DDT EXPOSURE LINKED TO TESTICULAR CANCER

August 20, 2010 — In utero exposure to the pesticide DDT (dichlorodiphenyltrichloroethane), which is an endocrine-disrupting chemical, might increase the risk of developing testicular cancer, according to a new study published in the July–September issue of the Archives of Environmental & Occupational Health.

Barbara Cohn, PhD, and colleagues from the Child Health and Development Studies (CHDS) in Berkeley, California, found that maternal serum levels of DDT-related compounds, which were measured in the early postpartum period, were associated with the offspring's risk for testicular cancer.

The rate of testicular germ cell tumors has been increasing for several decades, and this study adds to evidence of an environmental link, note the authors.

"This study is unique and valuable [in that it is the first to] provide information about prenatal and early postnatal exposure in testicular cancer cases," said Shanna Swan, PhD, professor of obstetrics and gynecology, and of environmental medicine at the University of Rochester Medical Center in New York, in a statement.

Dr. Swan, who was not involved in the study, is an expert on environmental chemicals and male reproduction. She points out that the study was " based on blood samples from a median of 30 years prior to diagnosis, and I don't know of another study that has that capability."

Lends Strength to Previous Research

Previous studies have reported links between endocrine-disrupting chemicals, such as organochlorinated pesticides like DDT, and testicular cancer. In 2008, researchers found that increased exposure to p,p'-DDE (1,1,1-trichloro-2,2-bis[p-chlorophenyl]ethane) was associated with the risk for both seminomatous and nonseminomatous testicular germ cell tumors, and that chlordane isomers are associated with the risk for seminoma (J Natl Cancer Inst. 2008;100:663-671).

As reported by Medscape Medical News, an increased incidence of congenital anomalies, including cryptorchidism and hypospadias, has been reported in boys whose mothers had higher serum levels of certain organohalogen compounds.

DDT Compounds Used to Determine Exposure

In their study, Dr. Cohn and colleagues note that the incidence of testicular cancer has risen dramatically since 1945, the same year that the commercial use of DDT was introduced worldwide. Commercial-grade DDT is one of the most ubiquitous exposures in history, they write. Nearly all blood and tissue samples obtained in the United States from the 1960s to the 1980s had measurable levels of DDT-related compounds, complicating studies on exposure.

"Thus, the analytic strategy for studying DDT exposure in relation to human health is not simple; it is not possible to compare the exposed with the unexposed," they write. "Instead, simultaneous consideration of several DDT-related compounds can be informative in devising a measure of exposure."

The relevant DDT compounds are p,p'-DDT, which is the primary component and active ingredient of commercial DDT; o,p'-DDT (1,1,1-trichloro-2-[p-chlorophenyl]-2-[o-chlorophenyl]-ethane), which is a low-level contaminant of commercial DDT; and p,p'-DDE (1,1'-dichloro-2,2'-bis[p-chlorophenyl]ethylene), which is the primary metabolite of p,p'-DDT.

Of these compounds, o,p'-DDT is the least persistent and a marker of recent exposure to commercial-grade DDT. Conversely, p,p'-DDE is the most persistent, and a potent antiandrogenic DDT metabolite.

The study was based on data drawn from the CHDS's 40-year follow-up of 20,530 Northern California pregnancies that occurred between 1959 and 1967. The authors chose to use the p,p'-DDT/p,p'-DDE (DDT/DDE) ratio in maternal serum as an indicator of exposure source and timing. Because a higher DDT/DDE ratio could be caused by either slower elimination of p,p'-DDT or more recent exposure to commercial DDT, they also evaluated maternal o,p'-DDT as an additional indicator of recent exposure.

They found that of the 9744 sons born alive during the study period, 15 were diagnosed with germ cell testicular cancer and had maternal serum samples. These 15 cases were matched to 3 control subjects.

Overall, the gestational period was significantly shorter for testicular cancer cases, and the mothers had lower levels of p,p'-DDT, o,p'-DDT, and p,p'-DDE, but a higher DDT/DDE ratio, than the control subjects. The higher DDT/DDE ratio observed in mothers of cases is consistent with more recent exposure to commercial DDT or slower elimination of p,p'-DDT, note the authors.

"The associations we observed in this study are of considerable interest given the low statistical power of this study, and the lack of other strong risk factors for testicular cancer identified to date," they conclude. "A better understanding of individual differences in DDT metabolism and the relationship of DDT to the induction of enzymes that metabolize other endogenous and exogenous exposures will be important for full interpretation of our findings."

The study was funded by the Lance Armstrong Foundation and the National Institutes of Health. The authors have disclosed no relevant financial relationships.

Arch Environ Occup Health. 2010;65:127-134. Abstract