Testicular cancer is a relatively uncommon malignancy where cells in one or both testicles grow abnormally. Understanding its risk factors is important for awareness and early detection, helping individuals and healthcare providers recognize potential risks and promote timely intervention.
Established Biological Factors
Cryptorchidism, an undescended testicle, is a recognized biological factor. Normally, testicles descend into the scrotum during fetal development. In about 3% of male infants, one or both do not fully descend, remaining in the abdomen or groin.
Boys with cryptorchidism have a four to six times higher risk of testicular cancer in the undescended testicle. Even after surgical correction (orchiopexy), the risk remains two to threefold higher than in individuals without cryptorchidism. This increased risk is thought to stem from an underlying abnormality in the testicle that also prevents proper descent.
A personal history of testicular cancer in one testicle elevates the risk of developing it in the other. About 3% to 4% of men successfully treated for cancer in one testicle will eventually develop it in the remaining testicle, a risk about 12 times greater than for men who have never had testicular cancer.
Carcinoma in Situ (CIS), or Germ Cell Neoplasia in Situ (GCNIS), is a significant precursor. This condition involves abnormal germ cells within the testicle’s seminiferous tubules that have not spread beyond the tubule walls. CIS is considered a direct precursor to invasive testicular cancer. If left untreated, there is a 50% chance of CIS progressing to invasive cancer within five years, and progression is believed to occur in all cases given sufficient time.
Genetic and Familial Predispositions
Family history can influence testicular cancer risk. Individuals with a close relative who has had the disease face an elevated risk, though about 90% of cases do not have a family history.
The risk is eight to twelve times higher if a brother has had testicular cancer, and two to four times higher if a father has had it. While no specific gene is definitively identified, the disease shows some heritability. Certain inherited conditions, such as Klinefelter syndrome, also increase risk.
Demographic and Lifestyle Factors
Age is a prominent demographic factor influencing testicular cancer risk. It is most frequently diagnosed in younger and middle-aged men, with an average age of 33. It is the most common malignancy among men aged 20 to 40. While it can occur at any age, about 6% of cases are found in children and teenagers, and 7% occur in men over 55.
Racial and ethnic disparities are observed in testicular cancer incidence. White men in the United States have a higher incidence rate, with a risk five to ten times greater than African American men and more than double that of Asian American men. Incidence among Hispanic or Latino men is increasing, with some projections suggesting they may have the highest rates in the U.S. by 2026. The precise reasons for these differences are not fully understood, but may involve socioeconomic factors, access to care, and biological variations.
The relationship between body size and testicular cancer is an area of ongoing research with mixed findings. Some studies suggest a lower risk among men with a higher Body Mass Index (BMI), while others report no significant association. Taller men have shown a positive association with testicular cancer risk, independent of BMI. The biological mechanisms underlying these observations are still being investigated.
Environmental and Other Factors
HIV infection is linked to an increased risk of testicular cancer, particularly seminoma. Men with HIV/AIDS have shown an elevated risk of seminoma, with some studies indicating a nearly twofold increase. This association is thought to be related to a weakened immune system, which may reduce the body’s ability to detect and eliminate cancerous cells.
Exposure to certain environmental chemicals, such as phthalates and pesticides, has been investigated as potential risk factors. Phthalates, found in plastics and personal care products, are endocrine-disrupting chemicals that can interfere with hormone action. Prenatal exposure to phthalates has been linked to testicular dysgenesis syndrome (TDS) in animal models, which includes testicular cancer, undescended testicles, and reduced sperm quality. Some studies suggest a connection between prenatal exposure to certain pesticides, such as acephate and malathion, and an increased risk of testicular germ cell tumors in adolescents. Research on occupational pesticide exposure has yielded conflicting results.
Radiation exposure is another environmental factor. While testicles are generally considered relatively insensitive to ionizing radiation, some studies suggest that early and repeated exposures to diagnostic imaging, such as X-rays and CT scans below the waist, may increase testicular cancer risk. This increased risk is thought to stem from radiation’s ability to damage DNA, potentially leading to cancer-causing genetic mutations. Studies on occupational radiation exposure have shown limited or inconsistent evidence for a direct association.