added an update
COBALAMIN AND CANCER
Results from intervention trials of β-carotene, α-tocopherol, and vitamin A (eg, CARET and ATBC 1) have brought much adverse publicity for vitamins and nutritional supplements. Parties with a vested interest have jumped on board, clamouring for bans and legislation. But no one has questioned the fundamental premise of these trials—namely, that vitamins are being tested and treated as if they were drugs. This paradigm is misguided and largely accounts for the conclusions of the recent trials.
NO ABSTRACT. Introduction: “Multiple myeloma is incurable”, the textbooks tell us.(1, 2) Median survival depends on the stage at diagnosis and can range from six months to five years.(3) Long term survival is virtually unknown, but not quite. The 1992 survival curve for an unselected series of 156 patients at St Bartholomew's Hospital shows a 2.5% survival at 10 years.(4) A much earlier study at the Mayo Clinic, covering 870 cases, found a not dissimilar total survival rate at 10 years of 2.2%, with a 3% survival for those 597 patients diagnosed in the 1964 onwards, ...
NO ABSTRACT: Introduction The aetiology of Multiple Myeloma is generally acknowledged as obscure. (1) The epidemiology presents a number of puzzles. Most cancers are the affliction of age. Myeloma is more remarkably so, with few cases under the age of 40, (0.3% under 30), 98% above this demarcation line and a median incidence age of 65 years. (2) (Figure I). Whilst sporadic community(3) and familial(4,5) clusters have occurred, - and indeed, even husband and wife cases(6,7), - to date no evidence of genetic predisposition has been discovered(5), and failure to find a definitive environmental cause for the community clusters might suggest that such cases are simply random, given the statistical low incidence relative to Myeloma incidence in general.(3,7) Myeloma also affects more men than women, more blacks than whites, at a relatively earlier age than whites, and farmers more than the general population. (8) A French study noted a 40% excess prevalence, age- and sex-adjusted, amongst farmers, relative to other occupations.(9) Other at-risk groups include foresters(8), fishermen(8), veterinarians (10), teachers(11), anaesthesiologists(12), radiologists, and anyone exposed to ionising radiation.(8) Though the latter would seem an obvious risk factor, intriguingly the proportion of atom bomb victims at Hiroshima and Nagasaki who ultimately developed Myeloma seems relatively small, if still significant.(8) Indeed, Myeloma is a rare cancer, accounting for no more than 1% of all cancers, and 10% of all haematopoietic malignancies(2), although its incidence, as with the majority of all cancers, is on the increase.
NO ABSTRACT> Introduction:The etiology of Multiple Myeloma is generally acknowledged as obscure . The epidemiology presents a number of puzzles. Most cancers are the affliction of age. Myeloma is more remarkably so, with few cases under the age of 40, (0.3% under 30), 98% above this demarcation line and a median incidence age of 65 years[2 ]. Whilst sporadic community  and familial [4,5] clusters have occurred, and indeed, even husband and wife cases,[6,7] to date no evidence of genetic predisposition has been discovered . Failure to find a definitive environmental cause for the community clusters might suggest that such cases are simply random, given their statistical low incidence relative to Myeloma incidence in general [3,7]. Myeloma also affects more men than women, more blacks than whites and at a relatively earlier age than whites, farmers more than the general population . A French study noted a 40% excess prevalence, age- and sex-adjusted, amongst farmers, relative to other occupations . Other at-risk groups include foresters [8,] fishermen , veterinarians, teachers, anaesthesiologists , radiologists, and anyone exposed to ionizing radiation . Though the latter would seem an obvious risk factor, intriguingly the pro- portion of atom bomb victims at Hiroshima and Nagasaki who ultimately developed Myeloma seems relatively small, if still significant . Indeed, Myeloma is a rare cancer, accounting for no more than 1% of all cancers, and 10% of all haematopoietic malignancies , although its incidence, as with the majority of all cancers, is on the increase. It now appears that Multiple Myeloma, though a B cell malignancy, very much conforms to what we know about the mo- lecular biology of solid tumours, even down to the development of angiogenesis, albeit in the marrow . The oncogenesis of Myeloma takes place over several decades in the largely silent, pre-cancer condition known as Monoclonal Gammopathy of Unknown Significance (MGUS), where the clonal plasma cells are immortalized but not transformed. About 24% of people with MGUS go on to develop full blown Multi- ple Myeloma and/or other lympho-prolif- erative malignancy . MGUS and pre-Stage I Myeloma are relatively indolent, benevolent phases. Paradoxically, however, once in the active phase, Myeloma is lethal and without a known cure, with the exception of allogeneic transplants which carry a 41% mortality rate . Moreover, paradoxes and problems abound in the pathology and treatment of Myeloma, a mystifyingly heterogenous disease, with survivals recorded ranging from a few months to nearly two decades . Con- ventional chemotherapy offers a median survival of 18 months to 2 years. Newer approaches of high-dose combination chemotherapy and autologous stem cell transplant have demonstrated an improved median survival of 3 to 4 years, with 20% alive at 5 years. Improvement is pertinent largely to a minority of patients who fit particular diagnostic criteria, including age less than 56 years, low ß2 microglobulin, low C-Reactive Protein, no deletion of chromosome 13 and a low Labeling Index . Myeloma, in fact, presents a therapeutic enigma. It does not respond to therapy as cancers generally do . It does not exhibit a dose-response effect; remission duration and survival does not appear directly re- lated to Myeloma cell-kill; maintenance therapy does not necessarily prolong remission and survival duration; surviving Myeloma cells do not necessarily begin to grow and proliferate exponentially when treatment stops; and treatment can lower the M-protein to a plateau beyond which it will not fall lower despite continued therapy. Finally, in the rare cases where longterm survival is achieved beyond ten years, there is also the paradox that, alone of all hae- matopoietic malignancies, such longterm survival does not equal cure, and relapse is still, bafflingly, the rule . Why? Why too, for instance, should Myeloma show “a special predilection for the spinal column”? Again, the mysterious, rare but recognized phenomenon of the plateau achieved without treatment, peculiar to Myeloma, in which the disease is still present but “spontaneously” becomes inactive , suggests an inner mechanism of control. If we knew what this mechanism involved, we might be able to access it and perhaps prolong the plateau indefinitely, as good as a cure. Similarly, in a tiny minority, about 4%,20 MGUS occasionally disappears altogether. If we knew why, as Robert Kyle has remarked, “If we could reverse MGUS, we could cure Myeloma.” .