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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The problem of a relationship between nutrition and cancer has to be approached from two different points of view: 1. Direct effect of carcinogens present in foods or in food additives (direct carcinogenesis), 2. In-vivo synthesis of carcinogens caused by changes in metabolism due to altered dietary habits (indirect carcinogenesis). For the second mechanism, we have to make a distinction between the effects of nutritional deficiency and of nutritional excess. Some examples from animal experiments are presented. In man, possible relationships between nutrition and cancer are postulated mainly for tumors of the gastrointestinal tract and recently also for hormone-dependent cancers. Epidemiological evidence points to the major importance of the indirect way of carcinogenesis caused by specific nutritional deficiencies and excesses. Experimental studies in man are difficult to perform. Therefore, most hypotheses are based on statistical associations, and great caution is required in drawing inferences on causal relationships. Cancers of the upper and lower gastrointestinal tract epidemiologically behave in a different way, the former showing a marked decrease in most western countries, the latter a slight increase. The etiology of the cancers of the esophagus and stomach has still to be determined in spite of many hypotheses. Migrant studies show a major effect of environmental rather than genetic factors. Substantial differences in dietary habits between countries with high and low incidence of stomach cancer (Japan and United States) point to the importance of nutrition as an etiological factor with a high probability, but no specific dietary components have been identified so far. The same is true for cancer of the large bowel. Recent hypotheses suggest that dietary factors may relate to cancer of the colon by their effect on bile production and on the bacterial makeup of faeces which in turn might be transforming bile acids into active carcinogens. There is, however, disagreement about the specific dietary component responsible for this model of carcinogenesis. BURKITT stresses the importance of the lower consumption of dietary fiber, resulting in retarded bowel function and additional time for bacterial proliferation and degradation by bacteria of bile acids. WYNDER, on the other hand, explains the increased bile acid and neutral sterol excretion and microbial modification of these compounds with the high content of animal fat in the western diet. With hormone-dependent cancers (breast, endometrium, ovary, prostate), a correlation has been shown between body weight and height and breast cancer as well as between overweight and cancer of the endometrium. Which aspect of diet, if any, is responsible for changes in hormone metabolism, resulting in an increased risk of these cancers, is still to be proved. On the basis of current knowledge, it is extremely difficult to draw inferences for preventive action. Certainly, a cancer-preventing diet cannot be established...
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PMID:[Nutrition and cancer (author's transl)]. 101 38

Colorectal cancer is the third most common malignant neoplasm worldwide. Epidemiological and laboratory animal studies have established a link between various nutritional factors and the etiology of this cancer. Recent studies in genetic epidemiology and molecular biology have shown that inherited genetic factors also play an important role in colorectal carcinogenesis. Thus, genetic-nutritional interactions may form the basis for the development of this cancer. Nutritional factors that appear to promote or attenuate the carcinogenic process in the colon include fat, excess calories, fibre, calcium, selenium, and various vitamins. Strategies for primary prevention of colorectal cancer should therefore be targeted to all populations who are at risk because of dietary and hereditary predisposition. Based on current knowledge, recommended nutrition guidelines for reducing the risk of colon cancer include decreased fat consumption, adequate amounts of fruits, vegetables, and calcium, and avoidance of overweight. Research to further elucidate the role of diet in colorectal carcinogenesis should include randomized studies in humans, testing of various nutritional regimens, and the use of colonic adenomas and markers of cell proliferation and differentiation as end-points.
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PMID:Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer. 220 51

From an overview of epidemiological evidence on nutrition, diet and cancers of the breast, endometrium and ovary, the following indications can be drawn: Overweight and obesity are causally related to endometrial and post-menopausal breast cancer, and may account for as much as one third of the cases of endometrial and one tenth of breast cancer in Europe. It is not known whether obesity or overweight early in life has any role on breast cancer risk, nor whether obesity influences ovarian carcinogenesis. Overweight tends to be associated with an unfavourable prognosis for breast cancer. Despite extensive research, the available knowledge on diet and breast cancer is largely inconsistent, and the results from ecological and individual-based studies are contradictory in relation to fat, proteins, total energy, alcohol, etc. There are only scanty data on diet and endometrial or ovarian cancer, which tend to suggest role for fat (or animal fat) in the risk of these neoplasms. The evidence on diet and breast, ovarian and endometrial carcinogenesis is still too scanty or inconsistent to be of any practical preventive value. Thus, the only clear indication for prevention is that a reduction of overweight would avoid a substantial number of cases of endometrial and post-menopausal breast cancer.
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PMID:Nutritional factors and cancers of the breast, endometrium and ovary. 269 10

Consulting toxicologists began in 1982 to question the use and potential involvement of oil gavage test-compound administration in unexpected NTP carcinogenesis responses. Investigations have focused on corn oil gavage alternatives, vehicle type and volume, alteration of MTD, teratogenic effects, disposition of test compounds, and target tissues. Micoencapsulation will require considerable development research to make it a suitable alternative. Vehicle type and volume appear to have different effects on the apparent MTD, teratogenicity and disposition of very similar compounds. Only two tissue effects have been observed in the NTP oil gavage bioassay data. First, there is a sporadic and weak association with exocrine pancreatic acinar cell proliferative lesions; these lesions are highly correlated with overweight male Fischer 344/N rats. Second, leukemia is reduced about 50 percent in the male Fischer 344/N rats; this is a strong association which results in an 8-10 percent increase in survival. The protective effect of corn oil gavage is remarkable and there is no significant enhancement of tumor development. Corn oil gavage under the conditions of the NTP carcinogenesis bioassay does contribute to overnutrition and undesirable increased body weight, especially in male Fischer 344/N rats. The NTP and NCTR research programs include research plans to address critical oil gavage, diet composition feeding regimen, exercise and hormonal status questions. Results of these studies will point the way to improving long-term carcinogenesis and toxicity testing.
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PMID:Oil gavage test-compound administration effects in NTP carcinogenesis-toxicity testing. 309 53

Overweight, lipidemia features, glucose tolerance and insulinemia were studied in 642 females suffering tumors of the corpus uteri, breast, ovary and large bowel, i.e. types of neoplasia which often occur and correspond to the syndrome of primary multiple "hormone-related" cancers. Beside certain obvious similarities in the said parameters established among patients with the said pathologies, the distinctions related, first of all, to degree of pernicious tumor process and, possibly, preoperative weight loss. Since no differences were found in manifestations of hormono-metabolic disturbances between cases of solitary and primary multiple neoplasms of the same localizations, it is suggested that carcinogenesis of both types might be caused by the same factors.
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PMID:[Specifics of metabolic disorders in patients with "hormone-associated neoplastic" syndromes]. 880 40

Atherosclerosis and carcinogenesis may share some common mechanisms of the genotoxic action of exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs). The main objective of this study was to test the hypothesis that "bulky" aromatic DNA-adducts in smooth muscle cells (SMCs) of thoracic aortas taken at autopsy from sudden and accidental death male subjects, aged between 30 and 60 years (N=133), are associated with the stage of atherosclerosis. The subjects with severe atherosclerotic damage were treated as "Cases" (N=66). The subjects meeting diagnostic criteria for slight and moderate total atherosclerotic body damage were treated as "Controls" (N=67). An additional objective of the study was to evaluate the effect of known atherogenic risk factors and possible modifiers of atherosclerotic changes, such as age, smoking, plasma lipid and antioxidant vitamin levels and some genetic susceptibility markers, e.g. polymorphisms of GSTM1, GSTT1, NAT2, CYP1A1 or apolipoprotein E (APO E) genes. We found significantly higher DNA-adduct levels in "Cases" as compared with "Controls" (2.11+/-1.07 adducts/10(8) nucleotides versus 1.49+/-0.55 adducts/10(8) nucleotides, P<0.001). "Cases" were significantly older and had elevated heart weight and plasma cholesterol levels and a higher frequency of overweight subjects as compared with "Controls". No significant differences in DNA-adduct levels between smokers and non-smokers within either group were detected. Multivariate logistic regression revealed that the "bulky" aromatic DNA-adducts, which are the most likely related to environmental exposure to genotoxic chemicals, remain a statistically significant predictor of the stage of atherosclerosis (OR=3.76, 95% CI=1.54-9.18, P=0.004) even after adjustment for age, smoking, obesity, heart weight and genetic susceptibility markers (GSTT1 and CYP1A1-MspI polymorphisms) that were also significant predictors. The fact that the "bulky" aromatic DNA-adduct levels predict the progression of atherosclerosis independently of smoking indicates that the formation of atherosclerotic plaques may also be initiated by environmental exposures other than tobacco smoke.
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PMID:DNA-adducts and atherosclerosis: a study of accidental and sudden death males in the Czech Republic. 1193 43

Endogenous hormones may play a role in ovarian carcinogenesis. Postmenopausal obesity, although associated with higher circulating levels of estrogen and androgens, has not been linked consistently to ovarian cancer. The present study examined the relationship between body mass index (BMI), height, and ovarian cancer mortality among postmenopausal women in a large prospective mortality study of 300,537 women who were cancer free at enrollment in 1982 and had no history of hysterectomy or ovarian surgery. During 16 years of follow-up, 1,511 deaths occurred from ovarian cancer. Cox proportional hazard modeling was used to compute rate ratios (RRs) and to adjust for confounders. Ovarian cancer mortality rates were higher among overweight [BMI >/=25;RR, 1.16; 95% confidence interval (CI), 1.04-1.30] and obese women (BMI >/=30; RR, 1.26; 95% CI, 1.07-1.48) compared with women with BMI <25. Use of postmenopausal estrogens modified the association between BMI and ovarian cancer mortality (P = 0.05). The increased risk associated with obesity (BMI >/=30) was limited to women who never used postmenopausal estrogens (RR, 1.36; 95% CI, 1.12-1.66) and was not seen among ever users (RR, 0.93; 95% CI, 0.62-1.41). Height was positively associated with ovarian cancer mortality. Compared with women 152-156 cm tall, ovarian cancer mortality rates were lowest for the shortest women (RR, 0.72; 95% CI, 0.47-1.10 for women <152 cm) and highest for the tallest (RR, 1.41; 95% CI, 0.95-2.09 for women >/=177 cm). In this study, obesity and height appear to be independently associated with ovarian cancer mortality. The 36% increase in risk associated with obesity among women who had never used postmenopausal estrogens may have important public health implications because obesity is a growing problem in the United States.
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PMID:Body mass index, height, and the risk of ovarian cancer mortality in a prospective cohort of postmenopausal women. 1222 25

Epidemiologic studies suggest that intake of high energy from fat, inducing overweight, increases the risk of cancer development and promotes colon carcinogenesis. It is therefore important to understand which parameters are affected early on by a high-fat diet in order to devise and improve protective nutritional strategies. We investigated the effect of high energy/fat intake on colon mucosa of male Wistar rats induced by a single 1,2-dimethylhydrazine (DMH) injection. Aberrant crypt foci (ACF) were numbered and modifications in cyclooxygenase-2 (COX-2) and beta-catenin levels assessed. Peroxisome proliferator- and retinoic acid-activated receptors (PPAR and RAR, RXR) are key transcription factors regulating gene expression in response to nutrient-activated signals. A short-term study was designed to evaluate whether alterations in mRNA expression of nuclear receptors can be detected at the beginning of the weight gain phase induced by an appetizing hyperlipidic diet (HLD). HLD consumption induced early downregulation of PPARgamma (-33.1%) and RARbeta (-53.1%) mRNA expression concomitant with an increase in levels of COX-2 (+45.5%) and beta-catenin (+84.56%) and in the number of ACF (191.56 +/- 88.60 vs. 21.14 +/- 11.64, p < 0.05). These findings suggest that HLD increases ACF occurrence, possibly through alterations in the mRNA expression profile of nuclear receptors. Moreover, the use HLD rich in retinyl esters or supplemented with all-trans retinoic acid led to a reduction in the number of ACF. Vitamin A also prevented HLD-induced alterations and the increase in levels of COX-2 and beta-catenin. The present observations show a protective role for vitamin A against disturbances associated with HLD exposure in induced colon carcinogenesis.
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PMID:A high-fat diet generates alterations in nuclear receptor expression: prevention by vitamin A and links with cyclooxygenase-2 and beta-catenin. 1585 52

In vitro and animal studies indicate that vitamin D may have anti-cancer benefits, including against progression and metastasis, against a wide spectrum of cancers. Supporting an anti-cancer effect of vitamin D is the ability of many cells to convert 25(OH)D, the primary circulating form of vitamin D, into 1,25(OH)2D, the most active form of this vitamin. No epidemiologic studies have directly measured vitamin D concentrations or intakes on risk of total cancer incidence or mortality. However, higher rates of total cancer mortality in regions with less UV-B radiation, and among African-Americans and overweight and obese people, each associated with lower circulating vitamin D, are compatible with a benefit of vitamin D on mortality. In addition, poorer survival from cancer in individuals diagnosed in the months when vitamin D levels are lowest suggests a benefit of vitamin D against late stages of carcinogenesis. The only individual cancer sites that have been examined directly in relation to vitamin D status are colorectal, prostate and breast cancers. For breast cancer, some data are promising for a benefit from vitamin D but are far too sparse to support a conclusion. The evidence that higher 25(OH)D levels through increased sunlight exposure or dietary or supplement intake inhibit colorectal carcinogenesis is substantial. The biologic evidence for an anti-cancer role of 25(OH)D is also strong for prostate cancer, but the epidemiologic data have not been supportive. Although not entirely consistent, some studies suggest that higher circulating 1,25(OH)2D may be more important than 25(OH)D for protection against aggressive, poorly-differentiated prostate cancer. A possible explanation for these divergent results is that unlike colorectal tumors, prostate cancers lose the ability to hydroxylate 25(OH)D to 1,25(OH)2D, and thus may rely on the circulation as the main source of 1,25(OH)2D. The suppression of circulating 1,25(OH)2D levels by calcium intake could explain why higher calcium and milk intakes appear to increase risk of advanced prostate cancer. Given the potential benefits from vitamin D, further research should be a priority.
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PMID:The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). 1586 50

The classical view according to which overweight/obesity is related to cancer considers adipose tissue as an active and metabolic "organ", acting through endocrine, autocrine and paracrine processes. Consequently, it has been hypothesized, that genesis and progression of cancer may be caused by different biological factors acting through diverse mechanisms including changes in the synthesis and bioavailability of sex hormones, insulin resistance, release of growth factors and/or proinflammatory cytokines and abnormal energetic disposal and expenditure. We have shown that overweight/obesity can be experimentally induced by benzo[a]pyrene, a universal well characterized chemical pollutant and that overweight/obesity may in fact be caused by several types of chemical pollutants. In this paper we propose that in addition to the above hypothetical biological mechanisms, adipose tissue acts as a reservoir for lipophilic, liposoluble environmental carcinogens, so that chemical pollution may in fact generate both overweight/obesity and cancer. More precisely, we propose that many carcinogens, be they mutagens or promotors can be stored in the adipose tissue, be released at convenient dose in the blood circulation and therefore target peripheral tissues to induce carcinogenesis. Such carcinogens mainly include organochlorine pesticides and PCBs. Their association with an increased risk of cancer seems to be demonstrated for breast and prostate carcinoma, as well as for lymphoma, not only in obese patients, but also in normal weight or even leaner patients suggesting that the adipose tissue may act as a reservoir for environmental carcinogens in obese as well as in non-obese patients.
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PMID:Overweight/obesity and cancer genesis: more than a biological link. 1803 14


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