Combined oestrogen-progestogen replacement and breast cancer risk.
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Breast Neoplasms↗
Biomedical subjects
R Hoover
Publications and source records attributed to R Hoover.
Does chronic fatigue syndrome predispose to non-Hodgkin's lymphoma?
Chronic fatigue syndrome, an illness that frequently is associated with abnormalities of cellular immunity, has been reported anecdotally to be associated with an increased incidence of lymphoid hyperplasia and malignancy. This report describes an initial analysis of population-based cancer incidence data in Nevada, focusing on the patterns of non-Hodgkin's lymphoma prior to and subsequent to well described, documented outbreaks of chronic fatigue syndrome during 1984-1986. In a study of time trends in four age groups, the observed time trends were consistent with the national trends reported in the Surveillance, Epidemiology, and End Results Program. No statistically significant increase attributable to the chronic fatigue syndrome outbreak was identified at the state level. Additional studies are in progress analyzing the data at the country level, reviewing patterns in other malignancies, and continuing to monitor the cancer patterns over subsequent years.
Adolescent↗
Adhesion to and invasion of cultured human cells by Bartonella bacilliformis.
Bartonella bacilliformis was tested for its ability to adhere to and invade tissue culture cell monolayers. The parasite was able to efficiently bind and penetrate human dermal fibroblasts, human laryngeal epithelium, and human umbilical vein endothelial cells. Exposure of the organism to immune serum prepared against a crude Bartonella extract containing cell wall and membranous material resulted in decreased ability of the parasite to invade host cells. There was also an overall reduction in the invasiveness of bartonellae and total host cell association when human laryngeal epithelial cells and human umbilical vein endothelial cells were preexposed to cytochalasin D, indicating an active involvement of host cells in the uptake of bartonellae. Transmission electron microscopy revealed the presence of bartonellae inside and outside intracellular vacuoles. These data suggest that a surface-associated factor is involved in the invasion process and that internalization of the parasite by host cells involves a microfilament-dependent process similar to phagocytosis.
Adhesins, Bacterial↗
Endotoxin enhancement of lymphocyte adherence to cultured sheep lung microvascular endothelial cells.
The most common predisposing factor for development of the adult respiratory distress syndrome is gram-negative sepsis. Our previous studies have shown that a single infusion of Escherichia coli endotoxin into sheep causes early sequestration of lymphocytes in the lungs' microcirculation. In this report, we examined the effects of endotoxin on sheep lymphocyte adherence to sheep pulmonary microvascular endothelial cells in vitro. Endothelial cells were exposed to endotoxin, and subsequent adherence of 51Cr-labeled lymphocytes was measured in a monolayer adhesion assay. Endotoxin enhanced adherence of lymphocytes isolated from blood and caudal mediastinal node (CMN) lymph in a time- and dose-dependent manner. Adherence of CMN lymphocytes increased from a control value of 13.6 +/- 1.6% to 29.9 +/- 3.1% after 4 h of treatment with 1 microgram/ml endotoxin. Both B and T lymphocytes contributed to the increased adherence. Pretreatment of the endothelial cells with cycloheximide revealed that the endotoxin-enhanced adherence was partially dependent upon protein synthesis. Morphologic studies revealed that enhanced adherence was accompanied by a 5-fold increase in migration of lymphocytes between endothelial cells. In contrast to human umbilical vein endothelial cells, antibodies to the known lymphocyte adherence molecules, lymphocyte function-associated antigen (LFA-1), CD-44, and the lymphocyte homing receptor (LECAM-1), were ineffective in blocking adherence to the sheep pulmonary endothelial cells. We conclude that the acute sequestration of lymphocytes in the pulmonary microcirculation of sheep after endotoxin administration is due to increased adhesive properties of the endothelial cells. Our data suggest that this adherence is mediated by as yet undescribed mechanisms that may be unique to pulmonary microvascular endothelium.
Animals↗
The debrisoquine metabolic phenotype and DNA-based assays: implications of misclassification for the association of lung cancer and the debrisoquine metabolic phenotype.
Debrisoquine is an antihypertensive drug that is metabolized by cytochrome P4502D6. Deficient metabolism is inherited as an autosomal recessive condition. We previously reported in a case-control study that extensive metabolizers of debrisoquine were at greater risk of lung cancer compared to poor and intermediate metabolizers. Cloning of the gene that encodes P4502D6 (CYP2D6) led to the identification of both wild-type and mutant forms of the gene. Subsequently, a DNA-restriction fragment length polymorphism (RFLP) was identified, and a Southern hybridization-based test was developed in an attempt to define the genotype. When the DNA-RFLP test was applied to stored DNA from our study subjects there was neither a significant association with the metabolic phenotype nor an association with lung cancer. Further work has demonstrated that the wild-type gene, which was characterized by a 29-kb allele, can also contain mutations that result in nonfunctional or absent proteins. When these mutations are present, individuals exhibit the poor or intermediate metabolizer phenotype in spite of the presence of the 29-kb putative wild-type allele. Sequence determination of the mutants led to the development of techniques to exploit the polymerase chain reaction, which, together with Southern analysis, have been reported to detect as many as 95% of poor metabolizers. This technique is being used to examine the association of the extensive metabolizer genotype with lung cancer in the subjects from the case-control study. Preliminary results indicate a weak association between the homozygous wild-type genotype and lung cancer; in contrast, the extensive metabolizer phenotype is strongly associated with lung cancer in this subset.(ABSTRACT TRUNCATED AT 250 WORDS)
Case-Control Studies↗
Modulation of membrane cholesterol levels: effects on endothelial cell function.
The endothelial cell lining of blood vessels is now recognized as an active interface between blood and the underlying tissue. Modulation of cholesterol levels in several cell types has resulted in altered cell function. We have removed cholesterol from the endothelial cell membrane and have observed corresponding alterations in endothelial cell function. Following depletion of cholesterol from the endothelial cells, polymorphonuclear leukocyte adhesion to the cells was decreased. Angiotensin-converting enzyme activity of the endothelial cells was increased following removal of cholesterol from the endothelial cell membranes. The results of fluorescence polarization measurements suggest that these changes may be partially explained by altered membrane order.
Animals↗
Composition, structure, functionality, and chemical modification of legume starches: a review.
The major carbohydrate of the legume seed is starch, which represents up to 45% of the total seed weight. In recent years, substantial progress has been made in understanding the relationship between starch structure and functionality. However, these studies have been mainly on cereal and tuber starches. The present status of knowledge on the composition, structure, functionality, digestibility, and chemical modification of legume starches is reviewed. In addition present concepts of granule structure, gelatinization, retrogradation, and rheology are also reviewed. Future research needs in the area of legume starch chemistry are discussed.
Fabaceae↗
Survival in women receiving hormone replacement therapy. A record-linkage study of a large population-based cohort.
Survival was studied in a population-based cohort of over 23,000 women who were prescribed hormone replacement therapy. Complete follow-up through 1986 revealed a total of 1472 deaths, which was somewhat lower than expected; the relative survival being 101.1% (95% CL, 100.8, 101.3) after 5 years and 102.4% (95% CL, 101.9, 102.8) after 10 years. The relative survival increased with increasing age at entry into the cohort, being 98.2% (95% CL, 96.6, 99.8) in the 40-44 and 105.2% (95% CL, 101.4, 109.1) in the 65-69 year age group after 10 years. Neither the type of compound (potent vs non-potent estrogens), nor the year of entry into the cohort seemed to affect survival, whereas survival advantage generally increased with years of follow-up. Multivariate analysis showed that age at time of first prescription was the only determinant that significantly affected the death risk. This pattern could be explained by confounding due to selection of healthy subjects receiving hormone replacement therapy and/or by the specific choice of estrogen compounds (and progestogens), related to age. It is concluded that hormone replacement therapy is associated with a survival which is similar to or--notably at ages above 50-60 years--slightly higher than that in the general population.
Adult↗
Risk of cancer in women receiving hormone replacement therapy.
Cancer risk following treatment with non-contraceptive estrogens was studied in a population-based cohort of 23,244 women. Complete follow-up for an average of 6.7 years revealed 1,087 incident cancers versus 962.5 expected (relative risk/RR/ = 1.13; 95% confidence interval 1.10-1.20). We confirmed the recent findings of a more detailed analysis of the same cohort, based on a 1-year shorter follow-up period, namely: a markedly increased risk of endometrial cancer (RR = 1.8; 1.5-2.1), notably in women receiving potent estrogens, i.e., conjugated estrogens or estradiol (RR = 2.0; 1.6-2.4), and a slightly increased risk of breast cancer (RR = 1.1; 1.0-1.2). A slightly decreased risk of invasive cervical cancer (RR = 0.8; 0.5-1.2) is most likely due to more frequent smear taking than in the background population. There was no increase in the risk of cancer of ovary (RR = 1.0; 0.8-1.2), pancreas (RR = 0.8; 0.5-1.2), large bowel (RR = 1.0; 0.8-1.2) or kidney (RR = 1.0; 0.7-1.4). The risk of developing cancer in liver or biliary tract was lower than expected (RR = 0.4; 0.2-0.7), particularly in women who had used potent estrogens (RR = 0.3; 0.1-0.6), an unexpected finding which warrants further studies. Increased risks of malignant melanoma (RR = 1.5; 1.0-2.1) and lung cancer (RR = 1.3; 0.9-1.7) need cautious interpretation because of their low magnitude, the absence of a biological gradient when subgroups were analyzed and the slightly higher prevalence of smokers in the cohort than in the background population.
Climacteric↗
The risk of breast cancer after estrogen and estrogen-progestin replacement.
To examine the risk of breast cancer after noncontraceptive treatment with estrogen, we conducted a prospective study of 23,244 women 35 years of age or older who had had estrogen prescriptions filled in the Uppsala region of Sweden. During the follow-up period (mean, 5.7 years) breast cancer developed in 253 women. Compared with other women in the same region, the women in the estrogen cohort had an overall relative risk of breast cancer of 1.1 (95 percent confidence interval, 1.0 to 1.3). The relative risk increased with the duration of estrogen treatment (P = 0.002), reaching 1.7 after nine years (95 percent confidence interval, 1.1 to 2.7). Estradiol (used in 56 percent of the treatment periods in the cohort) was associated with a 1.8-fold increase in risk after more than six years of treatment (95 percent confidence interval, 0.7 to 4.6). No increase in risk was found after the use of conjugated estrogens (used in 22 percent of the treatment periods) or other types, mainly estriols (used in 22 percent of the treatment periods). Although the numbers of women were smaller, the risk of breast cancer was highest among the women who took estrogen and progestin in combination for extended periods. The relative risk was 4.4 (95 percent confidence interval, 0.9 to 22.4) in women who used only this combination for more than six years. Among women who had previously used estrogens alone, the relative risk after three years or more of use of the combination regimen was 2.3 (95 percent confidence interval, 0.7 to 7.8). We conclude that in this cohort, long-term perimenopausal treatment with estrogens (or at least estradiol compounds) seems to be associated with a slightly increased risk of breast cancer, which is not prevented and may even be increased by the addition of progestins.
Adult↗
Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype.
The risk of lung cancer in smokers was examined based on the debrisoquine metabolic phenotype and on exposure to occupational lung carcinogens, specifically asbestos and polycyclic aromatic hydrocarbons. Extensive metabolizers of debrisoquine are at a 4-fold increased risk for lung cancer compared to poor metabolizers, after adjustment for age, sex, and smoking (pack-years), when only occupationally unexposed subjects are considered. Increased risk related to the debrisoquine metabolic phenotype was greatest for squamous and small cell histologies, and least for the adenocarcinoma subtype. Men with a history of exposure to occupational carcinogens had significantly increased risk of lung cancer (relative risk = 2.8), after adjustment for age and smoking. Considering the combined effect of the high risk extensive metabolizers debrisoquine metabolic phenotype and likely occupational exposure to asbestos, the relative excess risk for lung cancer was 18-fold. This finding is consistent with a synergism in risk between the ability to extensively metabolize debrisoquine and occupational exposure to lung carcinogens in male smokers. Debrisoquine phenotyping has potential for identifying carcinogen-exposed workers at high risk of lung cancer.
Asbestos↗
Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study.
OBJECTIVE: To determine the relative risk of developing endometrial neoplasia after treatment with oestrogens alone or in conjunction with progestogens. DESIGN: Prospective cohort follow up study, average observation period 5.7 years for each patient. To have a 90% chance of detecting a relative risk of 2.0 with 95% significance the study required 78,000 person years of observation. SETTING: Community based cohort. PATIENTS: Women aged over 35 who were prescribed non-contraceptive oestrogens in the Uppsala health care region during April 1977 to March 1980 were identified from pharmacy records. Of all prescriptions issued, 95% were identified. Patients from the cohort who developed endometrial neoplasia were identified from the cancer registry of the Uppsala health care region. Compliance, sociodemographic data, and lifetime exposures to oestrogen and cyclically added progestogen were assessed by questionnaire in a sample of the cohort. The final cohort consisted of 23,244 patients (133,373 person years). The prevalence of university education, oophorectomy, and hysterectomy was higher in the cohort than the general population; no other confounding factors were identified. MEASUREMENTS: The total number of person years was divided into exposure groups by inference from the data from the questionnaire. Compensation was made for the excess of hysterectomies. Specimens from all cases of endometrial neoplasia in the cohort and 90% of cases in the general population were studied blind histopathologically. Characteristics of treatment of all women who had endometrial neoplasia were assessed by questionnaire. Relative risks and 95% confidence intervals were calculated. RESULTS: Seventy four cases of carcinoma and 33 cases of premalignant lesions occurred in the cohort. The relative risk of endometrial carcinoma was 1.8 (95% confidence interval 1.1 to 3.2) after exposure to any oestrogen compound without progestogen for more than six years; 2.2 (1.2 to 4.4) after more than three years' exposure to conjugated oestrogens without progestogen; and 2.7 (1.4 to 5.1) after more than three years' exposure to oestradiol compounds without progestogen. When carcinoma and premalignant lesions were considered together the results were similar but the relative risk was higher. Risk of carcinoma did not increase when progestogens were cyclically added to oestrogens for the entire treatment period (relative risk 0.9 (0.4 to 2.0]. CONCLUSIONS: Use of oestrogens without progestogens is associated with a twofold to threefold increase in risk of endometrial neoplasia. Use of progestogens either removes this increased risk or delays its onset. A further follow up of the cohort is essential to analyse the risks with greater statistical power.
Adult↗
In vitro effects of endotoxin on bovine and sheep lung microvascular and pulmonary artery endothelial cells.
A single infusion of Escherichia coli endotoxin into sheep results in structural evidence of pulmonary endothelial injury, increases in both prostacyclin and prostaglandin E2 (PGE2) in lung lymph, and an increase in pulmonary microvascular permeability. Endotoxin-induced lung endothelial damage can also be induced in vitro, but to date these studies have utilized endothelium from large pulmonary vessels. In the present study, we have grown endothelial cells from peripheral lung vessels of cows and sheep and exposed these microvascular endothelial cells to endotoxin. Controls included lung microvascular endothelium without endotoxin and endothelial cells from bovine and sheep main pulmonary artery with and without addition of endotoxin. We found that endotoxin caused significant increases in release of prostacyclin and PGE2 from both bovine and sheep lung microvascular and pulmonary artery endothelium. Normal bovine and sheep pulmonary artery and bovine lung microvascular endothelium released greater levels of prostacyclin than PGE2 (ng/ng); release of PGE2 from the microvascular cells was greater than from the pulmonary artery endothelium in both species. Exposure of endothelial cells from cow and sheep main pulmonary artery to endotoxin results in endothelial cell retraction and pyknosis, a loss of barrier function, increased release of prostacyclin and PGE2 and eventual cell lysis. In lung microvascular cells, the increases in prostanoids were accompanied by changes in cell shape but occurred in the absence of either detectable alterations in barrier function or cytolysis. Thus, while endotoxin causes alterations to endothelial cells from both large and small pulmonary vessels, the effects are not identical suggesting site specific phenotypic expression of endothelial cells even within a single vessel. To determine whether the response of either the large or small pulmonary vessel endothelial cells in culture mimics most closely the in vivo response of the lung to endotoxin requires further study.
Animals↗
A case-control study of epithelial ovarian cancer.
With data from a study of 296 patients with primary epithelial ovarian cancer and 343 patients hospitalized because of other conditions, we estimated ovarian cancer risk in accordance with reproductive and other factors. Risk was greatest among women of lower parity, especially among women who said they planned to have children but could not. The protective effect of oral contraceptives seen in other studies was observed only in subgroups of our study population. Women who had breastfed their children had decreased risk, but the number of months of breastfeeding was not related to risk. Incomplete pregnancies did not provide the protection seen for live births. A family history of ovarian cancer and a medical history of breast cancer were both strong risk factors. None of the nonreproductive factors that we examined, including childhood illnesses, tobacco and alcohol consumption, obesity, and selected adult diseases, was convincingly associated with risk.
Adult↗
Cancer risk following pernicious anaemia.
A computer-based file of all Veterans Administration (VA) hospitalisation records for the period 1969-1985 was used to identify and follow for cancer development a cohort of 5,161 white males with pernicious anaemia. A total of 34,915 person-years were accrued, with an average length of follow-up of 6.8 years. A total of 481 cancers were diagnosed, slightly higher than the number expected (SIR = 1.2). Significant excesses were observed for cancers of the buccal cavity and pharynx (1.8) and stomach (3.2), and for melanoma (2.1), multiple myeloma (2.1), myeloid leukaemia (3.7) and other and unspecified leukaemia (4.0). Although the excess for stomach cancer was highest in the first year after diagnosis in a VA hospital, risks of 2-fold or greater persisted throughout the study period. The majority of leukaemias occurred in the first year of follow-up, but some excess risk continued beyond this time. The elevated risk of buccal and pharyngeal cancers may relate to heavy alcohol intake among this population, although risks remained high even when the cohort was restricted to patients without an admission for alcoholism. Although an elevated risk of stomach cancer among pernicious anaemia patients is consistent with most previous surveys, the low absolute risk suggests that the cost-effectiveness of intensive screening should be reassessed.
Adolescent↗
Cancer risk after evaluation for infertility.
To evaluate cancer risk by various causes of infertility, the authors conducted a retrospective cohort study among 2,335 women evaluated for infertility at the Mayo Clinic between 1935 and 1964. Most cancers occurred at expected frequencies, with the exception of cancers of the thyroid (standardized incidence ratio (SIR) = 2.6) and other endocrine glands (SIR = 6.7), although analyses were based on small numbers. Patients with progesterone deficiencies (31 per cent of the study subjects) had a 20 per cent higher cancer risk than did those with other causes of infertility, with excesses deriving primarily from cancers of the lung, cervix, ovary, and thyroid and from melanoma. Breast cancer risk, however, was not elevated in either patients with progesterone deficiencies (SIR = 0.9) or patients with other causes of infertility (SIR = 1.0). Examination of other parameters of infertility, including age at evaluation, type of infertility (primary vs. secondary), and years of attempted conception, showed no elevated risks of breast cancer in any subgroup. These results fail to support previous studies that have linked progesterone deficiencies among infertile women to elevated breast cancer risk. However, the data suggest a possible involvement of a progesterone deficiency in the etiology of other cancers, particularly thyroid cancer and melanoma.
Adult↗
Effects of timing and type of tobacco in cigarette-induced bladder cancer.
We analyzed a case-control study of bladder cancer in Torino (512 male and 55 female cases; 596 male and 202 female controls) with emphasis on the timing of cigarette smoking and the use of black or blond tobacco. The risk of bladder cancer was 2 to 3 times higher among smokers of black tobacco than among smokers of blond tobacco. Both groups of smokers showed a beneficial effect of smoking cessation, with an immediate decline in risk. This pattern is consistent with a late-stage effect of smoking. Among smokers of black tobacco, there was a gradient of risk with early exposure, and smokers who had quit never showed a drop to base-line levels of risk. These patterns, not apparent in users of blond tobacco, suggest an early stage effect of black tobacco, perhaps due to the higher concentration of aromatic amines in black than blond tobacco smoke and the higher blood levels of the hemoglobin adduct with 4-aminobiphenyl (a human bladder carcinogen) among smokers of black tobacco.
Age Factors↗
Menopause and ovarian cancer.
Using data from a study of 296 patients diagnosed in greater Washington, D.C., from 1978 to 1981 with primary epithelial ovarian cancer and 343 patients hospitalized for other conditions, the authors estimated the rate ratios according to various characteristics of the menopause. Menopause induced by hysterectomy with preservation of both ovaries was associated with a 30 per cent reduction in risk of later development of ovarian cancer. Age at natural menopause was not consistently related to risk. Women who used menopausal estrogens showed a 40 per cent decreased risk.
Actuarial Analysis↗