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

Thyroid cancer is a relatively rare cancer (5 new cases/y/10(5) inhabitants). An excess of thyroid carcinoma has been found in some but not in all goiter endemic areas. Follicular and anaplastic carcinomas have been found particularly frequent in regions of goitre endemia. A significant increase of thyroid carcinoma has also been found in iodine sufficient areas (Norway, Iceland, Hawaii). In several surveys a positive correlation has been found between parity and incidence of differentiated thyroid carcinoma. Natural goitrogens and chemotherapeutic agents have been proved to induce hyperplasia but their role in carcinogenesis of exposed populations is not yet definitely ascertained. Exposure to external radiation is carcinogenic for the thyroid both in human and in experimental animals. Patients treated for hyperthyroidism or thyroid cancer or given diagnostic doses of 131-I (0.5 Gy/test) indicate that under these conditions 131-I is not carcinogenic. Findings on population exposed to radioactive fallout showed an increased incidence of thyroid carcinomas compared to unexposed populations. After the Chernobyl accident (1986) particular attention was given to calculate the risk of thyroid cancer caused by the fallout of 131-I. Up to now a considerable increase of thyroid carcinoma has been reported in children of a region near Chernobyl (Belarus).
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PMID:Aetiology of thyroid cancer: an epidemiological overview. 753 43

A total of 154 cases of thyroid cancer in children under 15 were registered in England and Wales over a period of 30 years, an incidence of about 0.5 per million per year. A total of 4.5 cases per year were registered in 1963-72, 4.9 in 1973-82 and 5.8 in 1983-92. A rapid rise in incidence with age occurred after the age of 5. Malignancy was confirmed in 92% of the cases in which tissue was available. Of these, 68% were papillary carcinomas, 11% follicular carcinomas and 17% medullary carcinomas. There were two spindle cell tumours with mucous cysts and one teratoma. The increased frequency but small size of medullary carcinomas in the second half of the period suggested that this increase was due to the introduction of screening; it accounted for most of the rise in crude incidence rats with time. The sex ratio (F:M) in all registered cases in the differentiated follicular cell carcinoma groups in children aged under 10 was 1.2:1, and 3.6:1 in the older children. Five children with differentiated thyroid cancer of follicular cell origin died up to 17 years after diagnosis. Two of the eight children aged 9 or less with a 20 year follow-up died, compared with three of 28 older children. An unusual group of differentiated carcinomas showed solid or follicular architecture. These tumours were unencapsulated, often widely invasive, contained psammoma bodies but little or no papillary architecture and the nuclei often lacked prominent grooving. This childhood type of papillary carcinoma contrasted with the classical type commonly found in the adult, which was present in one of 13 confirmed papillary carcinomas in children aged less than 10, compared with 20 of 35 older children. These observations show that thyroid carcinoma in very young children has a different spectrum of histological types from both older children and adults. From the age of about 10 well-differentiated papillary carcinomas rapidly increase in frequency in females, so that the other types come to form only a small proportion of the total. These differences, and the lower incidence but poorer prognosis of thyroid carcinoma in men and the poorer prognosis in post- as compared with premenopausal women, are compatible with a major role for sex hormones in thyroid carcinogenesis in females during the reproductive period. This study documents the incidence of childhood thyroid cancer in England and Wales, explains the rise in crude incidence rates, shows differences between carcinomas in children under and over the age of ten which may correlate with puberty, and draws attention to an unusual aggressive type of childhood papillary carcinoma. It illustrates the value to crude registry data of a pathology review.
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PMID:Childhood thyroid cancer in England and Wales. 766 94

The association between genetic disorders and diverse cancers has provided clues for laboratory research into carcinogenesis. Such an opportunity now arises from studies of cancer in Werner syndrome (WRN). Soft-tissue sarcoma (STS) and benign meningioma have been associated with WRN, an autosomal recessive disorder characterized by premature aging, more commonly reported in Japan than elsewhere, in part because of inbreeding. In the literature we found 124 case-reports of neoplasia and WRN from Japan and 34 from outside Japan, 1939-August, 1995. They reveal a greater diversity of neoplasia in WRN than was previously known. In Japanese, there were 127 cancers, 14 benign meningioma, and 5 myeloid disorders, as compared with 30, 7 and 2 respectively in non-Japanese. The ratio of epithelial to non-epithelial cancers was about 1:1 for Japanese and for non-Japanese instead of the usual 10:1. Both series had excess of STS, osteosarcoma, myeloid disorders, and benign meningioma. In addition, the Japanese had an excess of thyroid cancer (20 versus 2 cases in non-Japanese) and melanoma (21 versus 3 cases), including 5 intranasal and 13 of the feet. STS, osteosarcoma, melanoma, and thyroid carcinoma accounted for 57% of all cancer in WRN as compared with 2% expected based on the Osaka population at 25-64 years of age. Multiple tumors were reported in 19 Japanese and 5 non-Japanese. In Japan, nine first-degree relatives had WRN and cancer, six of whom were concordant as to site and/or cell type. The WRN gene has been mapped to chromosome 8p. The high frequency of thyroid cancer and melanoma in Japanese, not found in Caucasians, may be related to a report of linkage disequilibrium with the WRN gene in Japanese but not in Caucasians and to haplotype differences within and between the two races, suggesting multiple independent mutations.
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PMID:Excess of rare cancers in Werner syndrome (adult progeria). 872 14

Surgically resected thyroids from 425 patients with thyroid disease other than carcinoma of follicular cell derivation were thoroughly examined for occult micropapillary carcinoma (MPC). There were 317 cases of nodular hyperplasia, 36 of thyroiditis, 44 follicular adenomas, and 28 others. Glands were sectioned at 2- to 3-mm intervals and fixed in formalin. Every section was examined histologically. There were 71 cases (16.7%) of MPC containing 118 tumors. Among 343 women, 51 (14.9%) had MPC; among 82 men, 20 (24.4%) had MPC. The average age of all of the patients was 46.9 years and of those with MPC, 50.5 years. The occurrence of MPC peaked between 40 and 70 years and declined in older patients. MPC was found in 8.9% of patients who underwent lobectomies, 10.8% who had hemithyroidectomies, and 24.1% of those who had total thyroidectomies. Logistic regression analysis revealed significant associations between the presence of MPC and the patient sex, age, and extent of surgery; in contrast, there was no association between the occurrence of MPC and the underlying thyroid disease. These data indicate that MPC is present in up to 24.1% of thyroids removed for unrelated thyroid disease. The predominance of this lesion in men is in striking contrast to the occurrence of clinically significant thyroid cancer. This suggests that the initiation of carcinogenesis is not sexually dimorphic, whereas promoters of tumor growth are. A rational management of this common disease awaits the results of careful controlled trials.
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PMID:Occult micropapillary carcinoma associated with benign follicular thyroid disease and unrelated thyroid neoplasms. 887 22

In a population-based case-control study in the Uppsala-Orebro Health Care Region of Sweden, the histories of cancer among parents of 517 histologically confirmed cases of papillary and follicular carcinoma and of a similar number of sex- and age-matched controls were compared. The parental history of cancer was compiled through information from death certificates and from the nationwide Cancer Register. The incidence of malignancies in a cohort of parents of cases of thyroid cancer was also compared with the incidence in the whole Swedish population. A maternal history of cancer was more common among women with follicular carcinoma than among their controls (OR 2.11, 95% CI 0.96-4.67). Parents of probands with papillary carcinoma had an increased risk of thyroid cancer (OR 4.25, 95% CI 1.16-10.89), and mothers of probands with follicular carcinoma had an increased risk of stomach cancer (OR 3.65, 95% CI 0.99-9.35) compared with the general population. Cancer of the lung, breast, and pancreas were less common than in the general population. Familial cases of thyroid cancer were not limited to the papillary type. An inheritable pattern of carcinogenesis is possible for certain differentiated non-medullary thyroid cancers, but shared environmental exposures may also explain the parent-child associations of cancer in this study.
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PMID:Parental cancer and risk of papillary and follicular thyroid carcinoma. 902 Apr 97

Cytogenetic and molecular analyses of thyroid tumors have indicated that these neoplasms represent a good model for analyzing human epithelial cell multistep carcinogenesis. They comprise, in fact, a broad spectrum of lesions with different phenotypes and variable biological and clinical behavior. Molecular analysis has detected specific genetic alterations in the different types of thyroid tumors. In particular, the well-differentiated carcinomas of the papillary type are characterized by activation of the receptor tyrosine kinases (RTKs), RET and NTRK1 proto-oncogenes. Cytogenetic analysis of these tumors has contributed to defining the chromosomal mechanisms leading to RTK oncogenic activation. In the majority of cases, intrachromosomal inversions of chromosome 10 and chromosome 1 led to the formation of RET-derived and NTRK1-derived oncogenes, respectively. Interestingly, molecular analysis of these oncogenes revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the oncogenic rearrangements led to the identification of a breakpoint cluster region in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with papillary carcinomas and RET activation has been suggested to be related to this event. Conversely, RAS point mutations are frequently observed in tumors with follicular histology and have been associated with metastatic dissemination. Iodide-deficient areas seem to provide a higher frequency of RAS positive follicular carcinomas. Finally, a high prevalence of TPS3 point mutations has been detected only in undifferentiated or anaplastic carcinomas and found to correlate inversely with 8CL2 expression. All of these findings are contributing to the definition of genetic and environmental factors relevant for the pathogenesis of thyroid tumors. Moreover, the characterization of specific genetic lesions could provide significant molecular tools for a better differential diagnosis and for the development of novel therapeutic avenues for thyroid cancer.
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PMID:Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial follicular cells. 916 91

Thyroid glands from 162 patients were examined for occult thyroid pathology at autopsy. The patients were residents of Kiev, aged 16 to 82 years, without known thyroid disease. Abnormalities were observed in 66 of the 162 cases (40.7%) and included nodular hyperplasia (13.6%), follicular adenoma (4.9%), and thyroiditis (9.5%). Thyroid carcinoma was found in 11.7% of cases (18 papillary microcarcinomas and one follicular oncocytic carcinoma). No cancer was found in the thyroids of patients under 35 years of age. Cancer was predominant in women, but there were no significant differences in the frequency of occult carcinoma with increased age. The neoplasms varied in size from microscopic foci to 9 mm in diameter; most (63%) were over 5 mm. The cancer incidence rate in our study was lower than that found in Finland and Japan, but higher than in most other published series. The absence of a correlation between the rather high frequency of latent thyroid cancer in autopsy data and the relatively low annual incidence of clinically evident thyroid cancer in Ukraine residents may reflect the impact of initiating factors on carcinogenesis of the thyroid. Our results suggest that environmental factors in the area of Ukraine, contaminated by the Chernobyl accident, may play an important role in the etiology of thyroid cancer, but further research is needed.
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PMID:Latent thyroid pathology in residents of Kiev, Ukraine. 921 14

Ionizing radiation is a well-known risk factor of cancer development, but the mechanism of radiation induced carcinogenesis is not clear. Chromosomal rearrangements induced by radiation most likely are one of the principal genetic alterations resulting in malignant transformation. The chimeric BCR-ABL associated with chronic myelogenous leukemia (CML) and H4-RET oncogenes associated with thyroid papillary carcinoma are the result of a translocation and inversion, respectively. In vitro studies showed these genes were induced by high-doses of X-irradiation in cell lines. Studies also show that therapeutic external X-ray doses as high as 60 Gy for treatment of various childhood cancers including Hodgkin's disease significantly increase the risk of thyroid cancer. Therefore, we examined the induction and persistence of these chimeric genes in human thyroid tissues transplanted in scid mice after 50 Gy exposure as a function of time for 2 months to elucidate the early events of thyroid carcinogenesis. The H4-RET genes were detected on day 2 and throughout the 2 month period. On the other hand, BCR-ABL genes were detected on day 2 and were undetectable subsequently. These results suggest that ionizing radiation causes various oncogene activations, but cells with only specific gene alteration uniquely associated with thyroid carcinogenesis are selectively retained demonstrating one of the early events in the beginnings of radiation carcinogenesis in human thyroid tissues.
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PMID:Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogenesis. 933 21

Over 500 cases of thyroid cancer were diagnosed in Belarus between 1986 and 1995 among persons exposed as children (under 15 years of age) to radioactive contamination from the Chernobyl nuclear accident. There is little doubt that radioactive iodine isotopes emitted during the nuclear explosion and subsequent fire were instrumental in causing malignancy in this particular organ. Comparison of the observed geographic distribution of Chernobyl-associated thyroid cancer incidence rates by districts with contamination maps of radioactive fallout shows a better fit for estimated 131I contamination than for 137Cs. Because 131I used for medical purposes had not been considered carcinogenic in humans in the past, and in view of the unusually short latency period between exposure and clinical manifestation of cancer, it is suspected that not only 131I but also energy-rich shorter-lived radioiodines may have played a role in post-Chernobyl thyroid carcinogenesis. Measurements of iodine isotopes are not available, but reconstruction of geographic distributions and estimations of radioactive fallout based on meteorological observations immediately following the accident could provide a basis for comparison with the distribution of thyroid cancer cases. In this paper, data from the Epidemiological Cancer Register for Belarus will be used to show geographic and time trends of thyroid cancer incidence rates in the period from 1986 to 1995 among persons who were exposed as children, and these will be compared with the estimated contamination by radioiodines. Tentative conclusions are drawn from the available evidence and further research requirements discussed.
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PMID:Chernobyl-related thyroid cancer: what evidence for role of short-lived iodines? 946 68

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.
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PMID:Occupational and environmental radiation and cancer. 949 95


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