What causes testicular cancer?

Causes of Testicular Cancer

Testicular cancer is primarily caused by genetic predisposition, with environmental factors such as exposure to endocrine-disrupting chemicals playing a significant contributory role. 1

Genetic Factors

• Family history: Higher risk among brothers (relative risk 6.3) and sons/fathers (relative risk 4.4-4.7) of affected individuals 1
• Genetic polymorphisms: Multiple low-risk and moderate-risk single nucleotide polymorphisms account for approximately 37% of familial testicular germ cell tumor risk 1
• DNA repair genes: About 10% of testicular germ cell tumor cases have pathogenic germline DNA repair gene variants, with CHEK2 being a potential moderate-penetrance susceptibility gene 1
• Contralateral risk: Approximately 5% of men with testicular cancer develop contralateral testicular cancer, suggesting genetic predisposition 1

Environmental and Developmental Factors

• Testicular dysgenesis syndrome (TDS): A developmental disorder of the gonads caused by environmental and/or genetic influences early in pregnancy 1
• Endocrine-disrupting chemicals: Exposure to chemicals like organochlorine insecticides increases the risk of germ cell tumors 1
• Cryptorchidism (undescended testicles):
  • 3.6-7.4 times higher risk of developing testicular cancer 1
  • 2-6% of men with cryptorchidism history will develop testicular tumors 1
  • Early orchidopexy (before puberty) can reduce but not eliminate the risk 1

Other Risk Factors

• Age: Most common in men 15-40 years old, with mean age at diagnosis of 33 years 2
• Race/Ethnicity: Higher incidence in white men 2, 3
• Infertility: Associated with increased risk of testicular cancer 1, 2, 3
• Cannabis use: Identified as a potential risk factor 2
• Genetic conditions: Klinefelter syndrome and other disorders of gonadal development 2

Pathophysiology

• Origin: 90-95% of testicular cancers are germ cell tumors 2
• Development pathway: Invasive testicular cancer develops from carcinoma in situ (CIS)/testicular intraepithelial neoplasia (TIN), often found in residual non-malignant testicular tissue 1
• Contralateral risk: 2-5% of testicular cancer patients have carcinoma in situ in the contralateral testis 1

Clinical Implications

• Screening: Regular self-examination is crucial for those with risk factors 4
• Fertility preservation: Sperm banking should be discussed early due to high risk of infertility 4
• Long-term monitoring: Patients with risk factors (especially cryptorchidism) require vigilant monitoring due to increased cancer risk 1
• Contralateral testing: Consider biopsy of the contralateral testis in high-risk patients (history of cryptorchidism, testicular volume <12 ml, hypospermatogenesis) at the time of orchiectomy 1

Prevention Strategies

• Early orchidopexy: Treatment of cryptorchidism before puberty reduces but doesn't eliminate cancer risk 1
• Regular self-examination: Particularly important for those with risk factors 4
• Awareness of family history: Those with affected family members should be particularly vigilant about monitoring 1

Understanding these risk factors is crucial for early detection, as testicular cancer has excellent survival rates (97-99% five-year survival) when diagnosed early 2, 3.