Occupational exposure to organic solvents and the risk of developing testicular germ cell tumors (TESTIS study): Effect of combined exposure assessment on risk estimation

Objectives Etiological factors of testicular germ cell tumors (TGCT) remain largely unknown, but a causal role of occupational exposures to solvents has been suggested. Previous studies analyzing these exposures reported discordant results, potentially related to exposure assessment methods. The aim of this study was to investigate the role of occupational exposure to solvents on the risk of developing TGCT among young men. Methods This study examined occupational exposures to solvents and TGCT risk based on the lifetime work histories of 454 cases and 670 controls, aged 18–45 years, of the French national TESTIS case–control study. Solvent exposure was estimated using: (i) exposure assignment by job-exposure matrix (JEM) and (ii) JEM combined with self-reported exposure data from specific questionnaires (SQ) and expert assessment (EA). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Results Both approaches (JEM and JEM+SQ+EA) showed a consistent association between TGCT and trichloroethylene exposure (exposed versus not exposed; JEM=OR 1.80 [95% confidence interval (CI) 1.12–2.90] and JEM+SQ+EA= OR 2.59 (95% CI 1.42–4.72). Both approaches also observed positive associations with ketone esters and fuels & petroleum-based solvents. Conclusion The results suggest that some organic solvents might be involved in the pathogenesis of TGCT among occupationally exposed men. The combined use of JEM+SQ+EA seemed to limit misclassification by considering individual exposure variability and is, therefore, an appealing approach to assess occupational exposures in epidemiological studies.


High
Abbrevia�ons -OR: odds ra�o; 95% CI: confidence interval of 95%; Ca/Co (ever)/(never): a Es�mates obtained comparing TGCT cases to group A and group B controls combined and adjusted for sibship size, being born from mul�ple pregnancy, personal history of tes�cular trauma, family history of TGCT and family history of cryptorchidism.Analysis was restricted to subjects with no missing data for the adjustment variables (N=12).Results presented if a job was held by more than five cases and five controls.b 40 cases with personal history of cryptorchidism were excluded from the analyses.c 43 cases not confirmed by pathology reports, were excluded from the analyses..
Figure S1.Flow chart of the TESTIS study popula�on

Table S2 .
Example of changes over �me in exposure to trichloroethylene for the same job, in the Matgéné job exposure matrix

Table S3 .
Indices from JEMs for all solvents and weight values used for the cumulative exposure estimates calculations.

Table S4 . Combined approach combing JEM and SQ assessments with expert assessment: number
of jobs-periods concerned by each of the seven condi�ons and decision rules defined,TESTIS study,  2015TESTIS study,   -2018.   .
Abbrevia�ons -E: Exposed; Not E: Not Exposed; KetEst: Ketones and esters; Petroleum solvents: Fuels & Petroleum-based solvents; TCE: Trichloroethylene; PCE: Perchloroethylene; MC: Methylene chloride.2,540 job-periods were concordantly assessed as exposed or unexposed by the JEM and the SQ, and 1,273 jobs-periods with at least one discordant exposure assessment between JEM and SQ, i.e., assessed by the JEM as exposed [or not exposed] while assessed by the SQ as unexposed [or as exposed].

Table S6 .
Prevalence of occupa�onal exposure to organic solvents for cases and controls, TESTIS study,2015-2018.

Table S7 .
Sensibility analysis when "discordant" jobs evaluated by the JEM between 10 and 70% were classified as non-exposed, TESTIS study, 2015-2018.Es�mates obtained comparing TGCT cases to group A and group B controls combined and adjusted for sibship size, being born from mul�ple pregnancy, personal history of tes�cular trauma, family history of TGCT and family history of cryptorchidism.Analysis was restricted to subjects with no missing data for the adjustment variables (N=12).Results presented if a job was held by more than five cases and five controls. a

Table S8 .
Odds ra�os and 95% confidence intervals for TGCT associated with occupa�onal exposure to solvents ; use of the combined assessment method in sensi�vity analyses,TESTIS study, 2015TESTIS study,  -2018.   .

Table S9 .
Analysis for a "change in es�mate" adjustment method suggested byTalbot and Massamba, 2019 (Talbot & Massamba, 2019), example of results with individual exposure to TCE, TESTIS study.

Table S9
continued.Analysis for a "change in es�mate" adjustment method suggested byTalbot and Massamba, 2019 (Talbot & Massamba, 2019), example of results with individual exposure to TCE, TESTIS study.

Table S9
continued.Analysis for a "change in es�mate" adjustment method suggested byTalbot and Massamba, 2019 (Talbot & Massamba, 2019), example of results with individual exposure to TCE, TESTIS study.