Methods for a public health response to birth defects clusters

Few resources are available to guide public health officials in investigations of reported birth defects clusters. The majority of published resources focus on the investigation of cancer and infectious disease clusters and do not address clinical and epidemiologic concerns specific to birth defects research. This document aims to address these concerns, discuss the needs of the affected community, and provide suggestions for the development of a standardized protocol to be used as a guide in the investigation of birth defects clusters. We suggest that health departments and birth defects registries that may receive reports of birth defects clusters establish a protocol for responding that includes the following steps: develop a proactive plan for future birth defects cluster reports (step I), receive report of a birth defects cluster (step II), verify diagnoses and complete case ascertainment (step III), compare the observed rate to a reference rate (step IV), ascertain exposures among cases from available records (step V), interview case mothers (step VI), initiate further epidemiologic study-selection of controls (step VII), and communicate results to the community (step VIII). Specific criteria for continuing or terminating an investigation should be established before receiving cluster reports. The recommendations in this report should be carefully considered to ensure that the specific needs of the region, agency and affected community are met.     

Spatial Analysis of Childhood Cancer: A Case/Control Study

BackgroundChildhood cancer was the leading cause of death among children aged 1-14 years for 2012 in Spain. Leukemia has the highest incidence, followed by tumors of the central nervous system (CNS) and lymphomas (Hodgkin lymphoma, HL, and Non-Hodgkin’s lymphoma, NHL). Spatial distribution of childhood cancer cases has been under concern with the aim of identifying potential risk factors.ObjectiveThe two objectives are to study overall spatial clustering and cluster detection of cases of the three main childhood cancer causes, looking to increase etiological knowledge.MethodsWe ran a case-control study. The cases were children aged 0 to 14 diagnosed with leukemia, lymphomas (HL and NHL) or CNS neoplasm in five Spanish regions for the period 1996-2011. As a control group, we used a sample from the Birth Registry matching every case by year of birth, autonomous region of residence and sex with six controls. We geocoded and validated the address of the cases and controls. For our two objectives we used two different methodologies. For the first, for overall spatial clustering detection, we used the differences of K functions from the spatial point patterns perspective proposed by Diggle and Chetwynd and the second, for cluster detection, we used the spatial scan statistic proposed by Kulldorff with a level for statistical significance of 0.05.ResultsWe had 1062 cases of leukemia, 714 cases of CNS, 92 of HL and 246 of NHL. Accordingly we had 6 times the number of controls, 6372 controls for leukemia, 4284 controls for CNS, 552 controls for HL and 1476 controls for NHL. We found variations in the estimated empirical D(s) for the different regions and cancers, including some overall spatial clustering for specific regions and distances. We did not find statistically significant clusters.ConclusionsThe variations in the estimated empirical D(s) for the different regions and cancers could be partially explained by the differences in the spatial distribution of the population; however, according to the literature, we cannot discard environmental hazards or infections agents in the etiology of these cancers.     

Role of genetic factors in bronchial cancer. Based upon a case of anaplastic lung carcinoma in identical twins

Having observed homozygotic identical twin brothers suffering simultaneously from anaplastic bronchial cancer leading rapidly to death in both cases, the authors assessed the frequency of such cases. The available literature failed to reveal any identical observations, although four cases of twins suffering from bronchial cancer featuring different histologies (three epidermoidal and one bronchiolar-alveolar) were noted. Statistics show that, in the area where the observed twins were living, anaplastic cancer occurs each year in 0.39% of 53-year-old men. The case of these twins therefore supports the idea of the role of genetic factors in the determination of bronchial cancer.     

The interpretation of multiple-step transient-state kinetic isotope effects

In contrast to steady-state kinetic isotope effects (KIEs), transient-state tKIEs are both time and signal dependent and therefore require a very different form of theory for their interpretation. We have previously provided such a theory for the case of single-step isotopic substitutions. No such properly derived theory applicable to the analysis of multiple-step isotopic substitutions required by transient-state solvent isotope effect studies has been available up to this time. Here, we set forth a more general form of that theory which is applicable to multiple-step substituted cases. We prove three theorems: 1. the observed transient-state KIE for any given reactive component in the reaction sequence evaluated at zero time (tKIE(0)) is in fact the arithmetic product of the intrinsic KIEs of all the steps that precede the formation of that component. 2. The observed tKIE(0) is completely independent of the intrinsic KIEs of any reverse step in the reaction. 3. The intrinsic KIE of any step may be obtained by dividing the value of the tKIE(0) for that step by the value of the tKIE(0) of the immediately preceding step in the reaction sequence.     

Harmonization: Developing Consistent Guidelines for Applying Mode of Action and Dosimetry Information to Cancer and Noncancer Risk Assessment

The 1983 book, Risk Assessment in the Federal Government: Managing the Process, recommended developing consistent inference guidelines for cancer risk assessment. Over the last 15 years, extensive guidance have been provided for hazard assessment for cancer and other endpoints. However, as noted in several recent reports, much less progress has occurred in developing consistent guidelines for quantitative dose response assessment methodologies. This paper proposes an approach for dose response assessment guided by consideration of mode of action (pharmacodynamics) and tissue dosimetry (pharmacokinetics). As articulated here, this systematic process involves eight steps in which available information is integrated, leading first to quantitative analyses of dose response behaviors in the test species followed by quantitative analyses of relevant human exposures. The process should be equally appropriate for both cancer and noncancer endpoints. The eight steps describe the necessary procedures for incorporating mechanistic data and provide multiple options based upon the mode of action by which the chemical causes the toxicity. Given the range of issues involved in developing such a procedure, we have simply sketched the process, focusing on major approaches for using toxicological data and on major options; many details remain to be filled in. However, consistent with the revised carcinogen risk assessment guidance (USEPA, 1996c), we propose a process that would ultimately utilize biologically based or chemical specific pharmacokinetic and pharmacodynamic models as the backbone of these analyses. In the nearer term, these approaches will be combined with analysis of data using more empirical models including options intended for use in the absence of detailed information. A major emphasis in developing any harmonized process is distinguishing policy decisions from those decisions that are affected by the quality and quantity of toxicological data. Identification of data limitations also identifies areas where further study should reduce uncertainty in the final risk evaluations. A flexible dose response assessment procedure is needed to insure that sound toxicological study results are appropriately used to influence risk management decision-making and to encourage the conduct of toxicological studies oriented toward application for dose response assessments.     

Inflammatory bowel diseases as an intermediate stage between normal and cancer: a FTIR-microspectroscopy approach

Elucidation of the evolution of inflammatory bowel disease (IBD) to cancer by clinical symptoms and histopathology of biopsies is important. Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a diagnostic tool for distinction of normal and cancer cells and tissues. In the present work, FTIR-MSP is used to evaluate IBD cases and to study the IR spectral characteristic with respect to cancer and normal tissues from formalin-fixed colonic biopsies from patients. Specific regions of the spectra were analyzed by statistical tools to study variations in metabolites that signified changes between the two pathological conditions: IBD and cancer. IBD tissues can be grouped with cancer or normal tissue using certain parameters such as phosphate content and RNA/DNA ratio as calculated from the spectra and show intermediate levels with regard to these metabolites. Further classification of the spectra by cluster analysis indicated which cases of Crohn's disease (3 of 10 cases) or ulcerative colitis (7 of 10 cases) were more likely to progress to cancer. The study exhibits that FTIR-MSP can detect gross biochemical changes in morphologically identical IBD and cancer tissues and suggest which cases of IBD may require further evaluation for carcinogenesis.     

Cancer clusters: findings vs feelings

The issue of cancer clusters, which has been in the spotlight recently, is plagued by a wide disparity between public perceptions and scientific findings. Movies like Erin Brockovich have led the public to think that industrial pollution in the environment is causing local "cancer clusters" where cancer cases are more prevalent due to cancer-causing chemicals. There are many scientifically documented instances in which chemical exposure has caused cancer in humans, but the evidence for purely environmental exposures causing cancer is sparse. The clusters that scientists have been able to attribute successfully to a particular cause have been occupational (such as workers in a factory developing a particular type of cancer from daily exposure to a specific chemical), linked to a particular medicine, or linked to behaviors such as smoking or sunbathing. There is some indication that chemicals dissolved in drinking water may elevate the risk of gastrointestinal and bladder/urinary tract cancers and that living next to a smelter or other "point source" of air pollution may elevate risk of lung cancer. The many efforts that have been made to demonstrate links between other types of cancer and environmental contamination have not conclusively identified such links. Several challenges bedevil any cancer cluster investigation and can result in ambiguous or misleading conclusions. This report discusses the potential cancer clusters in Toms River, New Jersey and Long Island, New York, because they contain many elements typical of cancer cluster investigations and have received considerable media attention.     

Intake of fruits and vegetables,and risk of endometrial cancer in the NIH-AARP Diet and Health Study

Background: Fruits and vegetables contain a wide variety of phytochemicals which may have anti-carcinogenic effects. Although the results of case–control studies have suggested a possible protective effect of fruit and vegetable intake on the risk of endometrial carcinoma, few cohort studies have examined this association. Materials and methods: We used data from the NIH-AARP Diet and Health Study to assess the association of fruit and vegetable consumption, as well as intake of specific botanical groupings of fruits and vegetables, with endometrial cancer risk among 112,088 women who completed a food-frequency questionnaire at baseline, in 1995–1996. During 8 years of follow-up 1142 incident cases of endometrial cancer were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: After adjustment for covariates, HRs for the highest compared to the lowest quintile of total fruit and total vegetable intake were 1.30 (95% CI 1.04–1.61, P for trend 0.05) and 1.09 (95% CI 0.90–1.33, P for trend 0.55), respectively. No inverse associations were observed for intake of any of 13 botanical groupings of fruits and vegetables. Conclusions: Results from this large prospective study do not support a protective role of a high intake of fruits or vegetables on the risk of endometrial cancer in older women.     

Partner status and survival after cancer: A competing risks analysis

ObjectiveThe survival benefits of having a partner for all cancers combined is well recognized, however its prognostic importance for individual cancer types, including competing mortality causes, is less clear. This study was undertaken to quantify the impact of partner status on survival due to cancer-specific and competing mortality causes.MethodsData were obtained from the population-based Queensland Cancer Registry on 176,050 incident cases of ten leading cancers diagnosed in Queensland (Australia) from 1996 to 2012. Flexible parametric competing-risks models were used to estimate cause-specific hazards and cumulative probabilities of death, adjusting for age, stage (breast, colorectal and melanoma only) and stratifying by sex.ResultsBoth unpartnered males and females had higher total cumulative probability of death than their partnered counterparts for each site. For example, the survival disadvantage for unpartnered males ranged from 3% to 30% with higher mortality burden from both the primary cancer and competing mortality causes. The cause-specific age-adjusted hazard ratios were also consistent with patients without a partner having increased mortality risk although the specific effect varied by site, sex and cause of death. For all combined sites, unpartnered males had a 46%, 18% and 44% higher risk of cancer-specific, other cancer and non-cancer mortality respectively with similar patterns for females. The higher mortality risk persisted after adjustment for stage.ConclusionsIt is important to better understand the mechanisms by which having a partner is beneficial following a cancer diagnosis, so that this can inform improvements in cancer management for all people with cancer.     

Cimetidine and gastric cancer: preliminary report from post-marketing surveillance study.

Widespread publicity has been given to te possibility that cimetidine treatment might cause gastric cancer. Preliminary data are given from a post-marketing surveillance study in four centres. A total of 9940 patients taking the drug entered study and 9504 were observed for at least a year. Seventy-four cases of gastric cancer were identified in those taking cimetidine, but 23 of these were diagnosed before the use of the drug and 29 others with advanced malignancy had received cimetidine within the previous six months only. Ten of the remaining 22 had gastric cancer diagnosed within a year of starting treatment, and 12 after more than a year; only four of the total group had histologically "early" cancer. The occurrence of gastric cancer a long time after starting cimetidine treatment cannot be explained in every case, but it is noteworthy that in control group (which is not directly comparable) gastric cancer was observed in eight patients. The hypothesis that cimetidine treatment predisposes to gastric cancer cannot be excluded by our findings: in our view, however, they do not support such an association.     

The burden of cervical cancer in Vietnam: Synthesis of the evidence

There is currently no national cervical screening or HPV immunization program in Vietnam. This study aims to synthesize available data on the burden of disease and to project the burden of cervical cancer to 2049 if no major interventions are implemented. We reviewed published data sources on risk factors for HPV prevalence, high-grade lesions, cervical cancer incidence and mortality in Vietnam from 1990 to 2017. We then used the available data to project the number of new cervical cancer cases for the period 2013–2049. Data on cervical cancer incidence and mortality in Vietnam are limited; two Vietnamese cancer registries have been reported on by the International Agency for Research on Cancer, which cover urban populations representing ∼20% of the national population. The reported age-standardized cervical cancer incidence in Hanoi was 6.7 (1993–1997), compared to 28.8 and 14.1 per 100,000 women in Ho Chi Minh City (1995–1998 and 2009–2012, respectively). Cancer mortality data are not uniformly available from cancer registries or mortality surveys in Vietnam because cause of death has not been routinely ascertained. Based on available urban population registry data, estimated rates in the rural population, and forward projection of existing trends, we estimate that without any further intervention, the number of new cases will increase from 6930 (range 5671–8493) in 2012 to 8562 (range 5775–12,762) in 2049, giving a total of 379,617 (range 276,879–542,941) new cases over the period 2013–2049. These findings help underpin the case for the delivery of HPV vaccination and cervical screening in Vietnam, and support similar initiatives in other low- and middle-income countries.     

Cost Trend Analysis of Initial Cancer Treatment in Taiwan

Background

Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment.

Methodology/Principal Findings

The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI) system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05). Hospitalization costs comprised the largest portion of payments for all cancers. During 1996–2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05). In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share.

Conclusions/Significance

In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit from these expensive treatments.     

DNA repair gene polymorphisms and susceptibility to familial breast cancer in a group of patients from Campinas, Brazil

Several studies have reported that the genes involved in DNA repair and in the maintenance of genome integrity play a crucial role in protecting against mutations that lead to cancer. Epidemiologic evidence has shown that the inheritance of genetic variants at one or more loci results in a reduced DNA repair capacity and in an increased risk of cancer. Polymorphisms have been identified in several DNA repair genes, such as XRCC1, XPD, XRCC3, and RAD51, but the influence of specific genetic variants on repair phenotype and cancer risk has not yet been clarified. This was a case-control study design with three case groups: 53 women with breast cancer and family history; 33 women with sporadic breast cancer; 175 women with no breast cancer but with family history. The control group included 120 women with no breast cancer and no family history. The PCR-RFLP method was used to analyze the XRCC1-Arg399Gln, XPD-Lys751Gln, XRCC3-Thr241Met, and RAD51-G135C polymorphisms. No statistically significant differences were found between the case groups and the control group for any of the polymorphisms analyzed, and also between the breast cancer and family history group and the sporadic breast cancer group. Sample sizes of women with breast cancer, whether familial or sporadic, were insufficient to show any small true differences between the groups, but we have to consider that currently there is no clear consensus with respect to the association of these polymorphisms with breast cancer risk. Considering the data available, it can be conjectured that if there is any risk association between these single-nucleotide polymorphisms and breast cancer, this risk will probably be minimal. The greater the risk associated with cancer, the smaller the sample size required to demonstrate this association, and the data of different studies are usually, therefore, more concordant.     

An investigation of the sources of nonuniqueness in deterministic identifiability

While a choice of techniques exists for checking the deterministic (structural) identifiability of a specific linear, time-invariant model from a specific experiment, and some progress has been made towards topological criteria for identifiability, no method at present available allows quick and reliable checking of a range of models for globally unique identifiability from a range of experiments. Even individual cases are sometimes difficult and tedious to check. The reasons are examined by exhaustive case-by-case analysis of single-input experiments on all possible three-compartment models. All patterns of loss to the environment are covered, and all combinations of observed compartments. Catalogues of minimal observation sets for globally unique identifiability, and of nonuniquely identifiable cases, are presented. The structural causes of nonuniqueness are discussed by reference to examples from the latter catalogue. Methods are given for shortening the derivation of the structural equations giving rise to nonunique parameters. From the diversity of behavior found, it is concluded that the prospects of obtaining a comprehensive set of necessary and sufficient structural conditions for globally unique identifiability are poor.     

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n?=?23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n?=?10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n?=?7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.     

Proofreading systems of multiple stages for improved accuracy of biological discrimination

The phenomenal accuracy of biological discrimination is due in many cases to specific proofreading mechanisms. We have previously developed a macroscopic theory of such mechanisms and applied it to the case of single-stage proofreading. In this article we apply the theory to systems with multiple stages of proofreading. A specific relationship between improved accuracy due to proofreading and the associated energy cost is given. This is a macroscopic relationship that must be satisfied regardless of the details of the underlying mechanisms. Five factors in the design of such systems are shown to influence their overall accuracy: (1) initial discrimination, (2) number of proofreading stages, (3) proofreading discrimination of each stage, (4) distribution of proofreading effort among the stages, and (5) total energy expended for proofreading. We show that there is an optimal distribution of proofreading effort that, for a given degree of accuracy, minimizes the energy cost of proofreading. We also provide a simple physical interpretation of this minimum condition. These results are used to examine proofreading in two experimental systems for which there is appropriate data available in the literature: the valyl-tRNA synthetase catalyzed misacylation of tRNA^Val with threonine and the isoleucyl-tRNA synthetase catalyzed misacylation of tRNA^Ile with valine. The correlation between the magnitude of a discrimination factor and the size of the corresponding enzymatic cavity is discussed.     

Comparison of cost effectiveness of directly observed treatment (DOT) and conventionally delivered treatment for tuberculosis: experience from rural South Africa.

OBJECTIVE: To conduct an economic evaluation of directly observed treatment (DOT) and conventionally delivered treatment for the management of new cases of tuberculosis in adults. DESIGN: Community based directly observed treatment, which has been implemented in the Hlabisa district of South Africa since 1991, was compared with a conventional approach to tuberculosis treatment widely used in Africa. Each was assessed in terms of cost, cost effectiveness, and feasibility of implementation within existing resource constraints. SETTING: Hlabisa Health District, South Africa. SUBJECTS: Adult patients with new cases of tuberculosis on smear testing; the number of cases increased from 20 per month to over 100 from 1991 to 1996. MAIN OUTCOME MEASURES: Cost of case management in 1996, cost effectiveness in terms of the cost per case cured, and bed requirements in comparison with bed availability for the 1990, 1993, and 1996 caseload. Costs are expressed in US dollars at values for 1996. RESULTS: Directly observed treatment was 2.8 times cheaper overall than conventional treatment ($740.90 compared with $2047.70) to deliver. Directly observed treatment worked out 2.4-4.2 times more cost effective, costing $890.50 per patient cured compared with either $2095.60 (best case) or $3700.40 (worst case) for conventional treatment. The 1996 caseload of tuberculosis required 47 beds to be dedicated to tuberculosis to implement directly observed treatment, whereas conventionally delivered treatment would have required 160 beds; the current number of beds for tuberculosis treatment in Hlabisa is fixed at 56. CONCLUSIONS: Because of the reduced stay in hospital, directly observed treatment is cheaper, more cost effective, and more feasible than conventional treatment in managing tuberculosis in Hlabisa, given the existing hospital bed capacity and the escalating caseload due to the HIV/AIDS epidemic. Such results may hold elsewhere, and wherever conventional tuberculosis management is practised a switch to directly observed treatment will increase hospital capacity to cope with a growing caseload.     

Local Bladder Cancer Clusters in Southeastern Michigan Accounting for Risk Factors,Covariates and Residential Mobility

Background

In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation.

Methods

Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race.

Results

Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed.

Conclusion

Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of Oakland and Ingham counties, and to the City of Jackson.     

Onto-Tools,the toolkit of the modern biologist: Onto-Express,Onto-Compare,Onto-Design and Onto-Translate

Onto-Tools is a set of four seamlessly integrated databases: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Onto-Express is able to automatically translate lists of genes found to be differentially regulated in a given condition into functional profiles characterizing the impact of the condition studied upon various biological processes and pathways. OE constructs functional profiles (using Gene Ontology terms) for the following categories: biochemical function, biological process, cellular role, cellular component, molecular function and chromosome location. Statistical significance values are calculated for each category. Once the initial exploratory analysis identified a number of relevant biological processes, specific mechanisms of interactions can be hypothesized for the conditions studied. Currently, many commercial arrays are available for the investigation of specific mechanisms. Each such array is characterized by a biological bias determined by the extent to which the genes present on the array represent specific pathways. Onto-Compare is a tool that allows efficient comparisons of any sets of commercial or custom arrays. Using Onto-Compare, a researcher can determine quickly which array, or set of arrays, covers best the hypotheses studied. In many situations, no commercial arrays are available for specific biological mechanisms. Onto-Design is a tool that allows the user to select genes that represent given functional categories. Onto-Translate allows the user to translate easily lists of accession numbers, UniGene clusters and Affymetrix probes into one another. All tools above are seamlessly integrated. The Onto-Tools are available online at http://vortex.cs.wayne.edu/Projects.html.     

Postmenopausal hormone therapy and ductal carcinoma in situ: a population-based case-control study

Background and aim: The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case–control study in Connecticut, USA. Methods: This analysis included 1179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case–control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals. Results: We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.65–1.11); of estrogen alone (adjusted OR = 0.93; 95% CI: 0.68–1.29) or of estrogen and progesterone (adjusted OR = 0.75; 95% CI: 0.52–1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. Conclusions: These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data.