Testicular cancer (TC) is a relatively uncommon malignancy, yet it is the most frequently diagnosed cancer among men aged 15 to 35. While the exact biological cause remains unconfirmed, researchers have identified several strong non-modifiable risk factors that significantly increase susceptibility. Understanding these established associations is necessary for early detection and guiding ongoing research.
Established Biological Risk Factors
The most significant and well-documented risk factor is cryptorchidism, a condition where one or both testicles fail to descend fully into the scrotum before birth. This process is incomplete in about 3% of male infants. Men with a history of cryptorchidism face a risk of developing testicular cancer that is approximately 3.7 to 7.5 times higher than the general population.
The increased risk stems from an underlying abnormality in the testicle itself, not just its position. The risk is notably higher if the testicle remained in the abdomen compared to one that was only partially descended in the groin area. While a surgery called orchiopexy can move the testicle into the scrotum, which may reduce the cancer risk by half, it does not completely eliminate the chance of the cancer developing later in life.
A personal history of having had testicular cancer in one testicle is another strong predictor for the development of a new tumor in the remaining testicle. This risk requires ongoing surveillance after initial treatment. Genetic predisposition also plays a role, as having a close relative with the disease significantly elevates risk.
For instance, a man’s risk is increased two- to four-fold if his father had testicular cancer, and this risk rises eight- to twelve-fold if a brother has been diagnosed. These familial patterns suggest that inherited genetic factors are involved in the development of the disease. Despite these strong genetic links, most men who develop testicular cancer do not have a family history of the condition.
The Cellular Starting Point
Almost all testicular cancers originate in the germ cells, the specialized cells within the testes responsible for producing sperm. These tumors are broadly classified into two main categories: seminomas and non-seminomas. Seminomas tend to grow and spread more slowly, while non-seminomas are typically more aggressive.
The process of cancer development often begins with a precursor lesion known as Intratubular Germ Cell Neoplasia Unclassified (IGCNU), also referred to as Germ Cell Neoplasia in Situ (GCNIS). This stage involves abnormal germ cells that are confined entirely within the seminiferous tubules of the testicle. These abnormal cells have not yet broken through the tubule walls to become invasive cancer.
GCNIS is considered the common starting point for most testicular cancers in adolescents and young adults. A high percentage of men diagnosed with this precursor condition will go on to develop invasive cancer within a few years. The shift from GCNIS to a full-blown tumor involves further genetic changes, notably the consistent gain of genetic material from chromosome 12, which is frequently observed in invasive tumors.
Addressing External Factors and Misconceptions
While the primary risk factors are biological, many common questions revolve around external influences and lifestyle. Physical trauma or injury to the testicles, even severe enough to require medical attention, is not considered a cause of testicular cancer. An injury may prompt a man to seek medical care, leading to the discovery of an already existing tumor, but the trauma itself does not initiate the cancer.
Similar to injury, there is no evidence that factors like having a vasectomy, wearing tight clothing, or participating in strenuous physical activity increase the risk of developing the disease. These are common misconceptions not supported by scientific data. The disease is most common in men aged 15 and 35, with Caucasian men having a higher incidence rate than African American or Asian men.
Regarding environmental factors, the evidence is limited, but research is ongoing into potential influences during early development. Some theories suggest that in utero exposure to elevated estrogens or endocrine-disrupting chemicals (EDCs) may play a role in increasing susceptibility. However, these environmental factors are not established causes, and the reasons for the steady increase in testicular cancer incidence over the past decades are still not fully understood.
Other minor risk factors include medical conditions like Klinefelter syndrome and HIV infection, which are associated with increased susceptibility. Ultimately, while certain factors predispose a person to the disease, the exact combination of genetic and developmental events that cause a germ cell to become cancerous remains the focus of ongoing scientific investigation.