NITROSOGENESIS OF SKIN (HUMAN) CANCER- THE HIDDEN TRUTH OF A NEVERENDING STORY: NITROSAMINE CONTAMINATION IN OLMESARTAN, VALSARTAN AND HCT AS MAIN RISK FACTOR FOR THE DEVELOPMENT OF KERATINOCYTE CANCER.

The pathogenesis of skin cancer remains shrouded in mystery. Nevertheless, a substantial amount of new data is now available to provide a logical explanation regarding the possible link between 1) the occurrence of single or multiple acquired/somatic mutations and 2) the generation and progression of skin cancer, as well as 3) the potential association of the above two facts with the availability of nitrosamines in drugs for hypertension, diabetes, gastritis, acne, tuberculosis, various other antibiotics, etc. The nitrosogenesis of skin cancer is slowly but surely being established as a significant concept that could not be ignored for longer periods of time. It should only be analysed in detail with a view to future prevention for the benefit of public health. The nitrosogenesis of skin cancer is slowly but surely being established as a significant concept that cannot be ignored for longer periods of time. It should only be analysed in detail with a view to future prevention for the benefit of public health. Although this information has been known for decades (but in relation to the development of other cancers), there is still no comparative analysis of the mutations that occur after ingestion of a particular mutagen, also known as nitrosamine. This analysis could to some extent highlight/support or reject to some extent the thesis of the role of nitrosamines and genetic instability leading to the subsequent generation of a malignant cell clone. The notion of skin cancer nitrosogenesis should become a priority concept very soon, but it should also become an evidential memory, a byword, and an equivalent of the ignorance with which modern civilization has treated its own health for decades within the processes of globalization. It is these processes that include nitrosamines as a major component of the "medicinal and nutritional menu" of patients. It remains unclear at present why regulatory authorities are making endless attempts to legalise the availability of a number of mutagens/human carcinogens in the most commonly distributed medicines worldwide. And to persuade "others" that there is no risk from their permanent, controlled and long-term intake. The newly introduced regulatory norms in practice concern the potential/permissive availability of nitrosamines in a serious number of drugs: drugs with radically different mechanisms of action such as: ranitidine, metformin, ACE inhibitors, beta blockers, thiazide diuretics, sartans, rifampicin, but also probably a number of others. However, the occurrence of identical, similar patterns of cancers (skin cancers) following their administration (after ingestion of different classes of drugs) makes the ubiquitous permissive availability of nitrosamines (in each class of these drugs) the most potent and most likely pathogenetic inducer of cancer. These comparative patterns of skin tumor occurrence should have even stronger evidentiary value than even so-called prospective follow-ups. Nitrosamines are and remain one of the best studied mutagens/carcinogens that can alter/modify the human genome. A fact underlined repeatedly over the years (also based on in vivo data, repeatedly ignored) and a fact that, according to the literature, concerns mainly tire industry workers (British rubber workers). It is in this category of patients and after exposure to high doses of nitrosamines (potential inhalation intake) that high mortality has been found in bladder, lung, stomach, oesophageal cancer, multiple myeloma, leukaemia, prostate cancer, pancreatic cancer, and liver cancer. Similar international observations (in vivo/Sweden) concerning intensive human exposure (Swedish rubber workers) to high doses of nitrosamines in a working atmosphere (inhalation type of carcinogen uptake) emphasize the resulting direct subsequent risk of other alarming symptoms such as: nasal bleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and altered levels of eosinophils and total immunoglobulin G (IgG), compared with unexposed patients. The neglect of these important observations over the years has led to the ubiquitous and currently difficult to counteract and unpunished prevalence of nitrosamines in even the most commonly distributed drugs worldwide (except in the food industry). It is precisely because of this fact that it should come as no surprise to anyone that there is new evidence of an avalanche in the number of new cancers after ingestion of potentially nitrosamine-contaminated preparations. Skin cancer could be seen in the near future precisely as a model of a side reaction after application or long-term contact with mutagens called nitrosamines. Based on the above, and wishing to add to the worldwide data on the heterogeneous cancers that occur after contact with nitrosamines, we draw the attention of the scientific community to the risk of developing keratinocytic cancer after ingestion of nitrosamine-contaminated drugs: sartans and thiazide diuretics. We believe that the role of the generic substance in these drugs could also contribute to some extent to the progression of an already present tumour branch, but this influence is rather minor and without significant clinical relevance. We present a patient who had been taking 2 sartans (valsartan/ olmesartan) over the years as monotherapy and in combination with hydrochlorothiazide, who developed over time and within this intake two forms of keratinocytic cancer: verrucous carcinoma and basal cell carcinoma. The focus of discussion concerns a newly introduced medical concept: nitrosogenesis of skin cancer. The detailed study of nitrosogenesis should be a major, primary task for regulators, researchers, clinicians, and pharmaceutical companies.