Re: "Use of electric blankets and risk of postmenopausal breast cancer".
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Biomedical subjects
Publications and source records attributed to R G Stevens.
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Breast cancer is the leading cause of cancer death in women in the industrialized world, and the rates of breast cancer incidence are rising. Although risk is high in industrialized societies, it is low in nonindustrialized areas. The search for the causes of breast cancer has not yet yielded a convincing explanation for the geographic and temporal patterns in the occurrence of breast cancer. Generation of electric power is a hallmark of industrialization, and two products of electric power, light-at-night (LAN) and electromagnetic fields (EMF), may affect breast cancer risk. Exposure to either LAN or EMF can decrease production of melatonin by the pineal gland. Melatonin, in turn, has been shown to suppress mammary tumorigenesis in experimental animals. Moreover, recent epidemiological findings indicate an increased risk of breast cancer in workers occupationally exposed to EMF. On the basis of these considerations, it is proposed that the use of electrical power accounts, in part, for the higher risks of breast cancer in industrialized societies.
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Stationary-phase Chinese hamster ovary cells were cultured in medium containing ferritin (approximately 19% iron by weight) added at concentrations ranging from 0 to 128 micrograms/ml. One set of cultures was unirradiated, and another set was exposed to 4.0 Gy of X-ray. Clonogenic cell survival was assessed in each set of cultures. In the absence of added ferritin, 4.0 Gy killed approximately 50% of the cells. In the absence of radiation, ferritin was not toxic at less than 48 micrograms/ml; above 48 micrograms/ml, toxicity increased with concentration. Apoferritin was not toxic at any concentration tested (up to 1000 micrograms/ml). Although 32 micrograms/ml ferritin, reflecting only a 3-6 fold increase in iron concentration over normal serum, was not toxic, it reduced the survival of X-irradiated cells by an additional 75%. These results indicate that a sublethal concentration of ferritin can be a potent radiosensitizer. This suggests the possibility that high body iron stores may increase susceptibility to radiation injury in humans.
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Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.
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Four epidemiological studies have been performed that are generally consistent with the hypothesis that increased available body iron stores increase the risk of cancer or of general mortality. In a study based on the First National Health and Nutrition Examination Survey in the United States (NHANES), 232 men who developed cancer over a ten year period had a mean transferrin saturation of 33.1% at least 4 years before diagnosis, whereas 3,113 men who did not develop cancer had a transferrin saturation of 30.7% (p = 0.002). The hypothesis is based on two possible biological mechanisms. First, iron can catalyse the production of oxygen radicals and these may be proximate carcinogens. Second, iron may be a limiting nutrient to the growth and replication of a cancer cell. There are at least five areas of potential research related to iron and cancer based on these biological mechanisms: (1) etiology of cancer, (2) etiology of radiation-induced cancer, (3) prognosis after cancer diagnosis, (4) cancer risk resulting from therapy, and (5) interactions with other biochemical factors. An unexpected finding of the human studies done to date has been a highly significant negative association of serum albumin and long term cancer risk. Serum albumin is lower in smokers and older people, however, the negative association persists after controlling for these factors.
Associations of smoking habit with serum levels of total protein as well as protein fractions were studied in a population consisting of 4,739 atomic-bomb survivors and unexposed control subjects in Hiroshima, Japan who participated in the 1979-1981 period of the Adult Health Study, an ongoing health follow-up program of the Radiation Effects Research Foundation. Smoking was strongly related to serum protein concentration after correction for age, sex, and body mass index. Among current smokers, levels of total protein, beta globulin, and gamma globulin were significantly lower and levels of alpha-1 and alpha-2 globulin were significantly higher, when compared with nonsmokers. For serum albumin levels a decrease was also noted, but it failed to attain statistical significance. Ex-smokers were indistinguishable from nonsmokers in terms of the serum protein levels analyzed. With an increase of the amount of daily cigarette consumption, monotonic increases of serum levels were observed only in alpha-1 globulin. Duration of smoking was related to increased alpha-1 and alpha-2 globulin. Smoking duration was also associated with albumin level, but the trend was not monotonic. The radiation exposure effect on serum protein level was significant in several instances but was in general much smaller than the smoking effect, and its inclusion in the regression models did not noticeably affect the association between smoking and serum proteins.
Results of several epidemiological studies of workers exposed occupationally to low levels of radiation have been reported but have not included data on smoking. The authors conducted a case-cohort study of male workers at the Hanford Site with an objective of investigating the association between lung-cancer risk and occupational radiation exposure with appropriate adjustment for tobacco use. Eighty-six lung-cancer deaths for the period 1965-1980 and a stratified random sample of 445 subcohort members were included in the study. Tobacco-use data were obtained from medical records collected over each subject's period of employment. Data from this study were analyzed using methods that took into account both the case-cohort design and changes over time in the quality of the tobacco-use data collected. Tobacco use was not strongly related to the level of radiation exposure, and adjustment for tobacco use did not greatly modify results of analyses assessing the association between lung-cancer risk and cumulative dose equivalent. With or without adjustment for tobacco use, the estimated risks per unit of cumulative dose equivalent were negative, but the 95% confidence intervals were wide and included values several times those estimated from populations with high levels of irradiation.
Increased iron content of cells and tissue may increase the risk of cancer. In particular, high available iron status may increase the risk of a radiation-induced cancer. There are two possible mechanisms for this effect: iron can catalyze the production of oxygen radicals, and it may be a limiting nutrient to the growth and development of a transformed cell in vivo. Given the high available iron content of the western diet and the fact that the world is changing to the western model, it is important to determine if high iron increases the risk of cancer.
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Reports from recent epidemiological studies have suggested a possible association between extremely low frequency (ELF; including 50- or 60-Hz) electric- and magnetic-field exposure, and increased risk of certain cancers, depression, and miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological factor in these effects. Work in our laboratory and elsewhere has shown that ELF electromagnetic-field exposure can alter the normal circadian rhythm of melatonin synthesis and release in the pineal gland. Consequences of reduced or inappropriately timed melatonin release on the endocrine, neuronal, and immune systems are discussed. Laboratory data linking ELF field exposure to changes in pineal circadian rhythms in both animals and humans are reviewed. The authors suggest that the pineal gland, in addition to being a convenient locus for measuring dyschronogenic effects of ELF field exposure, may play a central role in biological response to these fields via alterations in the melatonin signal.
Rats injected peripherally with 5-hydroxytryptamine (5-HT) showed a dose-dependent decrease in food intake following overnight fasting. The peripheral 5-HT-2 antagonist xylamidine had no effect on food intake when administered alone, but antagonised 5-HT-induced anorexia. However, at the highest dose of 5-HT (5 mg/kg), both doses of xylamidine (1.0 and 2.0 mg/kg) displayed the same degree of antagonism to the anorectic effect, but failed to block it completely. The results are discussed in terms of 5-HT receptor subtypes, and it is suggested that non-5-HT-2 receptors may be partially responsible for the mediation of peripheral 5-HT-induced anorexia.
The relationship between prior allergies and adult acute myelocytic leukemia was investigated in a population-based case-control study. Based on data from personal interviews of 98 cases and 133 controls, a history of any type of allergy was associated with a significantly decreased risk of acute myelocytic leukemia (OR = 0.35, 95% CI = 0.20-0.60). Risk declined with the total number of specific allergies reported (p less than 0.001), and was reduced in relation to a history of prior asthma, eczema and hives. The implications of these findings in relation to natural immune surveillance against developing neoplasms are discussed.
Small but significant variations in clinical biochemical indices may be of great biological significance. Earlier studies conducted on small, chronically ill, hospitalized, anemic, and/or malnourished population samples suggested associations between body size and composition and indices of iron metabolism, serum protein, and plasma cholesterol. We studied a large, nonhospitalized probability sample of women and men in the First US Health and Nutrition Examination Survey (NHANES I) to characterize these associations. Greater weight, stature, body mass index (BMI), skinfold thickness, and lean body mass (LBM) are associated with higher hemoglobin, hematocrit, and total iron-binding capacity. LBM and body fat are weakly related to serum albumin concentrations in men and to serum total protein concentrations in women. Total cholesterol concentrations are directly associated with weight, body fat, and LBM and are more strongly associated with central than peripheral obesity. Constitutional factors may be important for clinical assessment and for interpretation of epidemiologic studies.
Because of evidence that increased body iron stores are associated with an increased risk of cancer, we examined iron status and cancer risk in the first National Health and Nutrition Examination Survey, a survey of more than 14,000 adults begun in 1971, with follow-up between 1981 and 1984. Among 242 men in whom cancer developed, the mean total iron-binding capacity was significantly lower (61.4 vs. 62.9 mumol per liter; P = 0.01) and transferrin saturation was significantly higher (33.1 vs. 30.7 percent; P = 0.002) than among 3113 men who remained free of cancer. The risk of cancer in men in each quartile of transferrin-saturation level relative to the lowest quartile was 1.00, 1.01, 1.10, and 1.37 (P = 0.02 for trend). The serum albumin level was significantly lower in men in whom cancer developed than in those who remained cancer-free. Among women, those in whom cancer developed did not have significantly lower total iron-binding capacity or higher transferrin saturation than those who remained cancer-free. However, a post hoc examination of 5367 women (203 with cancer) yielded a relative risk of 1.3 (95 percent confidence interval, 0.9 to 1.9) associated with a very high transferrin saturation (greater than or equal to 36.8 percent, a value in the highest quartile among men); in 5228 women with at least six years of follow-up (149 with cancer), the relative risk associated with transferrin saturation above this level was 1.5 (1.0 to 2.2). These results are consistent with the hypothesis that high body iron stores increase the risk of cancer in men. The possibility that a similar association exists in women requires further study.
The potential of thermography as a screening technique for the early detection of breast cancer was assessed by using difference of Gaussian filtering to isolate and quantify the vascular contents of breast thermograms. Forty-five patients found to have breast cancer and 49 patients who developed breast cancer within 5 years of being screened were paired with normal variants and the thermograms of each group were assessed. No statistically significant separation was resolved between either of the two paired groups implying that the vascular content of isolated thermograms is unable to provide meaningful indications of breast cancer. The processing algorithm, although developed initially for thermograms, is equally valid for other diagnostic imaging techniques and could be of use where it is required to isolate vascularity or other fine detail from larger body structures.