A very intriguing (and worrisome) paper published by Science (Tomasetti C. and Vogelstein B., Variation in cancer risk among tissues can be explained by the number of stem cell divisions, Science 2015, 347 no. 6217 pp. 78-81) casts doubt on the relevance of environmental factors in carcinogenesis.
In addition, it posits that a wide array of cancer types arise from an increased rate of random mutations occurring in tissues with high replication rates. The Authors conclude that, out of 31 cancer types considered, 22 were primarily associated with random genetic mutations (they called these “R-tumors” – the R standing for “random”), and nine were associated with environmental factors on top of these random mutations (deterministic tumors, or “D-tumors”). About 70% of these tumors were claimed to be predominantly determined by random mutations (“bad luck”) and not environmental factors.
Unfortunately, comments by the specialized and lay media have emphasized the “bad luck” aspect, drawing the very simplistic and misguided conclusion that cancer onset is no longer a matter linked to environmental and lifestyle.Instead, it (almost) would entirely rely on stochastic fluctuations, which was translated into “bad luck”.
I reckon that, if it not for its seriousness for cancer patients,we should be bemused by this episode in the long standing controversy about cancer theories. First of all, environmental pollution and lifestyle are relevant issues in disease pathogenesis at large (not only in carcinogenesis). They should not be overlooked or belittle. For the media to claim that lifestyle isn’t important, based on misinterpretations of what the research shows, is highly irresponsible. These arguments, especially when they are widely amplified by media articles, are likely to open the door to an abdication of responsibility when it comes to environmental health by industry and international, national and local public health institutions. Why spend funds on preventing environmental threats or in performing safety tests when pollution doesn’t matter? Statements such as those of Tomasetti and Vogelstein and their uninformed media followers only generate discouragement and confusion in our globalized world.
Secondly, the claim that ‘random mutations’ are associated with increased frequency of cancer, clearly supports the somatic mutation theory of cancer (SMT), according to which cancer arises as a consequence of point mutations affecting proto-oncogenes or anti-oncogenes. Yet, the report does not provide evidence backing up such claim. Indeed, if cancer rates are statistically associated with ‘random mutations’, the mechanistic link between those mutations and cellular biochemical pathways becomes unavoidably lost. High frequency of those genomic changes has been found in some cancers. However, this correlation only suggests that tissues with high replicating rate display higher chance to develop tumors. Notwithstanding, genetic alterations found in cancerous tissues are not cancer-specific, given that they are frequently observed in normal tissues (Washington C, Dalbegue F, Abreo F, et al. Loss of heterozygosity in fibrocystic change of the breast: genetic relationships between benign proliferative lesions and associated carcinomas. Am J Pathol 2000;157:323-9), and mostly in tissues affected by reactive or inflammatory processes (Yamanishi Y, Boyle DL, Rosengren S, et al. Regional analysis of p53 mutations in rheumatoid arthritis synovium. PNAS USA 2002;99:10025-30). On the other hand, high proliferating tissues undergo a wide range of architectural changes and structural rearrangements, and are thereby more prone to experience topological reorganization as well as modification in their biophysical properties. Those alterations may likely be transferred through mechanotrasduction to the cell, where they affect cytoskeleton and nucleoskeleton architecture, as well as many cellular functions. Evidence favoring this view is represented by cells carrying the same gene mutations displaying a very different cancer rate according to the tissues in which those cells are located. For instance, in animal bearing APC-gene mutation, cancers occur mostly in the large intestine rather than in the small intestine, despite having comparable proliferation rates. In other words, the presence of a well-known mutation does not explain cancer onset. How can such paradoxical data be explained?
Undoubtedly, it has become unavoidable to re-evaluate the data collected during a century of cancer research dominated by the premises of the failed SMT and to consider alternative theoretical approaches aimed at explaining carcinogenesis. Such alternative theoretical framework is provided by the Tissue Organization Field Theory (TOFT) originally proposed fifteen years ago by C. Sonnenschein and A. Soto.
Finally, I deem that the consequences of the “bad luck” conclusions drawn by Tomasetti and Vogelstein will end up being worrisome for SMT advocates, an outcome they may not have aimed at. After all, perhaps it is not a matter of ‘bad luck’, but a matter of ‘bad theories’.
In "The New Alchemists: The Risks of Genetic Modification" the author presents GMOs, without any ideological bias, as viewed by biologists, physicists and other scientists, not just as understood by the small group of biologists who are involved in studies of (agricultural) transgenesis. He discusses the issue of plant biotechnology in the light of advances in complexity theory and non linear science; This more rigorous point of view has never previously been attempted. The text is sustained by more than 900 up-to-date (through 2011) references.
Fifteen years after the first genetically modified seeds and food, only four genetically modified plants have achieved significant market positions: corn, cotton, rapeseed and soybeans. Most of the other new constructs have caused unsolved problems or are only at the project stage, demonstrating the complexity of the task facing biotech companies.
La pesante eredità dell’ “eredità mendeliana”.
È ampiamente noto che Gregorio Mendel è considerato il fondatore della moderna genetica la quale è attualmente una branca delle Scienze Biologiche che si prefigge di conoscere e isolare i determinanti ereditari che stanno alla base dei più svariati fenotipi (dal comportamento individuale alle patologie non infettive e degenerative tipiche delle nostre società post-industriali).
È interessante ricordare che il frate moldavo si interessava di migliorare alcune specie di piante da lui coltivate e per poter far ciò necessitava di una più ampia comprensione dei meccanismi che stanno alla base dell’ibridazione (come allora veniva chiamata l’eredità).
Cancer in Children & Adults with Intellectual Disabilities: Current Research Aspects (Disability Studies: Cancer Etiology, Diagnosis and Treatments)
By Daniel Satgé and Joav Merrick
Nova Science Publishers Inc, 2011
In recent years, it has become clear that cancer is a major health concern for people with an intellectual disability. In the general population it is estimated that one in four people will develop cancer and that more than half of those diagnosed will die from the disease. Recent research has revealed that cancer is not less frequent in people with an intellectual disability and some tumours are more common. This population has different risk factors for developing cancer and different needs for both medical and psychosocial care provision. Consequently, medical surveillance, diagnosis procedures and treatments often have to be modified to suit this population. This book presents and discusses research on topics such as adapted care for people with intellectual disability and cancer, general aspects of cancer surveillance, cancer in persons with Down syndrome and also cancer in persons with other syndromes.
The wisdom of the body: future techniques and approaches to morphogenetic fields in regenerative medicine, developmental biology and cancer, by M. Levin (Regen. Med. (2011) 6(6), 667–673). “This article discusses an unconventional perspective: morphogenetic fields (information-bearing global patterns in chemico-electrical properties that guide growth and form) as a profound unifying concept central to biology and medicine”. Indeed, this paper address some relevant, even generally neglected issues in different field of biology and medicine: chronic degenerative pathologies, cancer, developmental processes as well as inborn errors. The key central argumentation lies on the “strategic” role played by biophysical cues in driving biological functions. Such forces are entangled into the “field”, to which cells and tissues belong, and contribute in shaping its boundaries. The integrity of such field is needed in order to maintain the correct patterning of tissues and organs . “This means we must learn to understand the key aspects of the morphogenetic field that controls pattern formation, including its biochemical, bioelectrical, physical and planar polarity aspects”. This kind of argumentation are in support of a new paradigm in biology research, suggesting how inadequate the current theoretical, gene-based, framework is. We are looking forwards how and when that approach might foster new insights and contribution in the field of carcinogenesis.