scholarly journals Ethylene Oxide: Cancer Evidence Integration and Dose–Response Implications

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581988831 ◽  
Author(s):  
Melissa J. Vincent ◽  
Jordan S. Kozal ◽  
William J. Thompson ◽  
Andrew Maier ◽  
G. Scott Dotson ◽  
...  
Keyword(s):  
Ethylene Oxide ◽  
Dose Response ◽  
The United States ◽  
Epidemiological Studies ◽  
International Agency ◽  
Breast Cancers ◽  
Early Effect ◽  
Human Carcinogen ◽  
Increased Risk ◽  
Toxicological Studies

The International Agency for Research on Cancer (IARC) and the United States Environmental Protection Agency (USEPA) classified ethylene oxide (EtO) as a known human carcinogen. Critically, both noted that the epidemiological evidence based on lymphoid and breast cancers was “limited,” but that the evidence in animal studies was “sufficient” and “extensive” (respectively) and that EtO is genotoxic. The USEPA derived one of the highest published inhalation unit risk (IUR) values (3 × 10−3 per [µg/m3 EtO]), based on results from 2 epidemiological studies. We performed focused reviews of the epidemiological and toxicological evidence on the carcinogenicity of EtO and considered the USEPA’s reliance on a genotoxic mode of action to establish EtO’s carcinogenicity and to determine likely dose–response patterns. Higher quality epidemiological studies demonstrated no increased risk of breast cancers or lymphohematopoietic malignancies (LHM). Similarly, toxicological studies and studies of early effect biomarkers in animals and humans provided no strong indication that EtO causes LHM or mammary cancers. Ultimately, animal data are inadequate to define the actual dose–response shape or predict tumor response at very low doses with any confidence. We conclude that the IARC and USEPA classification of EtO as a known human carcinogen overstates the underlying evidence and that the IUR derived by USEPA grossly overestimates risk.

The “Moscow signal” epidemiological study, 40 years on

2019 ◽  
Vol 34 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Jose A. Martínez
Keyword(s):  
Health Status ◽  
Epidemiological Study ◽  
Electromagnetic Fields ◽  
The United States ◽  
Epidemiological Studies ◽  
International Agency ◽  
Department Of State ◽  
Foreign Service ◽  
Human Carcinogen ◽  
Radiofrequency Electromagnetic Fields

Abstract Between 1953 and 1979, the USSR irradiated the United States embassy in Moscow with microwaves. This episode, a classic Cold War affair, has acquired enormous importance in the discussions on the effect of non-ionizing radiation on people’s health. In 2011, the International Agency for Research on Cancer (IARC) classified radiofrequency electromagnetic fields as being a possible human carcinogen (Group 2B), but the results of recent laboratory and epidemiological studies have led some researchers to conclude that radiofrequency electromagnetic fields should be reclassified as a human carcinogen instead of merely a possible human carcinogen. In 1978, the “Moscow signal” case was officially closed after the publication of the epidemiological study of (Lilienfeld AM, Tonascia J, Tonascia S, Libauer CA, Cauthen GM. Foreign Service health status study. Evaluation of health status of foreign service and other employees from selected Eastern European posts. Report on Foreign Service Health Status Study, U.S. Department of State 6025-619073, 1978.), showing no apparent evidence of increased mortality rates and limited evidence regarding general health status. However, several loose ends still remain with respect to this epidemiological study, as well as the affair as a whole. In this paper, we summarize the available evidence concerning this case, paying special attention to the epidemiological study of Lilienfeld et al. After reviewing the available literature (including declassified documents), and after some additional statistical analyses, we provide new insights which do not complete the puzzle, but which may help to better understand it.

Physical Activity, Sedentary Behaviors, and Risk of Cancer

2017 ◽  
Author(s):  
Steven C. Moore ◽  
Charles E. Matthews ◽  
Sarah Keadle ◽  
Alpa V. Patel ◽  
I-Min Lee
Keyword(s):  
Physical Activity ◽  
The United States ◽  
Moderate Intensity ◽  
Activity Levels ◽  
Breast Cancers ◽  
Sedentary Behaviors ◽  
Moderate Intensity Physical Activity ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Risk Of Cancer

Current physical activity guidelines recommend that adults perform at least 150 minutes per week of moderate-intensity physical activity (e.g., brisk walking), or 75 minutes per week of vigorous-intensity activity (e.g., jogging), or an equivalent combination of these. In the United States and worldwide, many adults fail to meet these recommended activity levels, with deleterious consequences for health, including increased risk of some cancers. This chapter reviews the epidemiologic evidence for links between physical activity and cancer, emphasizing published meta-analyses and the results of a recent large consortium-based study. The authors find the evidence to be convincing that physical activity reduces risk of colon and female breast cancers, and probable that it reduces risk of kidney and endometrial cancers. Moreover, physical activity has been associated with lower risk of cancers of the bladder, liver, gastric cardia, head and neck, esophagus (adenocarcinoma), and myeloma, myeloid leukemia, and non-Hodgkin lymphoma.

scholarly journals A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

2013 ◽  
Vol 2013 ◽  
pp. 1-53 ◽  
Author(s):  
Katherine von Stackelberg
Keyword(s):  
Systematic Review ◽  
The United States ◽  
Epidemiologic Studies ◽  
Potential Interaction ◽  
Disease Etiology ◽  
Modes Of Action ◽  
Increased Risk ◽  
Toxicological Studies ◽  
Bioassay Data ◽  
2,4 Dichlorophenoxyacetic Acid

Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin’s disease (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

scholarly journals Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Claudia Consales ◽  
Caterina Merla ◽  
Carmela Marino ◽  
Barbara Benassi
Keyword(s):  
Oxidative Stress ◽  
Electromagnetic Fields ◽  
Childhood Leukemia ◽  
Low Frequency ◽  
Epidemiological Studies ◽  
Data Uncertainty ◽  
International Agency ◽  
Neuroprotective Effects ◽  
Great Debate ◽  
Increased Risk

Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system.

scholarly journals The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

2021 ◽  
Vol 23 (1) ◽  
pp. 424
Author(s):  
Chiara Chiodo ◽  
Catia Morelli ◽  
Fabiola Cavaliere ◽  
Diego Sisci ◽  
Marilena Lanzino
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Estrogen Receptor Α ◽  
Epidemiological Studies ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Increased Risk ◽  
The Impact

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.

scholarly journals Global Consultation on Cancer Staging: To Promote Consistent Understanding and Use of Cancer Stage Terminology

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 151s-151s
Author(s):  
B. O'Sullivan ◽  
F. Moraes ◽  
S.H. Huang ◽  
M. Malcolm ◽  
J. Brierley ◽  
...  
Keyword(s):  
Cancer Control ◽  
Cancer Staging ◽  
Cancer Registries ◽  
The United States ◽  
Cancer Surveillance ◽  
International Agency ◽  
Cancer Stage ◽  
Disease Extent ◽  
Increased Risk ◽  
Staging Systems

Background and context: Although the TNM stage schema has been the traditional means to classify anatomic extent of disease, in recent years confusion and uncertainty have emerged which underpinned by lack of familiarity concerning underlying rules of staging and their application. In turn such lack of clarity has led increased risk of miscommunication regarding patient care, research, cancer surveillance, epidemiology and cancer control. The UICC TNM Committee has confirmed a lack of uniformity in the application of cancer stage and its rules. In addition to stage, numerous other factors influence the outcome of patients as relate to tumor characteristics, patient descriptors, and the environment where any treatment is administered. A particularly a frequent problem is mixing disease extent and biology which has promoted additional misunderstanding about the importance and relevance of different individual prognostic elements and to what degree biology vs disease burden contribute to outcome. Aim: To ensure uniformity of staging systems, rules and classifications, the TNM Committee developed a global consensus on cancer staging. Strategy/Tactics: A selected literature review of twelve high impact oncology journals was performed and results will be summarized. There was inconsistent understanding and use of cancer stage classification terminology evident in up to 20% of the literature. A survey was developed and found that only 12.5% of those surveyed thought that the application of the TNM staging terminology was consistent and uniform in the literature. Respondents believed that complete T, N and M data should be recorded in cancer registries, 71% considered that other predictive and prognostic factors should also be collected by central cancer registries but that anatomic disease extent should be collected as a separate variable (85%). The Global Consultation on Cancer Staging was held under the auspices of the Union for International Cancer Control (UICC) and Lancet Oncology with support from the United States (US) National Cancer Institute (NCI) and the US Centers for Disease Control and Prevention (CDC). Experts from these organizations and FIGO (Fédération Internationale de Gynécologie et d´Obstétrique), IACR (International Association of Cancer Registries), IARC (International Agency for Research in Cancer), and the ICCR (International Collaboration on Cancer Reporting) attended. Program/Policy process: The purpose of the staging classification was reaffirmed. Important issues about staging processes were annunciated, and inconsistencies in terminology and use were acknowledged. Definitions of frequently misused staging terms were clarified. What was learned: It was determined that methodologies need to be explored to identify and include necessary data elements relevant to personalized treatment. Selection of factors should particularly include attention to their inclusion in cancer registries where appropriate.

scholarly journals Intermediate Effect Biomarkers--Alternatives to Direct Concentration- Response Data for Regulatory Benefits Analyses

2011 ◽  
Vol 4 (1) ◽  
pp. 70-77
Author(s):  
Dale Hattis
Keyword(s):  
Birth Weight ◽  
Fetal Growth ◽  
Dose Response ◽  
Air Pollutants ◽  
Epidemiological Studies ◽  
Hazardous Air Pollutants ◽  
End Effects ◽  
Early Effect ◽  
Response Data ◽  
Public Health Protection

Perceived needs for extensive chemical-specific toxicological information have impeded efforts to assess risks and evaluate likely public health protection benefits of possible standards for hazardous air pollutants (HAPs). This paper discusses opportunities to use effects of HAPs on early effect biomarkers, such as birth weights, to predict likely changes in rare quantal effects of concern that would be relevant for the quantification of likely regulatory benefits from exposure reductions. In the birth weight example, even modest exposures to common air pollutants can be seen as producing a kind of tax on the limited resources available to the fetus to grow and develop. In contrast to teratogenic effects, dose response relationships for fetal growth restriction in animals are often nearly linear, suggesting that the developing fetus may not generally have untapped ”functional reserve capacity“ that is expected to buffer the effects of modest exposures to toxicants in the traditional toxicological paradigm. Given this mechanistic perspective, supported in part by parallel dose response relationships between reported cigarette smoking and both birth weight and infant mortality, restriction on fetal growth can be associated with changes in quantal end effects of concern that are more difficult to assess directly in epidemiological studies.

Issues in Breast Cancer Survivorship: Optimal Care, Bone Health, and Lifestyle Modifications

2016 ◽  
pp. e22-e29
Author(s):  
Michelle E. Melisko ◽  
William J. Gradishar ◽  
Beverly Moy
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Bone Health ◽  
Breast Cancer Survivors ◽  
Care Delivery ◽  
Large Population ◽  
The United States ◽  
Breast Cancers ◽  
Lifestyle Modifications ◽  
Increased Risk

There are an estimated 3.1 million survivors of breast cancer in the United States. The predominant reasons for this substantially large population are that breast cancer is the most common noncutaneous malignancy among women and that 5-year survival rates after breast cancer treatment are approximately 90%. These patients have many medical considerations, including the need to monitor for disease recurrence and to manage complications of their previous cancer treatments. Most patients remain at risk indefinitely for local and systemic recurrences of their breast cancers and have an increased risk of developing contralateral new primary breast cancers. Therefore, optimizing care for this patient population is critical to the overall health care landscape in the United States. Here, we summarize survivorship care delivery and its challenges, the optimization of bone health in breast cancer survivors, and opportunities for risk reduction through lifestyle modifications.

scholarly journals Injury threshold of oral contact with hot foods and method for its sensory evaluation

2018 ◽  
Author(s):  
Dirk W. Lachenmeier ◽  
Walter Lachenmeier
Keyword(s):  
Contact Time ◽  
Food Product ◽  
Epidemiological Studies ◽  
Contact Temperature ◽  
International Agency ◽  
Threshold Values ◽  
Test Technique ◽  
Risk Of Injury ◽  
Increased Risk ◽  
Risk Of Cancer

Epidemiological studies indicate an increased risk of cancer from the consumption of very hot foods and beverages. The International Agency for Research on Cancer (IARC) has already recommended threshold values for the maximum drinking temperature of very hot beverages. The contact time and the contact temperature are decisive for the risk of injury when hot media come into contact with human skin. However, measuring the contact temperature is not easily possible in practice. In the present study, a numerical simulation based on the solution of the heat conduction equation was initially used to investigate whether and for what period of time a constant contact temperature is to be expected under oral conditions. For small circular 3-cm food samples (e.g., cooked potatoes) with 2.5 mm thickness in contact with the tongue, the simulation results in a constant contact temperature of 10 s before cooling. With a thickness of 0.5 mm, the contact temperature is only maintained 1 s. Hot beverages, which spread as a thin film and thereby increase their surface area, can therefore be consumed at higher temperatures than solid foods. Furthermore, a simple test technique with a "measuring spoon" was developed. A hot sample is placed on the tongue. Orientating measurements were used to determine which contact temperature was considered to be just comfortable for any period > 10 s and for which period of less than 10 s it was still just bearable. The contact temperature, which was still perceived as tolerable for periods > 10 s, was 46.5 °C. The time spans for the higher contact temperature 48 °C were between 2 and 4 s and for 49 °C between 1 and 2 s. The course of the contact temperatures determined in the experiment over time allows to calculate the corresponding threshold values of consumption temperatures for various foods. Consumption temperatures of about 56 °C for potatoes and 60 °C for cheese are still perceived as tolerable. In view of the fact that the contact temperature is obviously the determining factor for the risk of injury from burns in the oral cavity in addition to the contact time, it makes sense to reference threshold values to the contact temperature rather than to the surface or consumption temperature of a food product, which is current customary practice. If this contact temperature is defined as a threshold value, the surface or consumption temperature for any other food can be calculated.

Ductal Carcinoma In Situ: Challenges, Opportunities, and Uncharted Waters

2012 ◽  
pp. 40-44 ◽  
Author(s):  
Abigail W. Hoffman ◽  
Catherine Ibarra-Drendall ◽  
Virginia Espina ◽  
Lance Liotta ◽  
Victoria Seewaldt
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
The United States ◽  
Targeted Prevention ◽  
Breast Cancers ◽  
Increased Risk

Overview: Ductal carcinoma in situ (DCIS) is a heterogeneous group of diseases that differ in biology and clinical behavior. Until 1980, DCIS represented less than 1% of all breast cancer cases. With the increased utilization of mammography, DCIS now accounts for 15% to 25% of newly diagnosed breast cancer cases in the United States. Although our ability to detect DCIS has radically improved, our understanding of the pathophysiology and factors involved in its progression to invasive carcinoma is still poorly defined. In many patients, DCIS will never progress to invasive breast cancer and these women are overtreated. In contrast, some DCIS cases are clinically aggressive and the women may be undertreated. We are able to define some of the predictors of aggressive DCIS compared with DCIS of low malignant potential. However, our ability to risk-stratify DCIS is still in its infancy. Clinical risk factors that predict aggressive disease and increased risk of local recurrence include young age at diagnosis, large lesion size, high nuclear grade, comedo necrosis, and involved margins. Treatment factors such as wider surgical margins and radiation therapy reduce the risk of local recurrence. DCIS represents a key intermediate in the stepwise progression to malignancy, but not all aggressive breast cancers appear to have a DCIS intermediate, notably within triple-negative breast cancer. Ongoing studies of the genetic and epigenetic alterations in precancerous breast lesions (atypia and DCIS) as well as the breast microenvironment are important for developing effective early detection and individualized targeted prevention.

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