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

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 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;
  * Diagnosed over a three-year period with an inclusion start date ranging from the 1st October 2018 to the 1st January 2020;
  * 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;

Exclusion Criteria:

* 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.

• BACKGROUNDAlexandrov 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
• BACKGROUNDBisanti 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
• BACKGROUNDBlair 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
• BACKGROUNDBriggs 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
• BACKGROUNDBurningham 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
• BACKGROUNDDowns 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
• BACKGROUNDDucimetiere 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
• 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.