asmaa HA mohamed, PHD

amal RA ibrahim, lecturer

amal RA Ibrahim, lecturer

aml AL mohamed, lecturer

detection of DNA damage due to occupational exposure to low dose ionizing radiation using comet assay technique and genotyping of certain DNA repair genes to detect inherited polymorphism.

Assessment of DNA Damage Due to Ionizing Radiation

Assessment of DNA Damage and Capacity of DNA Repair System Among Nuclear Medicine and Clinical Oncology Workers Exposing to Ionizing Radiation

Assiut University

Director, clinical research

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Skin Neoplasms

Skin Diseases

SSW Works, is a virtual learning environment (VLE) for automated, comprehensive, on-demand, tailored distribution of the SSW program to private and public employers with outdoor workers. It will be delivered in both English and Spanish to managers and employees who work outdoors to reduce risk for skin cancer.

Workplaces randomized to the control condition will receive a set of printed materials on occupational sun safety (1 mailing per year) as an attention control. These will include posters on personal protection and skin cancer incidence, risk assessment brochure, American Academy of Dermatology SPOT bookmark showing the ABCDEs of melanoma and skin self-examination, and a sun safety tip card from OSHA.

SSW Works is a behavioral, culturally tailored online intervention for skin cancer prevention amongst outdoor workers in the United States.

SSW Works

Provision of online materials for skin cancer prevention.

Minimal Information Control

Mary Buller, MA

Americans who work outdoors are exposed to an extreme amount of solar ultraviolet radiation over a lifetime that substantially increases their risk for developing skin cancer. In Phase I, the feasibility of a virtual learning environment (VLE) for distributing the effective Sun Safe Workplaces (SSW) intervention to American employers will be established with input from senior managers and Hispanic and African American outdoor workers and development and evaluation of a prototype of the SSW Works VLE. In Phase II, the full SSW Works will be produced and tested for effectiveness at improving outdoor workers' sun protection in a randomized trial enrolling employers nationwide.

Americans who work outdoors are exposed to an extreme amount of solar ultraviolet radiation (UV) over a lifetime that substantially increases their risk for developing skin cancer. Annually, skin cancer is diagnosed in over 3.5 million U.S. adults, melanoma kills nearly 7,000 Americans, and treatment costs at least $8 billion. The U.S. Surgeon General has identified occupational sun safety as a national priority. The team has spent the past two decades developing a successful comprehensive approach to occupational sun protection in 5 trials funded largely by the National Cancer Institute. Sun Safe Workplaces (SSW) combines policy and education to increase workplace actions on sun safety and employee sun protection practices. In this SBIR Fast-Track application, the investigators will develop a virtual learning environment (VLE), SSW Works, to distribute the SSW program to American workplaces. It will be comprised of a database, content management (interactive toolbox), and media platform (trackable training) that tailors the SSW program to management's readiness to innovate on sun safety based Diffusion of Innovations Theory. SSW Works will better integrate SSW into safety training by improving appropriateness for Hispanic and African American workers and conforming with the latest learning management systems technology (LMS). Strong scientific premise comes from the published literature and the team's 5 previous studies that demonstrated SSW is feasible and effective in public works, public safety, and outdoor recreation workplaces. The Phase I specific aims will establish the feasibility of SSW Works by 1) creating and validating an algorithm to tailor resources and implementation strategies to employers' stages in the diffusion of innovations process; 2) identifying unique attitudes, barriers, and practices related to sun safety among Hispanic and African American employees in focus group discussion and adjusting the SSW content; and 3) creating a prototype of the SSW Works VLE, including inputs, staging algorithm and tailored report, employee training compatible with a popular LMS, and storyboards of brief videos for managers and employees and testing it for feasibility and usability with managers and Hispanic and African American outdoor workers, and confirming that the training can operate within a popular LMS. In Phase II, SSW Works will be fully programmed and tested for effectiveness by achieving the specific aims of: 1) producing the full SSW Works, in English and Spanish, for distribution of the evidence-based SSW and 2) conducting a randomized controlled trial with 20 workplaces evaluating impact of SSW distributed over the SSW Works on employees' sun safety practices (primary outcome). The primary hypothesis is: compared to employers in the minimal information control group, employers assigned to receive SSW Works will have employees that practice more sun protection at posttest. The SBIR Fast-Track research is significant and innovative. SSW Works will have high impact and commercial potential because outdoor workforce is large and at very high risk for skin cancer, improving sun safety will reduce health care costs and save lives, and there are few commercial competitors.

Virtual Sun Safe Workplaces Ph II (SSW Works)

SSW Works: A Virtual Learning Environment for Occupational Skin Cancer Prevention Ph II

Employees will report frequency of sun protection at work (i.e., sunscreen with SPF 30+, long-sleeved shirts, long pants, hat with wide-brim, sunglasses, shade use, limit midday sun exposure, and have sunscreen, hat and eye protection at all times \[1=never, 5=always\]). SPF 30+ is advised in SSW to account for typical under-application that reduces effective SPF.

Employees will report prevalence of sunburn in past 3 months on the job (yes/no; number).

National Cancer Institute (NCI)

Klein Buendel, Inc.

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Cases (incident patients with a diagnosis of primary sarcoma and histologically confirmed by an expert pathologist of the RRePS or ResOs networks in the 15 districts of France participating to this study) Environmental, occupational and lifestyle-related exposures

Subjects never diagnosed with a primary sarcoma and individually-matched by sex, age (5-years group), and districts of residence and randomly selected from electoral list.

Environmental, occupational and lifestyle-related exposures

A standardized questionnaire will be administered by a trained interviewer in order to gather information about occupational and residential history, demographic and socioeconomic characteristics and lifestyle factors. At the end of the interview, a saliva sample will be systematically proposed

Environmental, occupational and lifestyle-related exposures

Aude Lacourt, PhD

Brice Amadéo, PhD

Loïc CHAIGNEAU

Antoine ITALIANO

Thierry FABRE

Corinne DELCAMBRE LAIR

Nicolas PENEL

Carlos MAYNOU

Fabrice FIORENZA

Valérie LEBRUN-LY

Jean-Yves BLAY

Isabelle RAY-COQUARD

Didier CUPISSOL

François GOUIN

Emmanuelle BOMPAS

Jean-Emmanuel Kurtz

Antonio DI MARCO

Axel LE CESNE

Gilles MISSENARD

Introduction: Sarcomas are rare tumors of connective tissue. The exact overall incidence of sarcomas is unknown due to diagnostic difficulties and the various histological subtypes (over 80 subtypes). However, the apparent increasing incidence of sarcomas suggests environmental causes such as pesticides. Except for some specific factors (i.e. ionizing radiation, vinyl chloride, dioxin, and genetic predispositions) the scientific knowledge on the aetiology of sarcomas is sparse and inconsistent. France is a particularly appropriate country to set up a study investigating the causes of sarcoma occurrence due to the French organization in treatment and care of sarcoma patients, which is highly structured and revolved around national expert networks. The main objective of the ETIOSARC project is to study the role of lifestyle, environmental and occupational factors in the occurrence of sarcomas among adults from a multicentric population-based case-control study.

Methods and analysis: Cases will be all incident cases (older than 18 years old) identified in 15 districts of France covered by a cancer registry and/or a reference center in sarcoma's patient care over a three-year period with an inclusion start date ranging from the 1st October 2018 to the 1st January 2020 and histologically confirmed by a second review of the diagnosis. Two controls will be individually-matched by sex, age (5-years group), and districts of residence and randomly selected from electoral list. A standardized questionnaire will be administered by a trained interviewer in order to gather information about occupational and residential history, demographic and socioeconomic characteristics and lifestyle factors. At the end of the interview, a saliva sample will be systematically proposed.

This study will permit to validate or not already suspected risk factors for sarcomas such as phenoxyherbicides, chlorophenol and to generate new hypothesis to increase our understanding about the genetic and environmental contributions in the carcinogenicity process.

The main objective of the ETIOSARC study is to assess the role of lifestyle, environmental and occupational factors in the occurrence of sarcomas among adults from a multicenter population-based case-control study.

Specific objectives are:

* To identify environmental risk factors for sarcomas as a whole and for the most frequent subtypes;
* To investigate the interactions between gene polymorphisms and environmental exposures in sarcoma susceptibility;
* To assess whether some specific genetic characteristics of sarcoma' tumors are associated with environmental exposures; We will also explore the feasibility of classifying sarcomas by genetics types (simple vs complex genomic profile) as part of the objective of identifying environmental risk factors.

Study design

The ETIOSARC study is a prospective multicenter population-based case-control study. This study is restricted to French geographical areas (further called districts) that meet at least one of these four criteria:

* Criteria 1: Districts covered by both a general cancer registry and a French Sarcoma Group (GSF-GETO) expert center from either the network of reference for soft-tissue sarcoma pathology (RRePS), the network of reference for bone sarcoma pathology (ResOs) or the clinical sarcoma network (NetSarc);
* Criteria 2: Districts including a coordinator center of any of the RRePS / NetSarc networks;
* Criteria 3: Districts covered by a general cancer registry that is expected to register more than 50 cases per year;
* Criteria 4: Districts adjacent to districts meeting criteria 1 and covered by a general cancer registry.

In total, 15 districts meet one of the four criteria, which represent approximatively 24% of the French population (2015 estimations from the national institute of statistics and economic studies, Insee). Nine districts meet criteria 1 (Gironde, Hérault, Haute-Vienne, Loire Atlantique, Calvados, Nord, Bas-Rhin and Doubs, Poitou-Charentes), two districts meet criteria 2 (Rhône and Val-de-Marne); two districts meet criteria 3 (Isère and Haut-Rhin) et two districts meet criteria 4 (Manche, Vendée).

Study population

Cases recruitment modalities

Patients will be recruited by specifically trained clinical research associate (CRA). In districts where a general cancer registry is active, the process of identifying incident sarcoma patients is well defined, which warrants the efficiency and exhaustiveness of the recruitment. However, poor survival for some cancer cases will not allow to rely on routine inclusion procedure and the registries will implement a rapid case ascertainment procedure to minimize the delay between diagnosis and enrollment and interview. Cases will be identified from pathology laboratories and multidisciplinary sarcoma tumor board (including sarcoma, gynecological, digestive, skin and bone tumor board). CRA will regularly contact laboratories and hospitals (within a three months window) to identify newly diagnosed sarcoma cases and to collect associated reports. The CRA will retrieve the clinical file in order to check inclusion and non inclusion criteria and to collect names and addresses of eligible patients and their physicians. Then, the CRA will contact the case's physicians in order to gather their clinical advice to include their patients in the study. In case of agreement, the CRA will contact the patients and ask them to participate. In case of oral agreement, he/she will arrange an interview to collect written consent and administer detailed questionnaire.

In Rhône and Val de Marne where no general cancer registry exists, the process of identifying incident sarcoma patients will largely rely on the existence of a RRePS/ResOS/NetSarc coordination center to facilitate the identification of new cases.

Regardless of the district, the diagnosis of all included cases will be systematically ascertained by an expert pathologist within the RRePS and ResOs networks following a standard procedure.

On a regular basis (at least once a month), the list of incident cases included in the RRePS/ResOS/NetSarc networks will be extracted from the shared databases. The list of cases identified by registries will be merged with the list of cases included in the RRePS/ResOS/NetSarc networks by the pathology sample reference number in order to collect diagnosis confirmation and to identify new but missed incident cases.

Controls selection

The selection of controls and the recruitment of cases will take place simultaneously. Every time a case will be diagnosed and identified, two controls will be randomly selected at that time from the electoral rolls of the same district as the case district of residence. For each case, a list of 20 potential controls with the same age (within a 5-year age group) and sex as the cases will be constituted in order to account for potential refusal. Calls to contact potential controls will be centralized and will be made by an investigator specifically trained to better understand the objectives of the study. First, this investigator will try to retrieve the phone number of the first potential control on the list and will contact him/her in order to gather his/her agreement to participate in this study. After five calls made at different schedules (e.g. in the evening on weekdays), if the potential control couldn't be reached, the investigator will send an information letter containing a reply coupon indicating phone number and schedule at which the person could be reach. If the reply coupon is not returned, or after 10 calls made at the phone number and the schedule indicated on the reply coupon, the first potential control will be considered as unreachable and then, the same procedure will be applied for the second potential controls on the list and so on until two controls per case agreed to participate to the study.

For each control agreeing to participate, an appointment will be made to collect written consent and to administer detailed questionnaire by a CRA.

All participants will give their informed written consent to participation, in line with French ethical guidelines.

Data collection

Data will be collected from self-questionnaire supplemented by a specific questionnaire. The self-questionnaire will permit to gather the complete occupational history (for each job held for at least 6 months) and residential history (for each place occupied for at least 6 months). During a face-to-face interview, the trained interviewer will check (complete if necessary) and supplement the self-administered questionnaire by a specific questionnaire with questions about demographic and socioeconomic characteristics, occupations of spouse and parents, leisure-time activities, reproduction, medical history, family history of cancer, diet, lifestyle factors such as tobacco smoking and alcohol consumption. The specific questionnaire will also collect additional occupational and residential information such as work tasks, work places, materials handled for each job held for at least 6 months and description of the environment of each residence places.

At the end of the interview, subjects (both cases and controls) will be invited to provide a saliva sample in order to obtain germline DNA.

In case of refusal to participate and if the subject agreed, data on demographic and socioeconomic characteristics will be collected in order to assess the potential selection bias that might occur due to the specific profile of non-respondent subjects.

Biological sampling and storage

Each participant will be asked to provide a salivary sample in order to obtain germline DNA. Salivary samples will be collected by the subjects themselves under instructions from the CRA, using DNA Genotek Oragene 575 collection kit. After collection, samples will be sent at the Biological Resources Center of the Bordeaux hospital university center "Bordeaux Biothèque Santé" for storage.

Determination of the sample size

Since our definition of environmental exposures is very broad, the sample size calculation has been based on various scenarios of exposure prevalence, from 5% (relevant for domestic, environmental but also some occupational exposures such as farmer in the general population) to 20% (relevant for some occupational exposures such as fibers). For a total sample size of 2000 cases and a 1:2 individually-matched design, considering a statistical power of 80% at a significance level of 5%, the minimum detectable odds ratio will be 1.39 and 1.21 under a exposure prevalence of 5% and 20%, respectively. Considering sub-types analyses, the four main histological types are GIST, liposarcoma, leiomyosarcoma and unclassified sarcoma, which account for 18%, 15%, 11% and 16% of sarcomas, respectively. Considering a sample size of 300 cases, the minimum detectable odds ratio will be 2.21 and 1.61 under an exposure prevalence of 5% and 20%, respectively. Typically in environmental epidemiology, the relative increases in disease risks due to environmental exposures are usually low around 1.5, thus, it is essential to recruit a minimum of 2000 cases in order to be able to perform sub-type analyses.

Statistical analysis

Relationship between case/control status and each exposure variable and 95% confidence intervals will be individually estimated using conditional logistic regression models. If necessary, a multilevel logistic model will be implemented in order to take into account the data variability due to the multicenter design and the various CRA that will administer the questionnaires.

Stratified histological sub-types analyses are also planned. Moreover, since sarcomas may be classified into four groups on a molecular basis (i.e. sarcomas with recurrent translocation, sarcomas with specific activating or inactivating mutations, sarcomas with MDM2 amplifications, and sarcomas with a complex genomic profile), the feasibility of classifying sarcomas by genetic types instead of by histological subtypes for the objective of identifying environmental risk factors will be explore. The underlying hypothesis is that the aetiology among these four molecular groups may be homogeneous.

Methods for coordinating the project and for quality control

This study is organized around three different centers or committees: a national coordination center, a steering committee, and local centers.

The national coordination center will be in charge of running routine operations, assisting participating local centers, guaranteeing the quality of the data collection, centralizing data, supervising the data coding and exposure assessment.

The steering committee's principal role will be to establish research priorities based on the availability of the data and the current scientific knowledge.

Local centers will be in charge of determining identification sources of cases in their districts and of collecting data. They will also transmit the collected data to the national coordination center.

Standardized procedures are written in a procedure manual to guarantee the quality of the collected data. Besides, a completion guide of the standardized questionnaire has been developed to assist CRA during interviews. A data manager will ensure that the study is conducted in compliance with the protocol. On a regular basis and as frequently as necessary, he/she will assess the quality of the collected data using several indicators: the average time spent by the CRA at the subject's home, the degree of completeness of the questionnaires by CRA, the ratio of included cases to expected cases, the average elapsed time between the identification of a case and the interview, the average elapsed time between case and control interviews, etc.

All collected data will be centralized in a single location, the University of Bordeaux (CREDIM, centre de Recherche et de Développement en Informatique Médicale).

Each participant will be asked to provide a salivary sample in order to obtain germline DNA. Salivary samples will be collected by the subjects themselves under instructions from the CRA, using DNA Genotek Oragene 575 collection kit. After collection, samples will be sent at the Biological Resources Center of the Bordeaux hospital university center "Bordeaux Biothèque Santé" for storage.

Etiosarc: Environmental Aetiology of Sarcomas From a Multicenter French Population-based Case-control Study Among Adults

Etiosarc: Study of the Environmental Aetiology (Environment, Occupations and Lifestyle) of Sarcomas (Soft Tissue, Visceral and Bone) From a Multicenter French Population-based Case-control Study Among Adults.

Anonymized individual participant data for both cases and controls will be made available under request to the principal investigator

The relationship between case/control status and each exposure variable will be estimated by odds ratios and their 95% confidence intervals using conditional logistic regression models.

Institut National de la Santé Et de la Recherche Médicale, France

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Tin Miners in China at risk of lung cancer

Christian Abnet, Ph.D.

The overall goal of this project is to identify strategies to reduce lung cancer incidence and mortality. Using a high-risk occupational cohort, our specific objectives are 1) to establish a biologic specimen bank and data bank that can be used for the validation and refinement of potential early markers of lung cancer, and 2) to establish a cohort for the study of environmental (including dietary) and genetic risk factors for lung cancer.

Lung cancer is the leading cause of death from malignant neoplasms in the United States and in many countries around the world. Potential strategies to reduce the incidence and mortality of lung cancer include new methods of early detection and identification and alteration of etiologic factors.

The Yunnan Tin Corporation (YTC), located in Yunnan Province in southern China, is a large, nonferrous-metals industry, formed in 1883 and nationalized after the establishment of the People's Republic in 1949. It is involved principally in the production of tin from the mines around the city of Gejiu. The tin miners at YTC have extremely high rates of lung cancer. Among those at high risk, defined as miners 40+ years old with 10+ years of underground mining and/or smelting experience, more than one percent per year develop lung cancer. These extraordinary lung cancer rates result from combined exposure to radon, arsenic, and tobacco smoking in the form of cigarettes and/or bamboo water pipe.

The study population for the development of a biologic specimen bank for the study of early markers of lung cancer is all YTC miners considered to be at high risk for lung cancer based on their occupation exposure (40+ years old with 10+ years of underground or smelting experience). Currently numbering over 7,000, this high-risk group has been the target for the annual lung cancer screening program at the YTC for the past 20+ years. For each high-risk miner, sputum samples are collected annually, read for cytologic interpretation, and stored in Saccomanno's solution for future early marker research. Screening chest x-rays are also obtained. Subjects are followed annually to determine if any have developed lung cancer. Diagnostic workup of suspicious cases includes an additional sputum sample and histology specimen(s), which are used for diagnostic purposes and also retained for future research.

Additional biologic specimens have also been obtained on screenees for etiologic research, including a one-time collection of whole blood, urine, and toenail clippings. Finger stick bloods and buccal smears for DNA will also be sought.

Development of a Biologic Specimen Bank for the Study of Early Markers of Lung Cancer Among Tin Miners in Yunnan, China

usual infusion practices (neutral solvent-purged infusers)

Safe infusion device is a different method than usual infusion practices (neutral solvent-purged infusers)

Safe Infusion Device

Monocentric comparative before / after study to evaluate the efficacy of Safe Infusion Devices (SIDs) in reducing drug exposure to nurses compared to usual perfusion practices.

Despite the decreasing of environmental contamination throughout the anticancer drug circuit, the administration of chemotherapies remains at risk of occupational exposure for nurses. Many medical devices aim at securing administration, but none have been scientifically evaluated to verify the actual improvement.

A monocentric comparative before / after study was carried out in an oncology day hospital in order to evaluate the efficacy of Safe Infusion Devices in reducing drug exposure compared to usual perfusion practices (neutral solvent-purged infusers). The rate of nurses' gloves contamination was estimated. The eligible protocols must contain at least one disconnection step and one of the 10 drugs screened. To avoid false negatives, each sample of gloves was contaminated with a drop of topotecan. Association between contamination and other variables was investigated using a multivariate regression analysis.

The usual practice leaded to a rate of 58.3% of contaminated samples while Safe Infusion Devices to a rate of 15%: Safe Infusion Devices reduced the risk of gloves contamination by 84% in multivariate analysis (Odds ratio=0.16; 95% confidence interval=0.05-0.47; p\<0.001). Topotecan was identified within 100% of the samples. Only one case of cross-contamination has occurred.

Despite the current practice of using neutral solvent-purged infusers, the occupational exposure remains high for nurses and Safe Infusion Devices significantly reduced this risk of exposure. However, glove contamination is only a surrogate endpoint. The results confirmed that the disconnection of empty bags resulted in occupational exposure. Except a contamination due to the leakage of a bag, no cross-contamination was detected. This validated the environmental quality of the cytotoxic drug circuit. Safe Infusion Devices were highly effective but did not completely eliminate exposure.

Safe Infusion Device in Reducing Occupational Exposure of Nurses

Evaluation of a Safe Infusion Device in Reducing Occupational Exposure of Nurses to Antineoplastic Drugs: a Comparative Prospective Study. CONTAMOINS-1

The statistical unit consists of a sample taken from all the gloves used for the administration of a daily course. The dosing assay allowed to identify a panel of 10 cytotoxic drugs (HPLC MS/MS).

The dosing assay allowed to identify a panel of 10 cytotoxic drugs (HPLC MS/MS).

For each daily course performed in 2017 requiring the intravenous route, the necessary devices were estimated according to the two strategies

The manufacturing time was defined as the time elapsed between the time of passage in the cleanroom and the end of manufacturing of the first drug of the course.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Assessment of DNA Damage Due to Ionizing Radiation	NCT03240172	Occupational Ex...		-	Assiut University
Virtual Sun Safe Workplaces Ph II (SSW Works)	NCT05774600	Skin Cancer Occupational Ex...	SSW Works Minimal Informa...	18 Years -	Klein Buendel, Inc.
Etiosarc: Environmental Aetiology of Sarcomas From a Multicenter French Population-based Case-control Study Among Adults	NCT03670927	Sarcoma Environmental E... Occupational Ex... Life Style	Environmental, ...	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
Development of a Biologic Specimen Bank for the Study of Early Markers of Lung Cancer Among Tin Miners in Yunnan, China	NCT00340405	Lung Cancer		40 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Safe Infusion Device in Reducing Occupational Exposure of Nurses	NCT04102332	Cancer	Safe Infusion D...	18 Years -	Institut de Cancérologie de la Loire
Assessment of DNA Damage Due to Ionizing Radiation	NCT03240172	Occupational Ex...		-	Assiut University

Spots Global Cancer Trial Database for occupational exposure