Phthalates measured at birth and risk of testicular cancer in adolescents and young adults

Abstract Background The incidence rates of testicular germ cells tumors (TGCT) are increasing in adolescents and young adults in the United States, especially in Latinos. We investigated the association between TGCT risk and birth levels of phthalates, known endocrine disrupting chemicals, in a diverse population in California. Methods Reverse phase chromatography was applied to newborn blood samples of 196 TGCT cases and 190 controls to measure ten phthalates, five of which passed quality control: Mono-2-methyl-2-hydroxypropyl phthalate/mono-3-hydroxy butylphthalate (MHiBP/MHBP), Mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-oxo-isononyl) phthalate (MOiNP), and Mono(2-ethylhexyl) phthalate (MEHP). We conducted single chemical and mixture analyses using weighted quantile sum (WQS) regression, adjusting for birth and sociodemographic characteristics, and hematocrit. We ran repeated holdout analyses splitting data between training and testing sets 100 times. Results None of the single phthalates was significantly related to case status. The overall WQS analyses showed a curvilinear mixture effect related to TGCT risk, approximated with linear and quadratic terms, and dominated by MECPP and MEHP mostly in the lower concentration ranges. For Latinos, the curvilinear mixture effect was dominated by MEHP, and the WQS betas were borderline significant (median b1 = 0.37, 95%CI = -0.25, 1.28; median b1sq=-0.04, 95%CI = -0.15, 0.03), with high level of reproducibility for beta estimations in the repeated analyses (87% to 89%). For non-Latino whites, the mixture effect was dominated by MECPP and MHiBP/MHBP, although the signal for curvilinearity and repeated analyses were less robust. Conclusions Prenatal exposure to phthalate mixtures may increase TGCT risk later in life, with some variation by racial/ethnic group.