The incidence of testicular cancer has increased in recent decades: In the past five decades, the incidence has more than doubled. This increase in occurrence suggests that the environment plays an important role in testicular cancer development; while a person’s genetic makeup undoubtedly plays a role, genetics alone would not account for these recent increases.
The study on the leather tanners suggests a role for environmental factors such as chemical pollutants, but many questions persist. If environmental factors play a role in testicular cancer, what other environmental factors might be involved? Can radiation play a role? Can particular microorganisms infect a person and contribute, directly or indirectly, to development of this cancer? Since testicular cancer typically develops early in life, can the intrauterine environment to which the developing fetus is exposed (e.g., toxicants, normal maternal chemicals such as hormones) play a role? Can a person’s own hormonal environment influence testicular cancer development? To what extent is a person’s hormonal environment influenced by factors in the external environment? Researchers continue to examine testicular cancer data in an attempt to identify relevant environmental factors for testicular cancer development. The task is challenging for many reasons, which include the small size of the pool of affected individuals, the fact that testicular cancer is not a single disease, and that analysis typically begins only after a diagnosis of testicular cancer has been made.
Studies have attempted to uncover links between testicular cancer and other factors, such as maternal age, but without success. An intriguing question arose about diethylstilbestrol (DES), a synthetic estrogen prescribed to many pregnant women between the late 1930s and early 1970s to prevent miscarriage. Sons of women who took DES during pregnancy could be at greater risk for testicular cancer. Many different investigations looked into this question. While it has been shown that DES daughters are at increased risk of a type of vaginal/cervical cancer and reproductive abnormalities, the only clearly demonstrated effect on DES sons is an increased risk for epididymal cysts, which are benign. It has not been established that DES sons are at increased risk of testicular cancer; some studies have shown that DES sons are at increased risk, while others have not shown a DES-testicular cancer relationship.
Katherine McGlynn and colleagues at the NCI have recently found evidence of a link between DDT, a pesticide now banned in the United States, and testicular GCTs. Their study took advantage of the fact that hundreds of U.S. servicemen had given blood samples well before any of them developed testicular cancer. These blood samples were still available and could be evaluated to see if any chemicals in them might be linked to later development of testicular cancer. The researchers found that those who had high concentrations of a DDT breakdown product in their blood were significantly more likely to eventually develop testicular cancer than those with low concentrations. DDT and other organochlorine (organic compounds with chlorine) pesticides have long been suspected in testicular cancer because they can affect hormones in the body, which themselves have been suspected to influence the risk of this cancer.
Testicular cancer risks and causes
Another way to assess environmental factors is to examine occupational risk-whether certain occupations (such as leather tanning) carry increased testicular cancer risk. For example, many studies show that firefighters are at increased risk for testicular cancers due to their occupational exposure to soot and chemicals such as benzene. (British Columbia now defines testicular cancer as an occupational risk for firefighters. ) Anothe r stud y suggeste d tha t th e us e o f handhel d radar guns by police (often positioned near testicles) might increase testicular cancer risk. Many other occupations have also been evaluated.
What is the role of genetics? A known, established risk factor for testicular cancer is a family history of testicular cancer. The greatest risk is having a brother with testicular cancer, which increases the risk up to tenfold, more than is normally seen with other cancers. This suggests an important role for genetics in the development of testicular cancer. (It is important to remember, however, that brothers often have numerous environmental factors in common.) If a gene or genes play a role, on what chromosomes are these susceptibility genes located?
Studies to find regions of chromosomes that may affect testicular cancer risk rely on analysis of affected families, defined as families with two or more individuals with testicular cancer. For testicular cancer, such studies are limited by the small number of affected families. To date, no studies have conclusively pointed to a specific chromosome region as associated with testicular cancer development. More likely, testicular cancer risk is influenced by many genes scattered throughout a person’s chromosomes.
If scientists do eventually find genes associated with testicular cancer, this will not rule out a role for the environment. Most likely, testicular cancer will be found to be caused by a combination of environmental and genetic factors.
Kathleen M. Verville, Ph.D.
Donna Bozzone, Ph.D.,
Professor of Biology
Saint Michael’s College
1. Centers for Disease Control and Prevention, “Epidemiologic and Reports Testicular Cancer in Leather Workers-Fulton County, New York,” Morbidity and Mortality Weekly Report 38, 7 (1989): 111-114.
2. S. M. Levin, D. B. Baker, P. J. Landrigan, S. V. Monaghan, E. Frumin, M. Braithwaite, and W. Towne, “Testicular Cancer in Leather Tanners Exposed to Dimethylformamide (letter),” Lancet 2, 8568 (1987): 1153.
3. A. Petterson, L. Richiardi, A. Nordenskjold, M. Kaijser, and O. Akre, “Age of Surgery for Undescended Testis and Risk of Testicular Cancer,” The New England Journal of Medicine 356, 18 (2007): 1835-1841.
4. C. Myrup, et al., “Correction of Cryptorchidism and Testicular Cancer (correspondence),” The New England Journal of Medicine 357 (2007): 825-827.