely misinterpreted by both science writers and the media.
This study is the first of its kind to accurately quantify the probability of the development of a cancer cell in any given tissue over a lifetime. It supports other hypotheses stating that increased frequency of cell division, which is also a hallmark of cellular aging, leads to increased risk of cancer. However, it is not representative of a cancer cell’s ultimate destiny. New cancer cells form in our bodies everyday and our immune system destroys them. We’ve known for 20+ years that tissues that are prone to faster cell division and turnover, like colon and skin, have a higher probability of developing cancer cells. This is why inflammation is strongly associated with the development of cancer. Inflammation from immune activity causes rapid damage and therefore places a high demand on the affected tissue for renewal by cell division. Thus, a higher frequency cell division results in a higher statistical probability that mutations will occur, cancer cells will develop and one of them might escape under the immune system’s radar. An example; we know that cigarette smoking leads to a much higher risk of developing lung cancer. There are two parts to this. One is the simple carcinogenicity of some of the chemicals in cigarette smoke. However, a much larger role is played by the fact that the body responds to cigarette smoke by launching an immune response that leads to increased inflammation, increased cellular replacement, impaired cellular death and diminished tissue cleanup,.
Most importantly, the cancer risk study excludes any statistics on breast and prostate cancers. Perhaps these were intentionally excluded from the study as edge cases since their occurrence in the general population is 300% higher than any of the cancers included in the study. Because these tissues are hormone-sensitive, they are highly susceptible to influence by external factors. Hundreds of studies have established their extreme vulnerability to chemicals that mimic estrogen and stimulate rapid growth and cell division. This parallels the theme of this recent study suggesting that faster cell division leads to a high probability of mutations and cancer cell development. Including these two types of cancer in the study’s statistics could increase their external influence factor by as much as 20%.
Although there are some correlations it is important to note that the probabilities in the study do not evenly parallel rates of cancer incidence in the US. For example the study shows, stem cell divisions in colorectal cells as being significantly higher but than in lung but cancer statistics show that the incidence of these cancers is flip flopped.
While this information is invaluable for quantifying cancer cell development, it is missing significant aspects of our basis of cancer knowledge and statistics and by no means establishes final numbers or parameters for cancer risk or its influence by external factors.
 Cristian Tomasetti, Bert Vogelstein. Variation in Cancer Risk Among Tissues can be Exlapined by the Number of Stem Cell Divisions. Science 2 January 2015 Vol. 347 no. 6217 pp. 78-81. DOI: 10.1126/science.1260825
 Steve Horvath. DNA Methylation Age of Human Tissue and Cell Types. Genome Biology 2013 12:R115 doi:10.1186/gb-2013-14-10-r115
 Naotaka Noda, Koichiro Matsumoto, Soturu Fukuyama, Yukari Asia, Hiroko Kitajima, Nanae Seki, Yuko Matsunaga, Keiko Kan-o, Atsushi Moriwaki, Konosuke Morimoto, Hiromasa Inoue and Yoichi Nakanishi. Cigarette Smoke Impairs Phagocytosis of Apoptotic Neutrophils by Alveolar Macrophages Via Inhibition of Histone Deacetylase/Rac/CD9 Pathways. Int. Immunol. (2013) 25 (11) 643-650. doi: 10.1093/intimm/dxt033
 Susan JM Hoonhorst, Wim Timens, Leo Koenderman, Adele T Lo Tam Loi, Jan-Willem J Lammers, H Marike Boezen, Antoon JM van Ossterhout, Dirkje S Postma, Nick HT ten Hacken. Increaded Activation of Blook Neutrophils After Cigarette Smoking in Young Individuals Susceptible to COPD. Respiratory Research 2014 15:121 doi:10.1186/s12931-014-0121-2