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Considering endometrial carcinoma as a natural experimental model for in vivo study of carcinogenesis, a hypothesis of endometrial type A carcinogenesis and some preventive prospects are advanced. Under the name of endometrial carcinoma two different types are considered: A) hormone dependent type, and B) autonomous type. Aging, obesity, hypertension and/or diabetes, persistent exposure to unopposed exogenous or endogenous estrogens are recognized epidemiological factors for endometrial carcinoma. Experimental and clinical studies have shown that in pregnancy associated with clinical conditions characterized by a compromised maternal circulation in the intervillous space, a state of true or relative hypoxia stimulates syncytial hyperplasia, as adaptive process, in order to increase the exchange area of the placenta. Vaginosonographic studies have shown in patients with endometrial thickness greater than or equal to 4 mm complex and atypical hyperplasia than endometrial carcinoma in a higher percentage than in patients with endometrial thickness less than 3 mm. It seems that hypoxia in endometrial thickness, greater than 3 mm promoted by estrogens, would be a supplementary proliferating factor. Immunological studies have shown, in patients with complex or atypical hyperplasia of the endometrium and/or endometrial carcinoma, a host immunological reaction (DTHS-reactivity test) to a pharmaceutical placental suspension, when injected intradermally. An extract prepared from placental suspension is also recognized in vitro, by patients' serum (Ouchterlony's technique). To conclude, hypoxic insult, as common pathophysiological factor in most predisposing diseases for endometrial cancer, leads to a persistent multicellular hyperplasia of the endometrium. Sometimes populations with an altered growth pattern develop.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothesis for endometrial carcinoma carcinogenesis. Preventive prospects. 828 9

Hormones play a major role in the aetiology of several of the commonest cancers worldwide, including cancers of the endometrium, breast and ovary in women and cancer of the prostate in men. It is likely that the main mechanisms by which hormones affect cancer risk are by controlling the rate of cell division, the differentiation of cells and the number of susceptible cells. Hormones have very marked effects on cell division in the endometrium; oestrogens stimulate mitosis whereas progestins oppose this effect. The risk for endometrial cancer increases with late menopause, oestrogen replacement therapy and obesity, and decreases with parity and oral contraceptive use; thus risk increases in proportion to the duration of exposure to oestrogens unopposed by progestins, probably because unopposed oestrogens stimulate endometrial cell division. The effects of hormones on breast epithelial cell division in non-pregnant women are much less clear-cut than their effects on the endometrium, but both oestrogens and progestins appear to stimulate mitosis. Breast cancer risk increases with early menarche, late menopause and oestrogen replacement therapy, probably due to increased exposure of the breasts to oestrogen and/or progesterone. Early first pregnancy and multiparity reduce the risk for breast cancer, probably due to the hormonally-induced differentiation of breast cells and the corresponding reduction in the number of susceptible cells. Hormones do not have marked direct effects on the epithelial cells covering the ovaries, but hormones stimulate ovulation which is followed by cell division during repair of the epithelium. Risk for ovarian cancer increases with late menopause and decreases with parity and oral contraceptive use, suggesting that the lifetime number of ovulations may be a determinant of risk. For all three of these cancers risk changes within a few years of changes in exposure to sex hormones and some of the changes in risk persist for many years, indicating that hormones can affect both early and late stages of carcinogenesis. Understanding of the role of sex hormones in the aetiology of prostate cancer and of some rarer cancers is less complete.
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PMID:Hormones and cancer in humans. 853 37

The high incidence of breast cancer in Western women has been linked to nutritional factors such as high-fat/low-fibre diet, obesity and timing of weight gain. A mechanism is postulated through which the Western diet could act in conjunction with inadequate exercise and excessive weight gain at the time of a major change in hormonal balance. All these factors favour the manifestation of insulin resistance, and the concomitants of hyperinsulinaemia might then synergise with oestrogen in promoting the development of breast cancer. The mechanism is compatible with the 'breast tissue age' model of mammary carcinogenesis. The concomitants of hyperinsulinaemia could also influence the growth of established disease subsequent to its promotion, and it is suggested that the hypothesis be tested by an adjuvant randomised trial of a high-fibre/low-fat diet in patients following primary surgery for early breast cancer. It has been suggested that the development of insulin resistance may link the Western lifestyle not only to an increased risk of hypertension and arteriosclerosis, but also to increased breast cancer risk. Large abdominal fat deposits in women are frequently a marker of the presence of insulin resistance and are generally associated with an increased level of bio-available oestrogen. There is evidence that predominantly abdominal distribution of fat in women may be a marker of increased breast cancer risk from puberty onwards. Abdominal obesity may however be hidden, and it is more reliably demonstrated by imaging techniques such as CAT or MRI scans, than by anthropometric measurements such as increased waist-to-hip ratio.
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PMID:Obesity and breast cancer. 869 16

Epidemiologic evidence on the relation between nutrition and prostate cancer is reviewed. Little is known about the etiology of prostate cancer, despite its prominence as the leading cancer among men in the United States. Rational mechanisms for dietary influences on prostate carcinogenesis, including effects on production or metabolism of androgenic hormones, have been proposed, but because few suitable animal models have been developed, the laboratory literature on diet and prostate cancer is sparse. Despite strong ecologic data and largely consistent case-control and cohort data on dietary fat and prostate cancer, the role of this nutrient remains unclear. Few studies, to date, have adjusted the results for caloric intake, and no particular fat component has been consistently implicated. A notable finding is a strong positive association with intake of animal products, especially red meats, but this in itself does not specifically implicate fat. Epidemiologic investigations on vitamin A and carotenoids are divided almost equally between studies showing positive and inverse associations. The evidence from these studies for a protective effect of fruits and vegetables on prostate cancer, unlike many other cancer sites, is not convincing. The data on other dietary components that have been examined with regard to prostate cancer etiology (cadmium, zinc, vitamins C and D, beverages, and legumes) are too incomplete at this time to draw any inferences as to their importance. The evidence for anthropometric associations with prostate cancer is weak. Whereas a clear association with obesity has not been shown, a positive relationship to muscle mass, though not yet established conclusively, further suggests the importance of androgens in this cancer.
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PMID:Nutrition and prostate cancer. 885 Apr 37

Carcinomas of the gastrointestinal tract (GI) are among the most common malignancies with regard to their incidence and mortality. Nutritional factors play an important role in the tumor development. The strength of their influence varies with the localization in the GI tract. Epidemiological studies focusing on GI cancer incidence or mortality as an endpoint necessitate large numbers of subjects to achieve significant results. Generally, a low energy and fat intake and a high intake of antioxidative vitamins (vitamin C, E, beta-carotene) and secondary plant metabolites (especially polyphenols) appear to be protective in GI carcinogenesis. Moderate drinking of alcohol and increased consumption of whole grain products, as opposed to highly refined carbohydrates, may help to reduce the risk of colon cancer. The recommended type of diet is low in fat, especially in saturated fatty acids, includes monounsaturated fatty acids, and includes moderate amounts of polyunsaturated fatty acids (no more than 10% of calories). Moderate consumption of salt and of highly salted, smoked, and barbecued foods should be encouraged. Obesity should be avoided by trying to match energy intake with expenditure while increasing physical activity levels. The mechanisms by which nutritional factors act especially on molecular events still remain to be examined. The use of molecular biomarkers will help us better understand cancer development as well as the role and significance of nutritional factors in this process.
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PMID:Basis and consequences of primary and secondary prevention of gastrointestinal tumors. 889 41

Epidemiologic evidence in humans and controlled trials in animal models indicate that total dietary fat increases the risk of cancer. The animal evidence indicates that the greatest efficacy in promoting carcinogenesis is achieved with omega-6 fatty acids with little or no effect from either the omega-3 or monounsaturated fatty acid families. Epidemiologic studies in humans indicate a positive association between meat intake and colon cancer, but a negative association with chicken and fish. There is also a negative association between non-steroidal anti-inflammatory drug (NSAID) intake and colon cancer. Red meat is a potentially significant source of dietary arachidonic acid, which is the primary substrate for the eicosanoids whose production is blocked by NSAIDs. Thus there is a positive association between carcinogenesis and dietary intake of both the omega-6 fatty acid precursor linoleic acid and its product arachidonic acid, and a negative association with use of a drug blocking its metabolism to eicosanoids. Another potentially important factor in arachidonate metabolism is variation in its endogenous distribution. We have recently reported abnormal distribution of arachidonic acid between lipid fractions in human obesity, and parallel abnormalities in animal models of genetic obesity. This implies a potential role for variation in the endogenous distribution of arachidonic acid in the etiology of cancers which have increased incidence in human obesity. This paper addresses the role of arachidonate intake, its endogenous production, and its distribution within lipid fractions in carcinogenesis.
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PMID:Metabolism of exogenous and endogenous arachidonic acid in cancer. 893 50

Three perspectives on the integration of experimental and epidemiologic research on diet, anthropometry and breast cancer are presented. 1) Although body weight and height have been linked to breast cancer risk by epidemiologic research, their roles have not been directly explored with animal models. However, basic, clinical and epidemiologic research on obesity and associated metabolic alterations may be pertinent. Individual differences in the timing and magnitude of weight gain and loss during adult life need to be considered in epidemiologic studies of adiposity and breast cancer, along with individual differences in the pattern of body fat deposition, the hormonal and metabolic changes that accompany the adiposity, and family history of obesity-related chronic diseases. Animal models with genetic predispositions to obesity, diabetes and breast cancer merit further exploration, as well as models that can evaluate exposures occurring after puberty. 2) The synergy between experimental and epidemiologic studies on fat and energy intake and breast carcinogenesis has been productive because each discipline has had to incorporate recent findings of the other. Dietary studies utilizing animals with different genetic profiles are promising, but require identification of the critical genes in human carcinogenesis. 3) Controlled dietary intervention studies with human participants using intermediate endpoints can bridge the gap between animal and epidemiologic studies, but generally accepted intermediate endpoints for breast cancer need to be developed. Such studies would permit better control of diet than large clinical trials and the opportunity to explore mechanisms.
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PMID:Perspectives on integrating experimental and epidemiologic research on diet, anthropometry and breast cancer. 916 68

Using data from the Health Professionals Follow-Up Study, we prospectively examined the relationships between height, body mass index, waist and hip circumferences, and risk of total and advanced (extraprostatic and metastatic) prostate cancer. In addition, we assessed adiposity during childhood, adolescence, and early, middle, and late adulthood using pictograms in relation to prostate cancer risk. Between 1986 and 1994, 1,369 cases of prostate cancer (excluding stage A1) were confirmed in 47,781 men. Adult body mass index and waist and hip circumferences were not appreciably related to risk of total prostate cancer or advanced prostate cancer. In contrast, preadult (age 10) obesity assessed in 33,336 men in 1988 was prospectively related to lower risk of advanced [relative risk (RR) = 0.72 with 95% confidence interval (CI) = 0.47-1.10, between high and low quintiles; P(trend) = 0.06] and metastatic prostate cancer (RR = 0.38 with 95% CI = 0.19-0.77; P(trend) = 0.004). For the advanced lesions, an association was observed with height (RR = 1.68 with 95% CI = 1.16-2.43 for men 74 inches or taller, relative to men 68 inches or shorter; P(trend) = 0.01). In an analysis limited to particularly aggressive forms of prostate cancer, i.e., cases found to be metastatic at time of diagnosis between 1988 and 1994 after a negative digital rectal examination in 1988, we found that obesity at ages 5 and 10 had a strong inverse association (RR = 0.16 with 95% CI = 0.05-0.54, between high and low quintiles at age 10) and that tallness had a strong direct association with risk of metastatic disease (RR = 2.29 with 95% CI = 1.04-5.05, for height > or = 74 inches versus < or = 68 inches). Our findings suggest that the preadult hormonal milieu, as reflected in attained height and childhood obesity, may have a strong influence on prostate carcinogenesis.
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PMID:Height, body weight, and risk of prostate cancer. 926 67

The complex process of carcinogenesis is mainly due to environmental factors and therefore preventable. Diet may account for about 35% of cancer cases; risk factors and protective factors are discussed. Accordingly, obesity is associated with an increased risk of endometrial and postmenopausal breast cancers. Less clear is the relationship with colorectal and prostate cancer. The observed inverse association of body weight with lung cancer risk is most probably confounded by smoking habits and/or the effect of preclinical cancer. The risk factor fat has been studied mainly in relation to colorectal, breast and prostate cancer; the results are controversial. More consistent are the associations between (red) meat consumption and risk of colorectal and prostate cancer. Alcohol is a risk factor for tumors of the upper gastrointestinal tract, the hepatocellular carcinoma and the (distal) colorectal cancer. Even small amounts of alcohol seem to increase the risk of breast cancer. Residues, contaminants, mycotoxins and additives like benzopyrene, nitrosamine(s), and aflatoxine are associated with a smaller risk of cancer than "overnutrition". High intake of fruit and vegetables is related to a reduced risk of lung cancer and cancer of the upper gastrointestinal tract. What the specific chemicals in fruits and vegetables are that are responsible for this association are still unclear. Despite only weak associations between dietary factors and cancer risk, for potential protective effects it is recommendable to increase the consumption of fruit and vegetables, to avoid obesity, to reduce the intake of fat, meat and alcohol and to avoid cured, pickled, smoked, and mouldy food.
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PMID:[The significance of nutrition in primary prevention of cancer]. 938 16

A high correlation between national per capita disappearance of fat and national rates of colon cancer led to the hypothesis that consumption of fat, especially from animal sources, increases risk for colon cancer. Over the past two decades, this hypothesis has been tested in numerous case-control and cohort studies. In general, neither case-control nor cohort studies find that the total fat composition of the diet increases risk of colon cancer. Case-control studies frequently find that total energy consumption is related to a higher risk of colon cancer, but this result is difficult to interpret because physical activity appears to be protective whereas obesity increases risk. In contrast with the results for total fat, epidemiologic data regarding the role of specific fatty acids are sparse. Nonetheless, useful information regarding major fatty acids may be inferred from the numerous studies that have examined major source of various fats in relation to colon cancer. Intake of red meat or beef has been related to colon cancer risk in most case-control and cohort studies, whereas dietary fat from sources other than red meat, including dairy, poultry, and vegetable oils, does not increase risk of colon cancer. The apparent influence of red meat does not appear to be mediated through its total lipid content, suggesting that other factors such as heterocyclic amines formed during cooking may be critical. Mechanisms whereby fat or red meat may influence colon carcinogenesis are discussed, although none appear compelling.
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PMID:The role of fat, fatty acids, and total energy intake in the etiology of human colon cancer. 939 16


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