Local action of estrogen and thyroid hormone on vasoactive intestinal peptide (VIP) and galanin gene expression in the rat anterior pituitary.

Neuropeptides act within the pituitary as autocrine or paracrine factors, modulating the synthesis and release of primary pituitary hormones, and possibly regulating cell proliferation and/or plasticity. Manipulation of the endocrine status of rats produces dramatic long-term changes in the pituitary expression of several peptides, including the neuropeptides galanin and vasoactive intestinal peptide (VIP). Whether or not these changes are caused indirectly by hypothalamic factors, or by hormone actions directly in the pituitary, has been only partially addressed. To determine if estrogen or thyroid hormone can act directly within the pituitary to regulate VIP and galanin gene expression, cultured female rat pituitary cells were treated with 10 nM 1,17 beta-estradiol (E2) or triiodothyronine (T(3)). E2 treatment for three days resulted in an approximate 5-fold and 7-fold increase in VIP and galanin mRNA, respectively. In contrast, T(3) treatment reduced the mRNA levels of these neuropeptides to approximately 40% and 30% of control values. A time course study indicated that the actions of estrogen on VIP and galanin mRNA, and of thyroid hormone on VIP mRNA were readily apparent after 24h. The rat pituitary tumor cell line RC-4B/C was found to express easily detectable levels of galanin but not VIP mRNA. Galanin gene expression in these cells was moderately increased by E2 and decreased by T(3). Transfection of a series of luciferase plasmids containing 5 kb to 131 bp of the bovine galanin promoter fused to luciferase revealed cell-type specific enhancer sequences located between -452 and -131 bp of the galanin gene transcription start site. However, transfected plasmids were minimally responsive to E2 and T(3) treatment. Overall the results suggest that E2 and T(3) exert significant local actions in the pituitary on VIP and galanin gene expression. The bovine galanin gene fragment used in these studies contains a potential pituitary cell-type specific enhancer, but appears to lack strong E2-and T(3)-responsive sequences.

Occupation and female papillary cancer of the thyroid.

This article presents the joint results of two Swedish case-control studies regarding occupational exposure and female papillary thyroid cancer. Questionnaires inquiring about lifetime occupations and specific occupational exposures were mailed to cases and controls, aged 20 to 70 years. Some 185 female papillary or mixed cancer cases and 426 female controls were included in the analysis. Increased risks were seen for women who had worked as a dentist/dental assistant, teacher, shoemaker, or warehouse worker. In addition, occupational contacts with undefined chemicals, x-rays, or video display terminals were indicated as risk factors.

Levels of selenium in plasma and glutathione peroxidase in erythrocytes in patients with prostate cancer or benign hyperplasia.

Plasma selenium and glutathione peroxidase in erythrocytes were analysed in a case-control study encompassing 164 cases with prostate cancer and 152 controls with benign prostate hyperplasia. Plasma selenium levels were divided into three groups; I > 1.17, II 1.00-1.17 and III < 1.00 mumol/l. For the 124 cases with no supplementary intake of selenium pills, the mean plasma selenium level was 0.99 (range 0.27-1.47) and for the corresponding 121 controls 1.08 (range 0.52-1.50) mumol/l, a difference which was significant (P = 0.0007). The three categories of selenium levels had odds ratios (OR) of 0.3 and a 95% confidence interval (CI) of 0.1-0.7 for group I, an OR of 0.6 and a CI of 0.3-1.1 for group II, and group III was used as the reference entity. No significant differences in levels of glutathione peroxidase in erythrocytes were found between cases and controls.

Metaanalysis of 4 Swedish case-control studies on exposure to pesticides as risk-factor for soft-tissue sarcoma including the relation to tumor-localization and histopathological type.

In four previous case-control studies we have shown an association between exposure to phenoxyacetic acids or chlorophenols and soft-tissue sarcoma (STS). These chemicals are contaminated by dioxins and dibenzofurans, some of which are known carcinogens in experimental animals. In a meta-analysis of our four studies we studied such exposure including the relation to tumour localization and histopathological type of STS. In total 434 histopathologically verified STS cases and 948 controls were included. Anatomical tumour localization was assessed by scrutinizing medical records for all cases. In the analysis stratification was made for age, vital status and study. Significantly increased risks were obtained for exposure to phenoxyacetic acids and chlorophenols, odds ratios 2.7 and 3.3, 95% confidence intervals 1.9-4.7 and 1.8-6.1, respectively. The increased risk was independent of histopathological subtype and anatomical site although especially high odds ratios were obtained for body sites close to areas where dermal contact may occur in sprayers. Phenoxyacetic acids and chlorophenols with their contaminating dioxins and dibenzofurans should be regarded as carcinogenic for STS regardless of tumour localization and histopathological type.

Thyroid cancer: reproductive factors, previous diseases, drug intake, family history and diet. A case-control study.

An association between female sex hormones and thyroid cancer has been suggested, but the only well-established risk factor is ionizing radiation. This case-control study was designed to evaluate the association between different aetiological factors and thyroid cancer and encompassed 180 cases aged 20-70 years at the time of diagnosis in 1980-89, and 360 controls. The response rate was 92%. A history of one pregnancy gave increased risk for papillary thyroid cancer, odds ratio (OR) = 3.1, 95% confidence interval (CI) = 1.0-11, whereas no increased risk was found for > or = four pregnancies. Age > or = 25 years at the time of the first pregnancy showed a non-significantly increased risk for papillary thyroid cancer, OR = 1.5, 95% CI = 0.8-3.0. Use of oral contraceptives before the age of 20 years gave an OR of 0.5, 95% CI = 0.1-1.3. A history of asthma or allergy, or the use of cortisone, significantly decreased the risk, while cardiovascular disease in men increased the risk of developing thyroid cancer. In the logistic regression, use of cortisone decreased the risk, while one pregnancy gave a significantly increased risk in papillary thyroid cancer. The results indicated that endogenous hormones may play a role in the aetiology of thyroid cancer in women.

Medical diagnostic and therapeutic ionizing radiation and the risk for thyroid cancer: a case-control study.

The aim of this study was to investigate exposure to diagnostic and therapeutic ionizing radiation as a risk factor for thyroid cancer. This case-control study encompassed 180 women and men with thyroid cancer, aged 20-70 years at the time of diagnoses in 1980-89. From the National Population Registry 360 controls were selected. The response rate was 95% for the cases and 90% for the controls. Thyroid radiation dose from medical and dental X-ray examinations was divided into three categories. The highest exposure category (> 0.59 mGy) yielded an odds ratio (OR) for women < or = 50 years of age of 2.7 with 95% confidence interval (CI) of 1.2-6.6. OR increased to 4.9 (CI = 1.6-16) if papillary cancer alone was considered in this age group. For women aged > 50 years and for men no significantly increased risks were seen. External radiotherapy yielded OR = 3.1 (CI = 0.9-12) and for women only OR = 4.9 (CI = 1.1-24). In papillary thyroid cancer, logistic regression gave increased risk for X-ray examinations with a thyroid dose > 0.59 mGy (OR = 2.7, CI = 1.0-6.9) and for external radiotherapy (OR = 2.7, CI = 0.4-16). No increased risk was found for exposure to 131I. The findings in this study indicated an association between diagnostic or therapeutic radiation and thyroid cancer in women, but may have been influenced by recall bias.

Exposure to phenoxyacetic acids, chlorophenols, or organic solvents in relation to histopathology, stage, and anatomical localization of non-Hodgkin's lymphoma.

Results on 105 cases with histopathologically confirmed non-Hodgkin's lymphoma (NHL) and 335 controls from a previously published case-control study on malignant lymphoma are presented together with some extended analyses. No occupation was a risk factor for NHL. Exposure to phenoxyacetic acids yielded, in the univariate analysis, an odds ratio of 5.5 with a 95% confidence interval of 2.7-11. Most cases and controls were exposed to a commercial mixture of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Exposure to chlorophenols gave an odds ratio of 4.8 (2.7-8.8) with pentachlorophenol being the most common type. Exposure to organic solvents yielded an odds ratio of 2.4 (1.4-3.9). These results were not significantly changed in the multivariate analysis. Dichlorodiphenyltrichloroethane, asbestos, smoking, and oral snuff were not associated with an increased risk for NHL. The results regarding increased risk for NHL following exposure to phenoxyacetic acids, chlorophenols, or organic solvents were not affected by histopathological type, disease stage, or anatomical site of disease presentation. Median survival was somewhat longer in cases exposed to organic solvents than the rest. This was explained by more prevalent exposure to organic solvents in the group of cases with good prognosis NHL histopathology.

Levels of cadmium, zinc and copper in renal cell carcinoma and normal kidney.

Levels (microgram/g dry weight) of cadmium (Cd), zinc (Zn) and copper (Cu) were determined in kidneys with renal cell carcinoma from 20 male and 11 female patients. Autopsied kidneys from nine males and eight females who had died of nonmalignant diseases were used as controls. The mean levels in cortex of Cd was in cases 103.2 and in controls 79.9 (not significantly different). For non-smoking cases, mean level of Cd in cortex was somewhat lower than in the controls. No significant differences were found between cases and controls for Cd levels in the medulla. Zn in cortex was significantly lower in the cases aged > or = 69 years (mean 182.0) than in the corresponding controls (mean 237.6). Zn in medulla was significantly lower in all cases (mean 103.5) than in controls (mean 162.2). The mean level of Cu in the medulla in cases was 10.7 and in controls 13.0 (P = 0.05). No differences were found for Cu levels in cortex.

Occupational exposures and thyroid cancer: results of a case-control study.

A case-control study on thyroid cancer concerning 180 cases and 360 controls aged 20-70 years at diagnosis was performed. Both females and males were included. Of the cases, 63% had had papillary thyroid cancer. Work with diagnostic X-ray investigations constituted a risk factor for thyroid cancer of the papillary type yielding an odds ratio (OR) of 2.9 with 95% confidence interval (CI) = 1.1-8.3. For women only OR was 3.3 (CI = 1.2-9.8). The results also indicated that work as a lineman, which entails exposure to electromagnetic fields and chemicals, increased the risk. Exposure to impregnating agents gave an increased OR = 2.8 with CI = 1.0-8.6. For men only OR was 3.8 with CI = 1.1-16. Women who were previously smokers and female current smokers had significantly decreased risks with OR = 0.5 (CI = 0.2-0.96) and OR = 0.6 (CI = 0.3-0.96), respectively.