Authors
Ohlson, CG., Hardell, L.

Title
Testicular Cancer and Occupational Exposures with a Focus on Xenoestrogens in Polyvinyl Chloride Plastics.

Journal
Chemosphere, 40: 1277-1282 (2000)

Summary
The only well established risk factor for testicular cancer is cryptorchidism (undescended testes). Other hypotheses have speculated that prenatal factors play a role in the pathogenesis of the disease and recently, attention has been given to the influence of estrogenic chemicals on the pathogenic process of testicular cancer. Although controversial, estrogenic chemicals have also been implicated with other male reproductive disorders such as the rising incidence of hypospadias and cryptorchidism and declining sperm counts in men. This paper contributes to our understanding of the linkage between exposure to hormonally active environmental toxicants and testicular cancer because the association between exposure to polyvinyl chloride (PVC) and testicular cancer was investigated in a well designed and statistically robust study.

PVC contains several oestrogenic chemicals. Phthalates are used extensively in PVC as plasticizer of which over 30 different phthalates have been tested for their oestrogenic properties. Additionally, the additives bisphenol A and nonylphenol, that are known xenoestrogens, are used in plastics as antioxidants.

Ohlson et al. conducted a case-control study that investigated occupational exposures and testicular cancer. Testicular cancer cases were men between the ages of 30 and 75 who reported to the Swedish Cancer Registry between 1989 and 1992. There were a total of 163 cases, 109 cases of with seminoma testis and 54 cases with embryonal cancer. The Swedish Population Registry was used to sample 363 controls by selecting the next subject in the birth registration number. Therefore, the cases and controls were born in the same year. No further matching of the cases and controls was done. A 22-page mail out questionnaire was distributed to collect information on lifetime work history & specific exposures. The questionnaires were reviewed by a trained nurse and supplemented by a blinded phone interview if necessary. The results of this study demonstrated that plastic workers were at increased risk for testicular cancer (OR= 2.9, CI=1.3-1.6). Exposure specifically to PVC was found to significantly increase the risk of testicular cancers (OR=6.6, CI=1.4 - 32). Furthermore, if those subjects who had cryptorchidism were removed from the analysis, the OR increased to 14 (CI=1.7-114) for all testicular cancer. As well, when the orchitis case were removed the OR was 10.0 (CI=1.2-87). When dividing the exposed group into lowest verses highest cumulative exposures there appeared to be a dose-response relationship for PVC. Six of the seven exposed cases had seminoma and those with embryonal cancer had a low cumulative exposure. Seminoma occurs in older age than embryonal which the authors suggest increase the probability of an occupational association. Other types of plastics did not have significantly increased risks for testicular cancer or dose-response relationships. Other analyses showed that exposure to transformer oil and insect repellent was more frequent among cases (all seminoma) then among controls.

Ohlson et al. put forward several issues in the interpretation of their results. Firstly, the complex interplay between xenoestrogens, their metabolites, 17-ß-oestradiol, oestrogen receptors and tumor induced testis cells is not clear. Secondly, although these chemicals have proven oestrogenic potencies they are much less potent than the natural hormone 17-ß-oestradiol. Finally, there may be different mechanisms at play regarding the two types of testicular cancers. Embryonal cancer occurs mainly in younger men and is influenced by hormonal factors in early infancy while the incidence of seminoma peaks in older age, indicating a possible role of occupational exposures. This study has several important limitations; direct measures of contaminant exposure were not made, and because it is retrospective study the outcome is dependant on subject recall and self-administered questionnaires which are notoriously poor. Regardless, the results of this study are instructive and useful for hypothesis generating and to guide future research.