Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several major epidemiological studies have reported significant mortality rates (SMRs) for both rare cancers (soft tissue sarcoma, non-Hodgkin's, lymphoma, liver) and the more common cancers (lung, colon, etc), all allegedly caused by TCDD. In this paper, we use the potency of TCDD in animals to establish a plausible worst case cancer risk and ask whether its likely that TCDD is responsible for the epidemiological findings assuming the animal carcinogenic potency is applicable to the conditions of human exposure. Two new features of the technique are the use of measured TCDD blood levels in both animals and humans for dose scale-up and the calculation of an integrated life-time exposure for the exposed workers using measured blood levels. On the basis of the stated assumptions it appears unlikely that any of the major epidemiological studies, with the possible exception of the NIOSH study have adequate power to detect the common cancers potentially caused by TCDD.
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PMID:Dioxin--an analysis of the major human studies: comparison with animal-based cancer risks. 760 66

Epidemiological hypotheses on disease etiology, generated by the observation of geographic distribution and time trends, can be confirmed or refuted by analytical investigations on specific risk factors. In the case of leukemias, lymphomas and myelomas, however, hypothesis generation is limited by the use of the ICD classification in mortality and incidence statistics. We compared recent incidence data in different parts of the world and at different times for leukemias, lymphomas and myelomas. The incidence rate of non-Hodgkin's lymphomas (NHL) is increasing in most Western countries, while trends for the other hematolymphopoietic malignancies are strikingly stable. To formulate hypotheses on the causes of this pattern would require a more appropriate classification of descriptive data. Excesses of non-Hodgkin's lymphomas have been observed in populations exposed to phenoxy-acetic acid herbicides, to insecticides and to organic solvents. Some of these exposures, in particular TCDD, which is a contaminant of phenoxy herbicides, DDT and chlorinated solvents, have been reported to alter cell-mediated immunity. The incidence of NHL is also increased among subjects with HIV infection and subjects undergoing heart or kidney transplantation, all of whom experience immunodeficiency. A hypothesis that has been put forward recently is that the NHL increase is related to increased exposure to sunlight, which has immunosuppressive effects. From a mechanistic point of view, one can hypothesize that NHL is caused by exposures that induce proliferation and immortalization of B-cells, followed by T-cell impairment entailing cell-mediated immune deficiency.
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PMID:Incidence and time trends for lymphomas, leukemias and myelomas: hypothesis generation. Working Group on the Epidemiology of Hematolymphopoietic Malignancies in Italy. 864 39

Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental animals, whereas the evidence in humans is limited. We examined cancer mortality from 1976 to 1991 among residents of Seveso, Italy, which was highly contaminated after an industrial accident. The area was divided into zones with decreasing exposure to dioxin (A = highest, B = lower, R = lowest). The population of a surrounding noncontaminated area was used as a reference group. Zone A was small (11,516 person-years); in that zone, we saw a moderate increase in mortality from digestive cancer among women [relative risk (RR) = 1.5; 95% confidence interval (CI) = 0.5-3.5]. In zone B, we also saw excesses at digestive sites (83,610 person-years), 10 years after the accident. Women had an increased mortality from stomach cancer (RR = 2.4; 95% CI = 0.8-5.7), and men had increased mortality from rectal cancer (RR = 6.2; 95% CI = 1.7-15.9). Hematologic neoplasms were increased. The highest risks were seen in zone B for leukemia in men (RR = 3.1; 95% CI = 1.3-6.4), multiple myeloma in women (RR = 6.6; 95% CI = 1.8-16.8), and Hodgkin's disease in both genders (RR = 3.3; 95% CI = 0.4-11.9 in men; and RR = 6.5; 95% CI = 0.7-23.5 in women). Soft tissue sarcoma was elevated only among zone R males (256,408 person-years; RR = 2.1; 95% CI = 0.6-5.4). We found no increase for all-cancer mortality or major specific sites (for example, respiratory among males, breast among females). The specific excesses that we observed were not explained by bias or confounding, and their association with dioxin exposure is plausible. The follow-up is continuing.
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PMID:Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident". 934 64

The epidemiological evidence from the most highly 2,3,7,8-TCDD-exposed cohorts studied produces the strongest evidence of increased risks for all cancer combined, along with less strong evidence of increased risks for cancer of particular sites such as non-Hodgkin lymphoma, soft-tissue sarcoma and lung cancer. The relative risk for all cancer combined in the most highly exposed and longer-latency sub-cohorts is 1.4. While this relative risk is not likely to be explained by confounding, this possibility cannot be excluded. It should be borne in mind that the general population is exposed to 2-3 orders of magnitude lower levels of TCDD than those experienced by the equivalent life-time dose in the industrial populations examined or the population of Seveso.
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PMID:Studies of cancer in humans. 1091 45

Complex technical mixtures of polychlorinated biphenyls (PCBs) cause liver and thyroid neoplasms in rodents, whereas very few data are available on the carcinogenic potency of single non-dioxinlike (NDL) PCB congeners. In most genotoxicity assays technical PCB mixtures and individual congeners were inactive, suggesting that PCBs act as indirect, nongenotoxic carcinogens. Various mechanisms, including suppression of apoptosis in preneoplastic cells or inhibition of intercellular communication, have been suggested to be active in liver tumor promotion by PCBs. A decrease in thyroid hormone levels after PCB treatment has been suggested to play a role in the development of thyroid neoplasms in rats; however, other mechanisms may also be involved. Results from a chronic carcinogenicity study in rats indicate that not the dose of total PCBs but the total TCDD or toxic equivalents (TEQs) associated with "dioxinlike" (DL) constituents within a technical mixture are mainly if not exclusively responsible for the development of liver neoplasms in female rats. Quantitative comparison reveals almost identical dose-response curves for the total TEQs in various technical PCB mixtures and for TCDD as inducers of hepatic neoplasms in female rats. Tumor promotion experiments have shown, however, that, after initiation with a genotoxic carcinogen, technical PCB mixtures and individual DL-and NDL-PCBs act as liver tumor promoters in rodents. Based on these data, a weak carcinogenic potency of individual NDL-PCB congeners cannot be excluded. In epidemiological studies, increased mortality from cancers of the liver, gallbladder, biliary tract, gastrointestinal tract, and from brain cancer and malignant melanoma were observed in workers exposed to a series of technical PCB mixtures. A significant association between PCB concentrations in adipose tissue and non-Hodgkins lymphoma was found in another study. While in all human studies mixed exposure to DL-and NDL-PCBs occurred, no comprehensive data are available on the relative contribution of NDL-PCBs to the overall external and/or internal PCB exposure in those cohorts.
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PMID:Carcinogenicity of "non-dioxinlike" polychlorinated biphenyls. 1705 81

Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8-TCDD) and some other dioxin congeners is long time discussed by epidemiological and experimental studies, often with conflicting findings. The inclusion of 2,3,7,8-TCDD in Group 1 by 1ARC in 1997 was based essentially on mechanistic evidence and experimental studies despite the limited evidence in humans. This procedure generated a lot of controversy. Some scientists agree with this classification and sometimes suggested increased cancer mortality risk with TCDD daily intake similar to those of the general population. Other authors re-analyzing data mainly from caselist previously investigated did not confirm the 2,3,7,8-TCDD carcinogenicity. In the review process of carcinogenic substances by IARC in 2010, the evidence for 2,3,7,8-TCDD carcinogenicity in humans upgraded from limited to sufficient, due to confirmed and integrated epidemiological evidences. It is also confirmed that these findings relate to all cancers combined, while for some "classic" cancers related to TCDD (as soft tissue sarcoma and non-Hodgkin lymphoma) the evidence remains limited. In this paper a literature review accompanied by comments is reported with the aim to provide information about the evaluation process and tools for its more critical and scrupulous interpretation.
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PMID:[Classification as carcinogenic for 2,3,7,8-tetrachlorodibenzo-para-dioxin: an eventful journey]. 2142 34

Dioxin exposure and its effect on hematopoiesis and cancer have been largely investigated in both human and non-human settings. Here we systematically reviewed literature to address the question of what we know about TCDD biology and exposure. Most effects are due to TCDD interaction with a receptor of xenobiotics called AHR, which is ubiquitously represented and also works on hematopoietic myeloid and lymphoid stem cells, inducing proliferation and stem cell release from bone marrow to peripheral circulation. Epidemiologic studies on TCDD exposure demonstrated an association with onco-hematologic diseases, particularly with non Hodgkin lymphomas and multiple myeloma, and non hematologic cancers, such as sarcomas, although these relationships are affected by multiple confounding factors.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) role in hematopoiesis and in hematologic diseases: A critical review. 2776 85