Improving Scientists'Judgments of Risk

Scientists disagree in their risk analyses because they use intuitive judgments to generalize results from the laboratory to circumstances not yet studied. If this assertion is correct, techniques intended to reduce intuitive judgments and increase analytical cognition should reduce scientific dispute. The results of a test case involving allegedly high risk and sharp dispute among scientists are described.     

Extending the Stochastic Two-Stage Model of Carcinogenesis to Include Self-Regulation of the Nonmalignant Cell Population

One of the challenges of introducing greater biological realism into stochastic models of cancer induction is to find a way to represent the homeostatic control of the normal cell population over its own size without complicating the analysis too much to obtain useful results. Current two-stage models of carcinogenesis typically ignore homeostatic control. Instead, a deterministic growth path is specified for the population of "normal" cells, while the population of "initiated" cells is assumed to grow randomly according to a birth-death process with random immigrations from the normal population. This paper introduces a simple model of homeostatically controlled cell division for mature tissues, in which the size of the nonmalignant population remains essentially constant over time. Growth of the nonmalignant cell population (normal and initiated cells) is restricted by allowing cells to divide only to fill the "openings" left by cells that die or differentiate, thus maintaining the constant size of the nonmalignant cell population. The fundamental technical insight from this model is that random walks, rather than birth-and-death processes, are the appropriate stochastic processes for describing the kinetics of the initiated cell population. Qualitative and analytic results are presented, drawn from the mathematical theories of random walks and diffusion processes, that describe the probability of spontaneous extinction and the size distribution of surviving initiated populations when the death/differentiation rates of normal and initiated cells are known. The constraint that the nonmalignant population size must remain approximately constant leads to much simpler analytic formulas and approximations, flowing directly from random walk theory, than in previous birth-death models.(ABSTRACT TRUNCATED AT 250 WORDS)     

Re-Figuring Marked Bodies on the Borders: Breast Cancer and “Femininity”

The author discusses writings by Eve Kosofsky Sedgwick, Kathleen Martindale, Audre Lorde, and Barbara Rosenblum on their experiences with breast cancer, and explores their articulations of the impact mastectomy has had on their sense of femininity in relation to their own identities and body images, and in relation to cultural expectations, and how others perceive them. Their identification of the body as socially produced, and as a site of contestation and multiple struggles, offers a strategic site from which to engage with the violent gender-inflected notion of the ideal female body. Themes addressed include: the process of writing embodied experience to make it real, the body's role in the process of identity formation, the culturally constructed significance of appearance to the individual's sense of femininity, the value of the female body in a capitalistic society, and heterosexism in society and in the health care system.     

Stochastic Estimates of Exposure and Cancer Risk from Carbon Tetrachloride Released to the Air from the Rocky Flats Plant

Carbon tetrachloride is a degreasing agent that was used at the Rocky Flats Plant (RFP) in Colorado to clean product components and equipment. The chemical is considered a volatile organic compound and a probable human carcinogen. During the time the plant operated (1953-1989), most of the carbon tetrachloride was released to the atmosphere through building exhaust ducts. A smaller amount was released to the air via evaporation from open-air burn pits and ground-surface discharge points. Airborne releases from the plant were conservatively estimated to be equivalent to the amount of carbon tetrachloride consumed annually by the plant, which was estimated to be between 3.6 and 180 Mg per year. This assumption was supported by calculations that showed that most of the carbon tetrachloride discharged to the ground surface would subsequently be released to the atmosphere. Atmospheric transport of carbon tetrachloride from the plant to the surrounding community was estimated using a Gaussian Puff dispersion model (RATCHET). Time-integrated concentrations were estimated for nine hypothetical but realistic exposure scenarios that considered variation in lifestyle, location, age, and gender. Uncertainty distributions were developed for cancer slope factors and atmospheric dispersion factors. These uncertainties were propagated through to the final risk estimate using Monte Carlo techniques. The geometric mean risk estimates varied from 5.2 x 10(-6) for a hypothetical rancher or laborer working near the RFP to 3.4 x 10(-9) for an infant scenario. The distribution of incremental lifetime cancer incidence risk for the hypothetical rancher was between 1.3 x 10(-6) (5% value) and 2.1 x 10(-5) (95% value). These estimates are similar to or exceed estimated cancer risks posed by releases of radionuclides from the site.     

Environmental Tobacco Smoke Revisited: The Reliability of the Data Used for Risk Assessment

Several epidemiological studies have found a weak, but consistent association between lung cancer in nonsmokers and exposure to environmental tobacco smoke (ETS). In addition, a purported link between such exposure and coronary heart disease (CHD) has been of major concern. Although it is biologically plausible that ETS has a contributory role in the induction of lung cancer in nonsmoking individuals, dose-response extrapolation-supported by the more solid database for active smokers-gives an additional risk for lung cancer risk that is more than one order of magnitude lower than that indicated by major positive epidemiological studies. The discrepancy between available epidemiological data and dosimetric estimates seems, to a major part, to reflect certain systematic biases in the former that are difficult to control by statistical analysis when dealing with risks of such low magnitudes. These include, most importantly, misclassification of smoking status, followed by inappropriate selection of controls, as well as certain confounding factors mainly related to lifestyle, and possibly also hereditary disposition. A significant part of an association between lung cancer and exposure to ETS would disappear, if, on the average, 1 patient out of 20 nonsmoking cases had failed to tell the interviewer that he had, in fact, recently stopped smoking. In the large International Agency for Research on Cancer (IARC) multicenter study even lower misclassification rates would abolish the weak, statistically nonsignificant associations that were found. In the former study an apparent significant protective effect from exposure to ETS in childhood with respect to lung cancer later in life was reported, a most surprising finding. The fact that the mutation spectrum of the p53 tumor suppressor gene in lung tumors of ETS-exposed nonsmokers generally differs from that found in tumors of active smokers lends additional support to the notion that the majority of tumors found in ETS-exposed nonsmokers have nothing to do with tobacco smoke. The one-sided preoccupation with ETS as a causative factor of lung cancer in nonsmokers may seriously hinder the elucidation of the multifactorial etiology of these tumors. Due to the high prevalence of cardiovascular disease in the population, even a modest causal association with ETS would, if valid, constitute a serious public health problem. By pooling data from 20 published studies on ETS and heart disease, some of which reported higher risks than is known to be caused by active smoking, a statistically significant association with spousal smoking is obtained. However, in most of these studies, many of the most common confounding risk factors were ignored and there appears to be insufficient evidence to support an association between exposure to ETS and CHD. Further, it seems highly improbable that exposure to a concentration of tobacco smoke at a level that is generally much less than 1% of that inhaled by a smoker could result in an excess risk for CHD that-as has been claimed-is some 30% to 50% of that found in active smokers. There are certainly valid reasons to limit exposure to ETS as well as to other air pollutants in places such as offices and homes in order to improve indoor air quality. This goal can be achieved, however, without the introduction of an extremist legislation based on a negligible risk of lung cancer as well as an unsupported and highly hypothetical risk for CHD.     

Frequentist and Bayesian approaches for a joint model for prostate cancer risk and longitudinal prostate-specific antigen data

The paper describes the use of frequentist and Bayesian shared-parameter joint models of longitudinal measurements of prostate-specific antigen (PSA) and the risk of prostate cancer (PCa). The motivating dataset corresponds to the screening arm of the Spanish branch of the European Randomized Screening for Prostate Cancer study. The results show that PSA is highly associated with the risk of being diagnosed with PCa and that there is an age-varying effect of PSA on PCa risk. Both the frequentist and Bayesian paradigms produced very close parameter estimates and subsequent 95% confidence and credibility intervals. Dynamic estimations of disease-free probabilities obtained using Bayesian inference highlight the potential of joint models to guide personalized risk-based screening strategies.     

Preoperative sexual status of Japanese localized prostate cancer patients: comparison of sexual activity and EPIC scores

Objective: This study aimed to evaluate the relationship between sexual activity and sexual function using questionnaires distributed to middle-aged Japanese patients with localized prostate cancer.

Methods: A total of 145 patients who underwent radical prostatectomy were enrolled in the survey reported on herein. Sexual activity and sexual function were investigated via the Expanded Prostate Cancer Index Composite (EPIC) and an original self-reported questionnaire.

Results: Of participants, 24.1% and 20.7% had sexual activity within a month period as investigated via the EPIC and original questionnaire, respectively. However, 29.7% of all those who reported sexual activity rate reported “about once every 2?months to a year,” as shown in the original questionnaire. Regarding sexual function as addressed through EPIC, no results within that questionnaire’s measure of sexual function showed significant differences among patients with a rate of actual sexual activity.

Conclusions: The present survey showed that more than quarter of preoperative middle-aged Japanese prostate cancer patients surveyed had actual sexual activity, though not within the preceding 4?weeks. To precisely evaluate sexual function of middle-aged Japanese patients, it is necessary to consider actual sexual activity.     

Listening to the Voices of Lesbians Diagnosed with Cancer

Abstract

This paper focuses on the operations of heterosexism and strategies to counter it in a particular service context: the context of psychosocial support services for women with cancer. The paper draws on findings from a participatory, qualitative study set in Ontario, Canada in which 26 lesbians were interviewed about their experiences of cancer diagnosis, treatment, health care and social support, and their feelings and perceptions about shifts in identity, body, sexuality and relationships. This paper focuses on findings related to the changes research participants perceived as necessary in the provision and organization of cancer support services, in order to increase access and ensure equity for lesbians with cancer and their families.     

Prostatic diseases in the senescence: structural and proliferative features

Senescence is one of the main aetiological factors which are responsible for natural androgen ablation in men and occurrence of prostatic diseases. However, it is unclear how the prostatic lesions are signallised in the prostate. Thus, the aim of this study is to characterise the structural, the ultrastructural and the proliferative aspects of the peripheral prostatic zone in the elderly men with and without diagnoses of prostatic lesions and with potential precursors of prostate cancer. Sixty samples of prostatic tissue, from 60 to 90-year-old patients with and without lesions obtained from autopsied or prostatectomised patients were divided into four groups (15 samples per group): standard group (no lesions), benign prostatic hyper-plasia group, high-grade prostatic intra-epithelial neoplasia group and prostatic carcinoma group. The samples were submitted to morphometrical, structural and ultrastructural analyses in addition to cellular apoptosis and proliferative analyses. The results showed morphological damages in the stroma and cellular organelles involved in the secretory process of the prostate. Moreover, the prostatic lesions in elderly men demonstrated disturbance in the proliferation/apoptosis rate, indicating a prevalence of the proliferative process. Finally, the imbalance in prostatic stroma-epithelium interaction was a harmful feature in the elderly men as a result of structural changes, which are crucial factors for the development and progression of carcinogenesis.     

Body mass index and functional status in community dwelling older Turkish males

Abstract

Objectives: To assess sex hormones in men with obesity and prostate cancer (PCa) and to study association between androgens and the pathogenesis biology of PCa in vitro.

Subjects and methods: One hundred and eighty-one men older than 45?years selected from of a population attending to Urology departments screening for PCa, (78 participants without PCa and 103 patients with PCa). All participants were assessed for body mass index (BMI), age, Gleason score, and PSA. Endocrine profile was determined for LH, total testosterone (TT), 17β-estradiol (E2), prolactin and leptin. Biochemical profile (HbA1c, triacylglycerols and lipoproteins) was also determined. In vitro experiments were also performed, involving the study of 5α-dihydrotestosterone (DHT) and E2 in the presence of adipocyte-conditioned medium (aCM).

Results: All variables were continuous and described a Gaussian distribution unless mentioned. To determine the relation of aggressiveness, variable were transformed into categories. Thus, PCa aggressiveness is associated with the increase of age and BMI (p?<?.0001) but with is decreased with TT and E2 (p?<?.05). Moreover, adipocyte-secreted molecules increase aggressiveness of PCa cells in vitro. Lastly, DTH but not E2 enables invasiveness in vitro.

Conclusions: It was observed a coexistence of hormone axis profile alteration with sex hormones and BMI in PCa patients, in accordance with the new perspective of PCa pathogenesis.