Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although radioiodine is increasingly the treatment of choice in hyperthyroidism, there are regional differences in its use which reflect, in part, concerns regarding safety. We investigated attitudes amongst general practitioners and consultant physicians to the role of radioiodine therapy, and reviewed our own radioiodine prescribing in patients aged less than 40 to elucidate any influence of age and/or sex. We surveyed general practitioners in the former Central Birmingham Health District and consultant physicians in the West Midlands Region to investigate treatment preferences in hyperthyroidism and perceived risk from radioiodine of hypothyroidism, carcinogenesis and infertility. Of 230 general practitioner and 130 consultant physician respondents, less than 1% considered radioiodine the treatment of choice in a 25-year-old female presenting with hyperthyroidism. At relapse after antithyroid drug treatment in a 25-year-old female, only 16.5% of general practitioners and 23.9% of physicians advocated radioiodine, the greatest number preferring partial thyroidectomy. For a 65-year-old at presentation, 49.1% of general practitioners and 62.3% of physicians considered radioiodine the treatment of choice. More than 10% failed to note the risk of hypothyroidism following radioiodine, while 11-34% perceived increased risk of malignancy or infertility. Review of our own practice demonstrated that of 100 patients given radioiodine, 94% were cured of hyperthyroidism when reviewed at a mean of 2.4 years from latest treatment, 70% being hypothyroid. Females given radioiodine were treated less promptly following diagnosis of hyperthyroidism than males (2.2 +/- 0.26 years vs. 1.6 +/- 0.4) and were more likely to have received a preceding course of antithyroid drugs (78% vs. 57%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Radioiodine therapy for hyperthyroidism in young patients--perception of risk and use. 821 Mar 7

Recently, much attention in both the medical and lay communities has been focused on a possible association between fertility drug use and invasive ovarian cancer, and ovarian tumors of low malignant potential. A causal relationship, if shown to exist, has important implications. In the past year, several large case-control and cohort studies have attempted to address this issue. However, interpretation of the available data has been hampered by a number of factors. Retrospective study designs, small numbers of ovarian cancer cases, and inconsistent reporting of fertility drug use and type of infertility have all been common methodological shortcomings. The known ovarian cancer risk factors of low parity and infertility have been particularly difficult to separate from any effect of ovulation induction. The current epidemiologic data are insufficient to implicate conclusively specific fertility medications in ovarian carcinogenesis. The data do suggest that women with refractory infertility may constitute a high-risk population for developing ovarian cancer, independent of fertility drug use. Until the relationship between ovulation induction and ovarian cancer risk is defined more accurately, a high index of clinical suspicion for ovarian neoplasms is indicated before, during, and after treating women for infertility.
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PMID:The risk of ovarian cancer after treatment for infertility. 877 56

Dibromochloropropane, DBCP, has had a seminal role in our current understanding of how to prevent chemical risks to health. Early toxicological studies showed its special impact on the testes, and detection of its mutagenic potency was soon followed by demonstration of its carcinogenicity to animals. Its commercial use as a useful nematocide ignored, at first, these warnings from the laboratory. When production workers, first in California and then in Israel, found they were sterile as a result of their exposure, this was convincing evidence that prevention had failed. The evidence, azospermia, oligospermia, and gonadotrophin response to testicular damage, were found first in production workers. In agricultural applicators in California who used the material, decreased sperm count and increased gonadotrophin levels were found. While production in California, Texas, and Israel was halted, studies continued and so, it seems, did use. Our first Israeli study was of workers on banana crops, and we found convincing evidence of increased spontaneous abortion in their family histories. Follow-up studies among production workers in Israel showed that some recovered testicular function, but among their offspring, otherwise in good health, there was a predominance of females. Those who did not recover from azospermia were those with high levels of follicle stimulating hormone. However data for production workers did not show increased spontaneous abortion. Nor have any studies so far shown increased birth defects or increased infant mortality. Unfavorable reproductive outcomes can be due to other agents, as shown by sprayers in Dutch orchards having hypofecundity (increased interpregnancy period) and sex ratio changes; but the agents responsible have not yet been identified. These experiences have lead to the general acceptance of some implications: (1) Paternal exposures can lead to a variety of unfavorable effects on reproductive outcome, including infertility, spontaneous abortion, and altered sex ratio. (2) Patterns of effects of potent agents in production workers and in applicators or users of chemicals may differ. (3) Although human carcinogenesis has not yet been confirmed, unfavorable reproductive outcomes are a reasonable early indicator of such risk. (4) Shifts in sex ratios of populations may be a subtle sign of more serious risks. (5) Continued use of an agent such as this under circumstances in which these UROs cannot be prevented is unconscionable.
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PMID:Dibromochloropropane: epidemiological findings and current questions. 947 48

Epithelial ovarian cancer is fairly common with high rates in Scandinavia, intermediate rates in western Europe and North America and low rates in the developing countries and in Japan. The 5-year survival rate is less than 40%. Increasing parity consistently gives a strong protection against epithelial ovarian cancer. A lesser degree of protection is probably derived from incomplete pregnancies and lactation. Ages at menarche and menopause are most probably weak predictors of epithelial ovarian cancer risk. Ever users of oral contraceptives (OC) have 30% lower risk compared to never users. The protection increases with duration of OC use, being about 50% after 5 years. The reduced risk among past OC users persists for at least 10 years after cessation of use. Results concerning hormone replacement therapy (HRT) and epithelial ovarian cancer risk are conflicting, but most data point to a weak or no association, but as an increasing number of women use HRT it still seems important to resolve any potential effect. Infertility adds to epithelial ovarian cancer risk in nulliparous women, while temporary fertility problems in parous women do not appear to increase risk. A possible independent risk effect of fertility drug use has not been easy to assess and remains unresolved. It has been particularly difficult to separate the effects of fertility drugs from those of infertility. Tubal ligation and hysterectomy convey protection against epithelial ovarian cancer, possibly through a suppressed ovarian hormone production. The causes of epithelial ovarian cancer are poorly understood, but reproductive hormones are thought to be involved in the aetiology. For a long time the 'incessant' and 'gonadotrophin' hypotheses have been promoted in relation to carcinogenesis. Both hypotheses find support in ovarian cancer epidemiology, and recent progress in molecular biology adds to the understanding of possible aetiological mechanisms. Another hypothesis focuses on the retrograde transport of contaminants or carcinogens through the Fallopian tubes. It is important to establish if the same risk factors apply to the various histological types of ovarian cancer, as particularly the mucinous ovarian tumours seem to present with different risk factors. Another question to resolve is if sporadic vs. inherited cases carry distinct risk profiles. As the hypotheses above do not explain all of the results derived from ovarian cancer epidemiology, there is a need to test additional hypotheses to possibly define preventive programmes and to come closer to the cause of ovarian cancer.
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PMID:Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence. 1020 55

An epidemiological correlation between infertility therapy and ovarian cancer development has been reported in 1992; consequently, the possible role of gonadotropins in ovarian carcinogenesis has received much attention. Here, we review the effect of gonadotropins on epithelial ovarian carcinoma and ovarian surface epithelium (OSE), which is the histogenetic origin of carcinomas. Recent studies have demonstrated that gonadotropin receptors are expressed in OSE and in approximately half of the ovarian carcinomas. Gonadotropins have also been reported to stimulate cell proliferation and to inhibit apoptosis in OSE and ovarian cancer cells. These data suggest that gonadotropins play an important role in the development, progression, and/or chemoresistance of ovarian carcinomas. Hormonal therapy against gonadotropins may be applicable for patients with ovarian carcinoma.
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PMID:Review: gonadotropins and development of ovarian cancer. 1054 2

Despite recent advances in diagnosis and treatment of testicular cancer, its causes remain unknown. The most common conditions known to be associated with testicular cancer are cryptorchidism, infertility, and overexposure to pesticides or radiation. Recent studies also indicate hormones may play a crucial role in testicular tumorigenesis. Our studies show that about half of the male transgenic mice overexpressing aromatase in testis were infertile and/or had larger than normal testicles. Gross pathology and histological analysis showed the mice to have Leydig cell tumors, unilaterally or bilaterally. Serum estradiol levels for transgenic mice were at least twice as high as those for nontransgenic mice. Expression of aromatase and estrogen receptor were also very high in testicular tissue of transgenic mice compared to nontransgenic mice. Consistent with increased estrogenic activity in the testicular tissue, we also saw an increase in the levels of genes involved in cell cycle that are regulated by the estrogen. To obtain a better understanding of the biological significance of testicular tumorigenesis, a reliable animal model is necessary to clarify the mechanisms and correlations associated with human cancers. Here we describe such a model, which shows that overexpression of aromatase results in increased estrogen production and a changed hormone milieu, leading to the induction of testicular cancer (Leydig cell tumors). This predictable and useful model is a potential tool for the study of testicular tumorigenesis, hormonal carcinogenesis, synergistic action of other carcinogens on hormone-induced tumors, and tumor dependency on endocrine factors.
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PMID:Overexpression of aromatase leads to development of testicular leydig cell tumors : an in vivo model for hormone-mediated TesticularCancer. 1062 84

Ovarian cancer varies widely in frequency among different geographic regions and ethnic groups, with a high incidence in Northern Europe and the United States, and a low incidence in Japan. The majority of cases are sporadic, and only 5% to 10% of ovarian cancers are familial. The etiology of ovarian cancer is poorly understood. Models of ovarian carcinogenesis include the theory of incessant ovulation, in which a person's age at ovulation, i.e., lifetime number of ovulatory cycles, is an index of her ovarian cancer risk. Excessive gonadotropin and androgen stimulation of the ovary have been postulated as contributing factors. Exposure of the ovaries to pelvic contaminants and carcinogens may play a role in the pathogenesis of ovarian cancer. Epidemiologic and molecular-genetic studies identify numerous risk and protective factors. The most significant risk factor is a family history of the disease. Recent advances in molecular genetics have found mutations in the BRCA1 and BRCA2 tumor suppressor genes responsible for the majority of hereditary ovarian cancer. Additional risk factors include nulliparity and refractory infertility. Protective factors include multiparity, oral contraceptives, and tubal ligation or hysterectomy. With five years of oral contraceptive use, women can cut their risk of ovarian cancer approximately in half; this also holds true for individuals with a family history. Stage at diagnosis, maximum residual disease following cytoreductive surgery, and performance status are the three major prognostic factors. Using a multimodality approach to treatment, including aggressive cytoreductive surgery and combination chemotherapy, five-year survival rates are as follows: Stage I (93%), Stage II (70%), Stage III (37%), and Stage IV (25%).
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PMID:Ovarian cancer: epidemiology, biology, and prognostic factors. 1088 18

The long-term outcomes of children exposed to antineoplastic agents in utero are not well-defined. Existing data are significantly limited by small numbers, heterogeneous patient populations and regimens, brief and unsystematic assessments in follow-up, and substantial publication bias. Larger, prospective analyses are necessary to draw definitive conclusions. Potential long-term effects include transplacental carcinogenesis, gonadal dysfunction and infertility, compromised physical and neurologic growth and development, transplacental mutagenesis of germ-line tissue, and teratogenicity and carcinogenesis in subsequent generations. Ideally, chemotherapy should be delayed until the fetus is as fully developed as possible. If maternal outcome would be significantly compromised with deferral until delivery, choice and timing of agents should be based on current knowledge of the most effective, least teratogenic drugs. Knowledge of agent-specific toxicities and their potential for late manifestation in the progeny may be prudent in the vigilant long-term follow-up of children exposed to antineoplastic agents in utero.
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PMID:Long-term outcomes of children exposed to antineoplastic agents in utero. 1113 Apr 79

Many factors that can modulate the risk of developing uterine leiomyoma have been identified, including parity. Epidemiological data on decreased risk of developing this disease has been subject to different interpretations regarding whether pregnancy per se is protective or, as leiomyomas are a major cause of infertility, women that develop these tumors are less fertile and thus have lower pregnancy rates. We have utilized an animal model genetically predisposed to uterine leiomyoma to investigate the potential protective effect of pregnancy on the risk of developing this disease. Female Eker rats that carry a mutation in the tuberous sclerosis 2 (Tsc-2) tumor suppressor gene develop uterine leiomyoma with a frequency of 65% when nulliparous. These animals were bred with intact or vasectomized males and tumor incidence determined after a single pregnancy (to confirm fertility) or multiple pregnancies over the lifetime of the animals. Females with multiple litters displayed a dramatic shift in tumor incidence and presentation. Tumor incidence decreased from 71% in single litter females to 10% in females that had multiple litters (average: five litters/animal). Interestingly, females bred with vasectomized males also exhibited a reduced tumor incidence of 41%, suggesting that the hormonal changes associated with early stages of pregnancy that occur in pseudopregnant females may have contributed to the protective effect of pregnancy.
Carcinogenesis 2001 Dec
PMID:Protective effect of pregnancy for development of uterine leiomyoma. 1175 38

Cancer treatments are well known to adversely affect male fertility. Reduction of sperm output arises from the cytotoxic effects of chemo- or radiotherapy upon the spermatogenic epithelium. However, if the epithelium survives there is a hazard to reproduction as the treatments are also mutagenic. The presence of DNA damage in the male genome is shown in animal experiments where there is transgenerational expression as a variety of effects ranging from miscarriage to carcinogenesis. The application of DNA damage methodology to sperm provides the opportunity for direct assessment. The Comet and Chromatin structure assays (SCSA) measure DNA damage by different principles, however, conclusions arising from the data are similar. DNA damage is present in sperm from fertile and infertile men and there is some association with infertility. Both assays detect sperm DNA damage after in vivo treatment with genotoxic agents. In a man treated with chemotherapy for cancer there was increased and persistent DNA damage in sperm. This information is consistent with the generation of human genetic diseases after conception with sperm carrying high loads of DNA damage. Whilst studies have not supported any association between paternal cytotoxic cancer therapy and genetic disease in their children, it would be unwise to discount these observations. The institution of better surveillance of genetic disease in the offspring of men surviving cytotoxic therapies may provide more robust risk assessment.
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PMID:Sperm DNA damage and cancer treatment. 1227 21


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