This action might not be possible to undo. Are you sure you want to continue?
Grant (BSc Msc PhD) New Deer, Scotland, UK AB53 6SX It is commonly believed that the origin of cancer is entirely due to defective genes i.e. the existence in susceptible individuals of defective DNA sequences. Perhaps a useful concept is that cancer is caused by an alteration of DNA caused by the effects of a cumulative effect of damage caused by environmental agents (carcinogens) such as those which are known to be present in cigarette smoke or atmospheric pollution, acting in concert with inherited procancer genes . Alteration of DNA may of course dramatically change in a harmful manner the activities of expressed proteins. A good diet contains antioxidants which can protect DNA against the mutagenic effects of toxic environmental pollutants, so a good diet is expected also to protect against pro-cancer effects of such pollutants (cf. e.g. S.P. Hussain, Nature Rev. Cancer, 2003, 3, 276-85). This sort of argument was behind the recent UK government’s publicity which advised subjects to eat five portions of vegetables per day. A contrary message regarding the potentially anti-cancer role of good diet has, however, recently been given by the results of a large (5000,000: 142605M, 335873F)) epidemiological population survey (EPIC). While early indications from this survey seemed initially to strongly support the anti-cancer effects of fruit and vegetable dietary advice (cf. BBC News 27 May 2002) the final report (P. Boffetta et al., J.Natl. Cancer Inst., 2010, doi:10.1093/jnci/djq072) indicated that eating fruit and vegetables had only a relatively minor effect on cancer death rates in the surveyed population (as indicated by press reports). This conclusion was however suggested to be misleading by a Cancer Research UK Science Update blog which pointed out that in the final EPIC study had actually shown that eating 2.5 portions of fruit and vegetables /day had been associated with a 3% lower risk of cancer compared to people who eat less than this amount, and those who eat 5 portions of fruit and vegetables/day had a 9% lower risk of cancer; furthermore those who eat more than 8 portions/day had a 11% lower risk. Nevertheless the statistical overall benefit of fruit and vegetables in diet to anti-cancer health benefit had been reduced considerably with the larger 500,000 sample compared the results of numerous smaller earlier surveys. This could indicate that regional differences between subgroups of the populations surveyed in the 500,000 sample which had not been identified might also contribute to the tendency for humans to die of cancer. [It should also be noted that the large survey however had successfully identified a sub-group of cancers victims who were put more at risk of this disease by being heavy alcohol drinkers and who benefited to a greater degree than others from the ingestion of fruit and vegetables]. Perhaps part of the reason for the apparent lack of a dramatic effect on the rate of deaths attributable to cancer of fruit and vegetables dietary intake in the majority of people in the large study, was the fact that toxic DNA-damaging substances can also inhibit cancer. An example of this is provided by the prominent anti-cancer drug cisplatin which is known to seriously damage DNA, but in an anti-cancer manner. The precise anti-cancer mechanism is however unknown but cisplatin was found in recent gene profiling studies to both up and down –regulate a consistent subset of genes (A.M. Galea & V. Murray, Cancer Informatics, 6, 1-41. Many scientifically sound studies had seemed to strongly suggest that dietary factors can have fairly direct both pro and anti cancer effects. E.g. eating fruit and vegetables everyday had been thought to have been well-established to considerably reduces the risk of cancer. But nitrite used as a preservative in some foods is pro cancer. Such pro-cancer factors had been estimated in 1984 (cf., I. Stipala, New Scientist,104 ,8) to cause a third of cancers worldwide but this proportion was greater in Japan which had the highest rates of death from cancers of the mouth pharynx, esophagus, stomach, lung and bladder. Other later surveys also showed pro-cancer effects of eating red meat (e.g. T. Norat et al., Int. J. Cancer 2002, 98, 241-256). It seems likely that β carotene, vitamin C and fibers in fruit and vegetable rich diets can inhibit cancer. However the pro-oxidant and pro-nitrant effects of excess iron ions e.g. under iron overload situations promoted by excessive consumption of red meat are able to create pro-cancer free radicals. Dietary meat can also putatively causes accumulation of a sugar (N-glycolylneuramic acid) which does not occur in adult humans (but its presence in tumours could suggest uptake from dietary sources such
as red meat and milk products and involvement of this sugar in the etiology of cancer, e.g. by the induction of a chronic pro-oxidant immune response) [cf., BBC News 29 Sept 2003, “red meat cancer threat”; cf. also A. Varki, Yearbook. Phys. Anthropol., 2002, 44, 54-69; Glycoconjugate J., 2009, 26 (3) 231-245; M. Hedlund et al., PNAS USA, 2008, 105 (48) 18936-18941] . Heparin, a drug which has been used for some seventy years was discovered many years ago to stimulate nuclear and chromatin transcription processes (S. Seki & T. Oda, Biochim..Biophys..Acta 1977,479, 391; B.E. Coupar & C.J. Chesterton et al., Eur. J.Biochem., 1977, 79, 525-33 (this action was attributed to the interaction of this polyanion with the histones which removes DNA template restriction and allows RNA synthesis). Heparin signalling is representative of the larger high system manager system of animal biology afforded by heparan sulphates, a system of different polysaccharide microstructures which occur a linear alternating copolymer of glucosamine with iduronic/ glucuronic acid. This information storage and processing system, which is somewhat analogous to, but, of course, highly distinct from DNA, contains (heparin-like) signals which are known to be centrally implicated in cellular control activities of putative central relevance to a fuller understanding of how environmental inputs which can promote or inhibit cancer. Indeed natural heparin-like molecules which circulate in the bloodstream may provide a natural anti-cancer (and anti-other degenerative disease) protection system (cf., H. Engleberg, Cancer (New York) 1999, 85, (23) 257-272 cf., Circulation, 1961, 23, 573-577; D.L. Ornstein & L.R. Zacharski, Haemostasis, 1999, 29, 48-60. [The amounts of these anti-cancer heparin like molecules are expected to vary with diet, and be higher with a high fruit and vegetable diet]. Platinum and other inorganic elements which have been used for anti-cancer therapy also bind to heparin. (cf., D.Grant et al.,Biochem. Soc. Trans., 1996, 24 (2) 204S). Indeed natural heparin contains minute amounts of Pt and Ga. The anti-cancer effect of heparin may therefore derive at least in part from this phenomenon. Further studies are needed to probe this possibility. Glycosaminoglycans in general also exhibit antioxidant capacity being able to prevent DNA fragmentation under oxidative stress (cf. GM Campo et al., Free Rad. Res. 2004, 38 (6) 601-611.
Some other ‘diet & cancer’ studies A study 884 of human subjects and controls by J Lin et al. of the University of Texas reported at the101st annual meeting in 2010 of the American Association for Cancer Research.(cf., Press Association e.g. the Guardian 19 April 2010, p15) reported from that cooking meat or fish at high temperatures increases the risk of cancer; this being attributed to the formation of heterocyclic amine carcinogens under these cooking conditions. There was a 48% greater risk of bladder cancer between the greatest and the least meat eaters in the survey. The occurrence of bladder cancer has also been traditionally associated with occupational exposure to heterocylic amines. A survey of recent studies of how such amines promote cancer is given by the National Cancer Institute Fact Sheet –“Heterocyclic amines in cooked meat” available at htttp://www.cancer.gov/cancertopics/factsheet/ …/heterocyclic-amines Sir D. King et al., in a UK government study The Foresight Report written by 250 leading scientists highlighted the danger to health of the global epidemic of obesity. 10% of all cancers in non-smokers is believed to be linked to obesity which is further believed to be related to diet. Obesity has also been linked to intoxication by globally distributed persistent organic pollutants (POPs) which become bio-concentrated in some fatty animal and some fish tissues as well as in some milk products. A vegetarian or vegan diet is commonly believed to be associated with a major decrease in cancer risk. This is well illustrated by historical comparisons between data from countries ranging between full Eastern and full Western-lifestyles cf. the graphics presented by William Harris M.D. in 1999 at www.vegsource.com/harris/cancer_vegdiet.htm, which shows how the incidence of cancers can be statistically associated with situations where meat and dairy food intake differ markedly. The
incidence of breast cancer might be assumed on the basis of these data, to have been boosted by the consumption in the Western lifestyle of some dairy products. The consumption of dairy products might then be assumed to be highly pro-cancer. Full fat dairy products are however sources of (anti-cancer) Vitamin D as well as of Vitamin A. Although there seemed to be little evidence of benefit to humans, it was indicated that Vitamin A prevented squamous cell cancers in laboratory animals (G. Kolata, Science, 1984, 223, 1161).
 The traditional view that genetic alterations are involved in many cancers. Oncogenes are homologous to normal genes; in viruses they are known to be able to cause animal cancers. Cultured animal cancer cells often carry transforming genes that can cause normal cells to acquire cancerous characteristics. Faulty control of normal cellular genes may underlie pro-cancer genetic transformation. Mutagenic chemicals and radiation damage DNA which is believed to be why they are carcinogenic. Simian sarcoma virus v-sis was found to show homology with platelet derived growth factor (PDGF) and c-sis transcripts and synthesis of PDGF-like proteins were detected in human osteosarcoma. It seemed that a general principle was emerging that cancer was the result of aberrant growth factor activities (cf., e.g. , D.G. Graves et al., Science, 1984, 226, 972-974). PDGF activities are also affected by heparan sulphate suggesting that this polysaccharide, e.g. if defective, could affect oncogene activities. Proto-oncogenes. pp60c src (protein tyrosine kinase encoded by c-src is abundant in brain etc. and not concerned with mitosis. This protein, however, undergoes a post-translational modification (not phosphyorylation) which greatly increases its activity. The modified form of pp60c-src found in neurons could be a functional analogue of v-src. v-src can meddle with differentiation (either blocking or reversing it). It is believed that phenotypes elicited by v-src and NGF are similar. L.A.MacMillan-Crow et al. reported (Arch. Biochem. Biophys., 2000, 377 (2) 350-6) that tyrosine nitration of c-src kinase occurs in human pancreatic ductal adenocarcinoma and that such nitration could likely boost tyrosine kinase signalling. This finding implicates the nitration of oncogene products as a possible key factor in the progression of cancer. It has often been assumed that tyrosine nitration is always a harmful effect, being a hallmark of any degenerative disease processes but S.W. Park et al., Mol. Cell. Proteomics, 2005, 4, 300-9, have indicated that tyrosine nitration of the p65 subunit of NF kappaB can rapidly inactivate nuclear factor kappa B associated pro-inflammatory (pro-cancer) processes. It is possible, however, that key roles may be played by certain dietary constituents which can act as anti-nitrants. These have not as yet been identified. Some clues about possible antinitrant chemical structures can be suggested by studies of seleniumcontaining molecules (e.g. ebselen (2-phenyl 1-2benzisoselenazol-3[2H]one}which may demonstrate therapeutic effectiveness against cancer (cf., V. Sharma et al., Int. J. Cancer, 2008, 123 (9) 2204-12;
R. Tewari et al., Mol. Oncol., 2009 3 (1) 77-83) e.g. by acting as pro-apoptotic agents which may in part be mediated via anti-nitrant effects. Nitrant overload could actually be of general importance to the induction of all degenerative diseases. A key target of nitrant overload may be the major animal polysaccharide glycosaminoglycan systems especially those afforded by heparan sulphate proteoglycans (cf., web.ukonline.co.uk/dgrant/dg4/; web.ukonline.co.uk/dg5/; [references for the foregoing sites are to be found at web.ukonline.co.uk/dg8/] cf., also web.ukonline.co.uk/dg2/ and www.scribd.com/doc/26994439/Publication-2-Web). In general a “correctly microstructured” heparan sulphate at cell surfaces and in extracellular matrices is anti-tumour. Excessive nitrosative stress seems to harm such heparan sulphate. The amounts of the non-sulphated glycosaminoglycan hyaluronan was found to be overexpressed in a variety of human malignancies being inversely correlated with survival rates. The production of such hyaluronan also seemed to be stimulated by the amounts of nitric oxide which cause pro-tumour extracellular matrix alterations (cf., P. Karihtala et al., J. Histochem. Cytochem., 2007 55 1191-9).