Fact Sheets

Testicular Cancer

Issue: The incidence of testicular cancer in western countries has increased steadily in the past 40-50 years. The etiology of testicular cancer is not well understood, but there is sufficient evidence to postulate a link with endocrine modulating substances.

Background: Testicular cancer is a rare cancer, with an age-adjusted incidence of 4.2/100,000 in Canada. This accounts for 1.1% of all malignant neoplasms in Canadian males. Despite the low overall incidence of testicular cancer, it is the most common malignancy among young men, 25-34 years old. Testicular cancer varies notably with race, with incidence rates about threefold higher in Caucasians compared to African Americans in the US.

Disease trends: The incidence rate of testicular cancer has been increasing since the middle of the 20th century in many western countries, including Canada, the United States, the Nordic Countries, and Britain. The trend has been especially rapid in eastern European countries such as Slovenia. Countries with a sufficiently long period of cancer registration, such as Denmark, document this trend back to the first half of the 20th century. Despite the increase in testicular cancer in many western countries, the age-adjusted incidence of testicular cancer is low in all populations of the world. The lowest rates have been observed in Asian populations, African Americans, and black populations in general. The incidence rate in Denmark is in the order of 8 per 100,000, while in Japan and China and in African Americans, the incidence rate is on the order of 1 per 100,000. While the increase in testicular cancer incidence is an important cause of morbidity in young males, testicular cancer is one of the most curable of all solid neoplasms. The five year survival rate has increased during the last 30 years from 63% to over 90%. The present case fatality rate is 10-15 percent, and even in metastatic cases, cure rates are as high as 80 percent.

Consistency of the data: The etiology of testicular cancer is poorly understood. Most of the established risk factors are related to in utero events including: cryptochidism or maldescendent testicles, carcinoma in situ and exposure to estrogen in utero. These established risk factors suggest that hormonal exposures may affect testicular cancer risk, particularly exposure to estrogen in utero. However, the exact nature of the link between estrogen exposure and testicular cancer is unclear. It has been suggested that exposure to high levels of estrogen in utero results in the development of carcinoma in situ, which appears to be a precursor of testicular cancer. The associations between estrogen exposure and testicular cancer include an increased risk associated with: nausea in pregnancy resulting from high endogenous estrogen levels, DES exposure, and non-specified hormone use in pregnancy. In addition to these exposures, endogenous maternal estrogen levels are higher in first pregnancies as compared to subsequent ones and several studies have found that children of mothers with high parity have a decreased risk of testicular cancer when compared to male children of nulliparous mothers. Twin studies have observed that dizygotic twin pregnancies have higher maternal hormones levels than monozygotic pregnancies. As a result, dizygotic twins have a higher risk of testicular cancer than monozygotic twins. Finally, maternal smoking may be protective of testicular cancer, possibly be due to increased turnover of estrogen in cigarette smokers. It would appear that estrogen has an important role in the etiology of testicular cancer, and warrants further study.

Testicular germ cell tumors in adults are a well described cytogenetic entity. They have a chromosome number in the triploid range, and are characterized by specific chromosomal gains at chromosomes 7, 8, 12, 21, and X, and by specific chromosomal losses at chromosomes 11, 13, and 18. A non-random genetic alteration has been localized to i(12p). Studies have shown that 80% of testicular tumors have one or more copies of i(12). It would seem that isochromosome 12p is the recurrent structural chromosomal abnormality of these tumors. It has been estimated that 33.4% of all cases of testicular cancer are in individuals with the malignant genotype, assuming it is a recessive trait.

Other risk factors of testicular cancer that have been examined include: occupation, chemical exposure, radiation exposure, socio-economic status, and diet. Recent studies regarding testicular cancer risk and diet have pointed to a risk associated with dairy products. In addition to fats, protein and calcium, milk and dairy products contain considerable amounts of female sex hormones such as estrogens and progesterone. These hormones are a result of the fact that present-day milk is produced from pregnant cows. A significant elevated risk of testicular cancer has been linked to exposure to polyvinyl chloride; however this has yet to be confirmed.

Experimental evidence: The types of testicular cancer commonly found in humans are preceded by atypical intratubular germ cells termed CIS (carcinoma in situ) which is extremely rare in laboratory animals. Until recently, experimental animal models appropriate for extrapolation to humans were lacking. CIS like lesions have been induced in rabbits exposed in utero and/or in infancy to the toxicants octylphenol, p,p'- DDT/DDE or zeranol. These results illustrate the potential relevance of the rabbit as a model for this type of cancer in humans. However, validated animal models for germ cell (testicular) tumours observed in man currently do not exist.

Biological plausibility: Despite the absence of direct human evidence, the role of man-made chemicals can contribute to the pathogenesis of testicular cancer development by the estrogenetic/anti-androgenetic effect of the hormones on the testes. However, the hormonally active environmental chemicals involved, the pathways in which they act, and their associated risk of cancer remain unknown.

Conclusion: The etiology of testicular cancer remains unknown. However, many of the risk factors point towards a hormonal mechanism of carcinogenesis. Currently there is a lack of direct evidence regarding the link between environmental endocrine disrupting chemicals and testicular cancer risk. As well, the link between estrogenic or anti-androgenic compounds and testicular cancer has not yet been examined. In addition, the current lack of a suitable animal model prevents definitive conclusions on the role of hormonally active environmental chemicals on testicular cancer risk.