Authors
Hardell, L., van Bavel, B., Lindström, G.; Carlberg, M.; Dreifaldt, AC, Wijkström, H.; Starkhammer, H., Eriksson, M., Hallquist, A., Kolmert, T.

Title
Increased concentrations of polychlorinated biphenyls, hexachlorobenzene and chlordanes in mothers to men with testicular cancer.

Journal
Environmental Health Perspectives, in press

Summary
It has been hypothesized that an increase in prenatal estrogen exposure may adversely affect the development of the male reproductive tract. Testicular cancer arises from carcinoma in-situ (CIS) presumed to derive from germ cells that have escaped normal differentiation in utero. Undescended testes, the failure of one or both testes to descend into the scrotum at birth, are a known risk factor for testicular cancer. Animal studies have shown that high levels of estrogen during the first trimester of pregnancy increase the risk of testicular cancer and cryptorchidism. In light of this evidence, concerns have been raised regarding the effect of maternal levels of exogenous chemicals that exhibit estrogenic activity on the development of the male reproductive tract.

Experimental studies have shown that some persistent organic pollutants (POPs) have estrogenic properties. The objectives of this study were to investigate blood concentrations of specific POPs in men with testicular cancer and their mothers compared to a group of control men without testicular cancer and their mothers. Incident cases of testicular cancer between 1997 and 2000 from four hospitals in Sweden were included in this study with both patients and their mothers asked to give blood. All cases (n=58) agreed to participate. Twenty-two of the cases had seminomas, and 36 had non-seminomas (28 embryonal, 8 teratoma). The controls were drawn from the Swedish population registry. Each person in Sweden has a unique personal ID number in the national registry. Controls were randomly drawn from within 5-yr age strata. (mothers were to be within 5 years of case/control). The refusal rate was low (n=15) and in total there were 61 controls. Blood samples from both the cases and controls, and their respective mothers were analyzed for a variety of different persistent organic pollutants (POPs).

The results showed that the testicular cancer cases had an increased concentration of only one POP, cis-nonchlordane (OR=2.6 (1.2-5.7)). However, the mothers of the cases had an increased concentration PCBs (OR=3.8, CI=1.4-10), hexachlorobenzene (OR=4.4, CI=1.7-12), trans-nonachlordane (OR=4.1, CI=1.5-11), cis-nonachlordane (OR=3.1, CI=1.2=7.8) and cis-chlordane (OR=2.5, CI=0.99-6.1).

Results of this study suggest that the mothers of Swedish men with testicular cancer had higher levels of specific POPs measured three decades after the hypothesized critical window of exposure thought to be important in the causal pathway for the development of testicular cancer. The fact that the blood levels were taken several years after the men were exposed in utero is a major drawback to the study. The median time from the fetal period until the blood sampling was 30 years for cases and 31 years for controls. The authors tried to control for this limitation by matching the case and control mothers by age. As well, adjustments were made for lactation, and body mass index which are known to influence contaminant levels in women. However, within that time period it is possible that there were individual differences in exposure and metabolism patterns amongst the women. Estimates suggest that the half-life of PCBs ranges from 7-30 years and thus, the differences in exposure seen in this study may reflect differences in exposure when the women were pregnant. Additional investigation is required.