Neoplasms

All Conditions

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Rare Diseases

Paraganglioma

Hematoma, Subdural

Genetic Predisposition to Disease

Disease Susceptibility

Disease Attributes

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Paragangliomas 1

Neuroendocrine Tumor

Neuroepithelioma

Anne-Paule GIMENEZ-ROQUEPLO, MD, PhD

Alexandre BUFFET, MD, PhD

The main objective of the pilot phase of PGLEXPO will be to assess the faisability and to precise methodology of a case-control study designed for testing the impact of environmental and professional exposures on the tumoral risk in SDHx-mutation carriers

The main objective of the pilot phase of PGLEXPO will be to assess the faisability and to precise methodology of a case-control study designed for testing the impact of environmental and professional exposures on the tumoral risk in SDHx-mutation carriers.

Patients will be selected from subjects with a mutation in one of the SDHx genes. The cases will have developed a tumor, while the controls will be tumor-free. Controls will be matched to the cases according to sex, age and type of gene affected. Past exposures will be sought through a telephone questionnaire.

Impact of Environmental Exposures on Tumor Risk in Subjects at Risk of Hereditary SDHx Paraganglioma

Impact of Environmental Exposures on Tumor Risk in Subjects at Risk of Hereditary SDHx-related Paragangliomas, Pilot Phase

Individual participant data (IPD) that underlie results in publication could be shared.

Successful pairing of 50 cases with 50 controls

Proportion of cases for which a control could be identified

Mean number of controls matching for a case

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

ANSES

Assistance Publique - Hôpitaux de Paris

Swedish Mammography Cohort-clinical (SMC-C) is a clinical sub-cohort established between 2003 and 2008, consisting of 5022 women, 56-80 years of age, living in Uppsala. These women have completed a detailed questionnaire on diet and lifestyle factors and underwent a health examination, dual-energy X-ray absorptiometry and biological sampling.

The cohort of 60-years olds (60YO) was established with the aim to study CVD etiology and consists of 4,232 men and women aged 60 years who were randomly selected from Stockholm County and with baseline examination during 1 year in 1997-98. The study participants underwent a health examination, completed a questionnaire, and donated blood samples.

These are food contaminants (acrylamide, glycidol) and environmental pollutants (POPs, PFAS). Assess the associations between biomarkers of acrylamide and glycidol exposure and disease outcomes in a case-cohort study based on two prospective cohorts with biobanks. The investigators also aim to assess the exposure-affected OMICS signatures and molecular pathways underlying disease development (specifically cardiovascular diseases such as myocardial infarction and stroke and cancer such as breast-, endometrial and colorectal cancer) for these exposures along with POPs and PFAS using a prospective cohort study utilizing and integrating various 'OMICs' technologies.

Biomarkers of acrylamide, glycidol, POPs, PFAS

The aim of the project is to assess the associations between biomarkers of acrylamide and glycidol exposure and disease outcomes in a case-cohort study based on two prospective cohorts with biobanks. The investigators also aim to assess the exposure-affected OMICS signatures and molecular pathways underlying disease development (specifically cardiovascular diseases such as myocardial infarction and stroke and cancer such as breast-, endometrial and colorectal cancer) for these exposures along with persistent organic pollutants (POPs) and per- and polyflouroalkyl substances (PFAS) using a prospective cohort study utilizing and integrating various 'OMICs' technologies.

Biomarkers of Acrylamide, Glycidol, POPs, PFAS and Disease Outcomes and OMICs Signatures

Individual participant data is available from registers at Statistics Sweden and National Board of Health and Welfare in Sweden.

Using International Classification of Diseases (ICD) codes to assess cardiovascular disease (CVD) incidence (myocardial infarction and stroke, ICD10: I21 and I63)

Using ICD codes to assess cancer (such as ICD-10: C18, C20, C50, C54)

The Swedish Research Council

Karolinska Institutet

Professor

Sarcoma

Neoplasms, Connective and Soft Tissue

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Impact of Environmental Exposures on Tumor Risk in Subjects at Risk of Hereditary SDHx Paraganglioma	NCT04481152	Genetic Predisp... SDH Gene Mutati... Environmental E...		18 Years -	Assistance Publique - Hôpitaux de Paris
Biomarkers of Acrylamide, Glycidol, POPs, PFAS and Disease Outcomes and OMICs Signatures	NCT05930626	Disease Cardiovascular ... Cancer Environmental E...	Biomarkers of a...	-	Karolinska Institutet
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

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