1. Froelich, Warren

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Adolescent Latino boys in California exposed in utero to a commonly used pesticide spread in fields near their mothers' homes are at an increased risk of developing testicular germ cell cancer (TGCT), according to a study presented at a virtual meeting on cancer health disparities held October 2-4, 2020, by the American Association for Cancer Research (AACR).

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The study found that residential proximity to the application of acephate, an endocrine disrupting pesticide (EDP), in the year before birth may have contributed as much as 10 percent to the prevalence of TGCT among Latinos in California. TGCT, which has been steadily rising since the mid-20th century, particularly among Latinos, is the most predominant form of testicular cancer.


"The core takeaway is that certain commonly used pesticides-acephate, in particular-can increase a patient's risk of developing testicular cancer when applied near their home while in the womb, and that this connection between acephate application and testicular cancer was particularly strong among Latinos," said Scott J. Swartz, an MD candidate in the University of California Berkeley-UCSF Joint Medical Program who presented the results at AACR.


"This suggests that increasing EDP application and exposure could be a possible driver of the increasing testicular cancer rates we've seen in recent decades," Swartz added.


Interestingly, the study assessed a total of 22 EDPs, but only acephate was associated with an increased risk for TGCT. Acephate is an organophosphate insecticide used on food crops and citrus trees, as a seed treatment, on golf courses, and in commercial or institutional facilities. People can be exposed to acephate by breathing in the spray mist or by getting spray or granules on their skin.


"Most pesticides we looked at did not show a strong correlation to testicular cancer, though a few did," Swartz said. "Acephate showed the strongest and most consistent connection, especially among Latinos."


TGCT is the most frequently occurring cancer among young men ages 15-44 years in the United States. Incidences of TGCT have steadily risen among Latinos in recent decades, with a 2.3 percent increase in annual cases compared to a .5 annual increase among non-Latinos whites.


According to one study published in 2017 in the journal Cancer, between 2013 and 2026, rates among Hispanics were forecast to increase by 3.96 percent annually, the highest rate of increase of any racial/ethnic group (2017; doi: 10.1002/cncr.30597). By 2026, the highest TGCT rates in the U.S. will be among Hispanics. Rates among non-Hispanic whites will increase slightly, while rates among other groups will decrease slightly.


Research also has traced TGCT to fetal origins, with endocrine disruption in utero suspected of playing a key role in its pathogenesis.


Study Details

For this study, Swartz and colleagues compiled a list of California's historic pesticide application for 22 EDPs from the California's Pesticide Use Reporting (PUR) database, in addition to the home addresses at birth of people who did and did not go on to develop testicular cancer.


The case-control study included 381 patients-336 nonseminomas and 44 seminomas-diagnosed with TGCT between the ages of 15 and 19 years from 1997 to 2011, obtained from the California Cancer Registry. Nonseminomas and seminomas represent the two basic types of testicular cancer. Results were compared to 762 otherwise healthy controls matched for birth year and race/ethnicity.


The statistical analysis included 15 high-volume EDPs to which 50 or more participants were exposed, accounting for the timing of pesticide application, histologic subtype, race/ethnicity, birth year, and neighborhood socioeconomic status.


As outlined in Swartz's presentation, some 48 percent of cases and 45 percent of controls lived within a 3 km radius of an EDP application in the year before birth. Nearby pesticide applications were greater among Latinos than non-Latinos for 13 of 15 EDPs; the median for total EDP application was 29 kg (5-135) for Latinos versus 11 kg (1-80) for non-Latinos.


Pesticide applications were also greater for 14 of 15 EDPs for those born after 1990-the period of time with complete PUR reporting-than before 1990.


The results showed an increased risk of TGCT associated with acephate (OR: 1.1, 95%, CI, 1-1.2) and (OR 1.3, 95% CI, 1-1.7) for continuous or low doses over a long period of time, and binary (acephate plus another pesticide) exposures, respectively.


When stratified for ethnicity, risk remained elevated for acephate application among 614 Latino participants (OR for continuous exposure model = 1.1; 95% CI, 1-1.2) and 504 non-Latino participants for pesticides containing carbonyl (OR=1.2; 95% Cim 1-13) and copper sulfate (OR=1.1, 95% CI, 1-1.3).


All other EDPs analyzed in the study had null results in all categories. Attributable risk was also calculated using a no-or-low versus high nearby EDP application rather than a continuous exposure.


"Acephate in the post 1990-only subgroup showed an especially high population attributable risk percentage of about 10.2," said Swartz.


Any reason why acephate appeared to be riskier than other EDPs mentioned in the study? Swartz said many studies in rats and mice models, and one in human sperm cells, demonstrate that acephate disrupts male reproductive system development and function.


"However, similar results have been published for many of the pesticides we investigated in this study (which is, after all, why they were classified as endocrine disrupters in the first place)," he said. "Beyond biochemical mechanisms, it is also possible that there is something peculiar about acephate's distribution in the environment that could set it apart from other endocrine-disrupting pesticides risk wide."


Swartz noted their retrospective study, the first of its kind to assess geospatial proximity to EDPs and TGCT risk, especially among Latinos, had some limitations.


"Limitations include the fact that application doesn't necessarily equal exposure," he said. "There may have been under-reporting prior to 1990, which might bias our result toward the null. EDP combination effects were not assessed."


As for next steps, Swartz said he hoped other studies, particularly prospective studies, would focus on testicular cancer's relationship to exposure to EDPs, so the latter can be assessed more accurately.


"Also, specifically, acephate's effects on reproductive health should be investigated more thoroughly in both humans and animals," he concluded.


Warren Froelich is a contributing writer.