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

NCT03670927 | Completed DMC

• 1 other identifier: C17-03
• Study Type: observational
• Target: 2,237
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Sarcoma; Environmental Exposure; Occupational Exposure; Life Style

Outcome Measures

Primary Outcomes (1)

• Odds ratios measuring the association between environmental exposures under study (environmental, occupational and lifestyle exposures) and sarcoma occurence

  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.

  1 year

Study Arms (2)

Cases

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

Other: Environmental, occupational and lifestyle-related exposures

Controls

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

Other: Environmental, occupational and lifestyle-related exposures

Interventions

Environmental, occupational and lifestyle-related exposures OTHER

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

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Cases are defined as all 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. Two control subjects per case will be randomly selected from the French general population using electoral rolls and individually matched to case by age (by 5-year age group), sex and residential area.

You may qualify if:

• Cases
• Patients diagnosed in the previous 6 months from identification with a primary and histologically confirmed malignant sarcoma including soft-tissue, visceral and bone sarcomas as defined by the WHO classification of bones and soft tissue sarcoma, fourth edition, 2013;
• Living in the 15 districts participating to the study at the time of diagnosis
• French nationality (due to control selection within electoral lists);
• At least 18 years old at diagnosis;
• Agreed to participate to the study with a signed informed consent;
• Controls
• Subjects registered within the electoral rolls;
• At least 18 years old at interview;
• Living in the 15 districts participating to the study at the time of interview;
• Agreed to participate to the study with a signed informed consent;

You may not qualify if:

• Cases
• Patients with a known genetic predisposition to sarcoma such as Li-Fraumeni syndrome, Retinoblastoma syndrome, neurofibromatosis;
• Kaposi's' sarcoma;
• Protected adults' patients (aged of at least 18 years old) under guardianship by court order.
• Controls
• Subject previously diagnosed with a primary and histologically confirmed malignant sarcoma including soft-tissue, visceral and bone sarcomas as defined by the WHO classification of bones and soft tissue sarcoma, fourth edition, 2013;
• Protected adults' patients (aged of at least 18 years old) under guardianship by court order.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (10)

CHRU

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Oscar Lambret

Lille, France

Location

CHU Dupuytren

Limoges, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut régional du Cancer Montpellier

Montpellier, France

Location

CHU

Nantes, France

Location

CHRU

Strasbourg, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (35)

• Alexandrov LB, Stratton MR. Mutational signatures: the patterns of somatic mutations hidden in cancer genomes. Curr Opin Genet Dev. 2014 Feb;24(100):52-60. doi: 10.1016/j.gde.2013.11.014. Epub 2013 Dec 29.

  PMID: 24657537 BACKGROUND

• Bisanti L, Maggini M, Raschetti R, Alegiani SS, Ippolito FM, Caffari B, Segnan N, Ponti A. Cancer mortality in ethylene oxide workers. Br J Ind Med. 1993 Apr;50(4):317-24. doi: 10.1136/oem.50.4.317.

  PMID: 8494771 BACKGROUND

• Blair A, Zahm SH. Agricultural exposures and cancer. Environ Health Perspect. 1995 Nov;103 Suppl 8(Suppl 8):205-8. doi: 10.1289/ehp.95103s8205.

  PMID: 8741784 BACKGROUND

• Briggs NC, Levine RS, Hall HI, Cosby O, Brann EA, Hennekens CH. Occupational risk factors for selected cancers among African American and White men in the United States. Am J Public Health. 2003 Oct;93(10):1748-52. doi: 10.2105/ajph.93.10.1748.

  PMID: 14534232 BACKGROUND

• Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of sarcoma. Clin Sarcoma Res. 2012 Oct 4;2(1):14. doi: 10.1186/2045-3329-2-14.

  PMID: 23036164 BACKGROUND

• Downs TD, Crane MM, Kim KW. Mortality among workers at a butadiene facility. Am J Ind Med. 1987;12(3):311-29. doi: 10.1002/ajim.4700120307.

  PMID: 3674024 BACKGROUND

• Ducimetiere F, Lurkin A, Ranchere-Vince D, Decouvelaere AV, Peoc'h M, Istier L, Chalabreysse P, Muller C, Alberti L, Bringuier PP, Scoazec JY, Schott AM, Bergeron C, Cellier D, Blay JY, Ray-Coquard I. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One. 2011;6(8):e20294. doi: 10.1371/journal.pone.0020294. Epub 2011 Aug 3.

  PMID: 21826194 BACKGROUND

• Ducimetiere F, Lurkin A, Ranchere-Vince D, Decouvelaere AV, Isaac S, Claret-Tournier C, Suignard Y, Salameire D, Cellier D, Alberti L, Bringuier PP, Blay JY, Ray-Coquard I. [Incidence rate, epidemiology of sarcoma and molecular biology. Preliminary results from EMS study in the Rhone-Alpes region]. Bull Cancer. 2010 Jun;97(6):629-41. doi: 10.1684/bdc.2010.1117. French.

  PMID: 20504759 BACKGROUND

• Eriksson M, Hardell L, Adami HO. Exposure to dioxins as a risk factor for soft tissue sarcoma: a population-based case-control study. J Natl Cancer Inst. 1990 Mar 21;82(6):486-90. doi: 10.1093/jnci/82.6.486.

  PMID: 2313720 BACKGROUND

• Grimalt JO, Sunyer J, Moreno V, Amaral OC, Sala M, Rosell A, Anto JM, Albaiges J. Risk excess of soft-tissue sarcoma and thyroid cancer in a community exposed to airborne organochlorinated compound mixtures with a high hexachlorobenzene content. Int J Cancer. 1994 Jan 15;56(2):200-3. doi: 10.1002/ijc.2910560209.

  PMID: 8314301 BACKGROUND

• Guillou L, Aurias A. Soft tissue sarcomas with complex genomic profiles. Virchows Arch. 2010 Feb;456(2):201-17. doi: 10.1007/s00428-009-0853-4.

  PMID: 20217954 BACKGROUND

• Hardell L, Eriksson M. The association between soft tissue sarcomas and exposure to phenoxyacetic acids. A new case-referent study. Cancer. 1988 Aug 1;62(3):652-6. doi: 10.1002/1097-0142(19880801)62:33.0.co;2-4.

  PMID: 3390800 BACKGROUND

• Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF Jr. Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA. 1986 Sep 5;256(9):1141-7.

  PMID: 3801091 BACKGROUND

• Hoar Zahm S, Blair A, Holmes FF, Boysen CD, Robel RJ. A case-referent study of soft-tissue sarcoma and Hodgkin's disease. Farming and insecticide use. Scand J Work Environ Health. 1988 Aug;14(4):224-30. doi: 10.5271/sjweh.1928.

  PMID: 3175554 BACKGROUND

• Hoppin JA, Tolbert PE, Flanders WD, Zhang RH, Daniels DS, Ragsdale BD, Brann EA. Occupational risk factors for sarcoma subtypes. Epidemiology. 1999 May;10(3):300-6.

  PMID: 10230842 BACKGROUND

• Hossain A, McDuffie HH, Bickis MG, Pahwa P; Cross Canada Study of Pesticides and Health Researchers. Case-control study on occupational risk factors for soft-tissue sarcoma. J Occup Environ Med. 2007 Dec;49(12):1386-93. doi: 10.1097/JOM.0b013e318157d2f2.

  PMID: 18231085 BACKGROUND

• Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, Feigal EG, Edwards BK. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst. 2001 Jun 6;93(11):824-42. doi: 10.1093/jnci/93.11.824.

  PMID: 11390532 BACKGROUND

• IARC (2012). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 100. A review of human carcinogens, part D: radiation. Lyon, IARC (International Agency for Research on Cancer)

  BACKGROUND

• IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Chemical agents and related occupations. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt F):9-562. No abstract available.

  PMID: 23189753 BACKGROUND

• Karanian M, Coindre JM. [Fourth edition of WHO classification tumours of soft tissue]. Ann Pathol. 2015 Jan;35(1):71-85. doi: 10.1016/j.annpat.2014.11.003. Epub 2014 Dec 17. French.

  PMID: 25532684 BACKGROUND

• Kogevinas M, Kauppinen T, Winkelmann R, Becher H, Bertazzi PA, Bueno-de-Mesquita HB, Coggon D, Green L, Johnson E, Littorin M, et al. Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies. Epidemiology. 1995 Jul;6(4):396-402.

  PMID: 7548348 BACKGROUND

• Landrigan PJ. Critical assessment of epidemiologic studies on the human carcinogenicity of 1,3-butadiene. Environ Health Perspect. 1990 Jun;86:143-7. doi: 10.1289/ehp.9086143.

  PMID: 2205484 BACKGROUND

• Lurkin A, Ducimetiere F, Vince DR, Decouvelaere AV, Cellier D, Gilly FN, Salameire D, Biron P, de Laroche G, Blay JY, Ray-Coquard I. Epidemiological evaluation of concordance between initial diagnosis and central pathology review in a comprehensive and prospective series of sarcoma patients in the Rhone-Alpes region. BMC Cancer. 2010 Apr 19;10:150. doi: 10.1186/1471-2407-10-150.

  PMID: 20403160 BACKGROUND

• Mathoulin-Pelissier S, Chevreau C, Bellera C, Bauvin E, Saves M, Grosclaude P, Albert S, Goddard J, Le Guellec S, Delannes M, Bui BN, Mendiboure J, Stoeckle E, Coindre JM, Kantor G, Kind M, Cowppli-Bony A, Hoppe S, Italiano A. Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study. Ann Oncol. 2014 Jan;25(1):225-31. doi: 10.1093/annonc/mdt407. Epub 2013 Nov 26.

  PMID: 24285018 BACKGROUND

• Merletti F, Richiardi L, Bertoni F, Ahrens W, Buemi A, Costa-Santos C, Eriksson M, Guenel P, Kaerlev L, Jockel KH, Llopis-Gonzalez A, Merler E, Miranda A, Morales-Suarez-Varela MM, Olsson H, Fletcher T, Olsen J. Occupational factors and risk of adult bone sarcomas: a multicentric case-control study in Europe. Int J Cancer. 2006 Feb 1;118(3):721-7. doi: 10.1002/ijc.21388.

  PMID: 16108052 BACKGROUND

• Pahwa P, McDuffie HH, Dosman JA, Robson D, McLaughlin JR, Spinelli JJ, Fincham S. Exposure to animals and selected risk factors among Canadian farm residents with Hodgkin's disease, multiple myeloma, or soft tissue sarcoma. J Occup Environ Med. 2003 Aug;45(8):857-68. doi: 10.1097/01.jom.0000083033.56116.c1.

  PMID: 12915787 BACKGROUND

• Ray-Coquard I, Montesco MC, Coindre JM, Dei Tos AP, Lurkin A, Ranchere-Vince D, Vecchiato A, Decouvelaere AV, Mathoulin-Pelissier S, Albert S, Cousin P, Cellier D, Toffolatti L, Rossi CR, Blay JY. Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions. Ann Oncol. 2012 Sep;23(9):2442-2449. doi: 10.1093/annonc/mdr610. Epub 2012 Feb 13.

  PMID: 22331640 BACKGROUND

• Sathiakumar N, Delzell E, Austin H, Cole P. A follow-up study of agricultural chemical production workers. Am J Ind Med. 1992;21(3):321-30. doi: 10.1002/ajim.4700210305.

  PMID: 1585943 BACKGROUND

• Savage SA, Mirabello L, Wang Z, Gastier-Foster JM, Gorlick R, Khanna C, Flanagan AM, Tirabosco R, Andrulis IL, Wunder JS, Gokgoz N, Patino-Garcia A, Sierrasesumaga L, Lecanda F, Kurucu N, Ilhan IE, Sari N, Serra M, Hattinger C, Picci P, Spector LG, Barkauskas DA, Marina N, de Toledo SR, Petrilli AS, Amary MF, Halai D, Thomas DM, Douglass C, Meltzer PS, Jacobs K, Chung CC, Berndt SI, Purdue MP, Caporaso NE, Tucker M, Rothman N, Landi MT, Silverman DT, Kraft P, Hunter DJ, Malats N, Kogevinas M, Wacholder S, Troisi R, Helman L, Fraumeni JF Jr, Yeager M, Hoover RN, Chanock SJ. Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nat Genet. 2013 Jul;45(7):799-803. doi: 10.1038/ng.2645. Epub 2013 Jun 2.

  PMID: 23727862 BACKGROUND

• Smith JG, Christophers AJ. Phenoxy herbicides and chlorophenols: a case control study on soft tissue sarcoma and malignant lymphoma. Br J Cancer. 1992 Mar;65(3):442-8. doi: 10.1038/bjc.1992.90.

  PMID: 1558802 BACKGROUND

• Toro JR, Travis LB, Wu HJ, Zhu K, Fletcher CD, Devesa SS. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: An analysis of 26,758 cases. Int J Cancer. 2006 Dec 15;119(12):2922-30. doi: 10.1002/ijc.22239.

  PMID: 17013893 BACKGROUND

• Wibmer C, Leithner A, Zielonke N, Sperl M, Windhager R. Increasing incidence rates of soft tissue sarcomas? A population-based epidemiologic study and literature review. Ann Oncol. 2010 May;21(5):1106-11. doi: 10.1093/annonc/mdp415. Epub 2009 Oct 25.

  PMID: 19858086 BACKGROUND

• Wingren G, Fredrikson M, Brage HN, Nordenskjold B, Axelson O. Soft tissue sarcoma and occupational exposures. Cancer. 1990 Aug 15;66(4):806-11. doi: 10.1002/1097-0142(19900815)66:43.0.co;2-u.

  PMID: 2386907 BACKGROUND

• Woods JS, Polissar L, Severson RK, Heuser LS, Kulander BG. Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington. J Natl Cancer Inst. 1987 May;78(5):899-910.

  PMID: 3471999 BACKGROUND

• Lacourt A, Amadeo B, Gramond C, Marrer E, Plouvier S, Baldi I, Blay JY, Coindre JM, de Pinieux G, Gouin F, Italiano A, Le Cesne A, Le Loarer F, Monnereau A, Pellegrin I, Penel N, Ray-Coquard I, Toulmonde M, Ducimetiere F, Mathoulin-Pelissier S; Etiosarc study group. ETIOSARC study : environmental aetiology of sarcomas from a French prospective multicentric population-based case-control study-study protocol. BMJ Open. 2019 Jun 18;9(6):e030013. doi: 10.1136/bmjopen-2019-030013.

  PMID: 31217320 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Sarcoma

Interventions

Environment

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health

Study Officials

• Aude Lacourt, PhD

  French National Institute of Health and Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 14, 2018
• Study Start: April 25, 2019
• Primary Completion: July 3, 2024
• Study Completion: July 3, 2024
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available at any time
• Access Criteria: Data access requests will be reviewed by the steering committee Requestors will be required to sign a Data Access Agreement

Locations

FR (10)