Testicular cancer begins before birth, when embryonic germ cells fail to mature properly and remain dormant until puberty triggers their growth. It is the most common cancer in young men aged 20 to 34, who account for 51% of new diagnoses. While no single factor explains every case, the causes involve a mix of prenatal development, genetics, and environmental exposures that interact in ways researchers are still untangling.
How Testicular Cancer Develops
Nearly all testicular cancers are germ cell tumors, meaning they arise from the cells that normally produce sperm. The process starts with a precursor condition called germ cell neoplasia in situ (GCNIS), where embryonic germ cells, either primordial germ cells or their slightly more developed form called gonocytes, get stuck during fetal development and never fully mature. These stalled cells sit quietly in the testicle throughout childhood.
At puberty, rising hormone levels create conditions for these abnormal cells to start multiplying. The support cells surrounding them (called Sertoli cells) begin to lose their normal adult function, progressively breaking down the protective barrier within the testicle. Research from the National Institutes of Health shows this breakdown is a two-way street: the precancerous cells actually cause the surrounding support cells to revert to a more primitive, fetal-like state, which in turn gives the abnormal germ cells more room to proliferate. Over time, this cycle allows GCNIS to progress into invasive cancer.
Undescended Testicles
Cryptorchidism, when one or both testicles fail to descend into the scrotum before birth, is the strongest established risk factor. A testicle that remains in the abdomen faces a cancer risk roughly 40 times higher than a normally positioned one. Even after surgical correction, the overall risk remains elevated, estimated at 3.7 to 7.5 times that of the general population.
The reason likely ties back to the same developmental disruption that causes the cancer itself. An undescended testicle is exposed to higher body temperatures and an abnormal hormonal environment during critical stages of fetal development, both of which can interfere with normal germ cell maturation. Surgical correction (orchiopexy) lowers the risk but doesn’t eliminate it, reinforcing the idea that the underlying developmental problem occurs before birth.
Genetic Susceptibility
Having a father or brother with testicular cancer significantly raises your risk, and researchers have identified specific genetic variants that explain part of this pattern. A landmark genome-wide study published in Nature Genetics found that variations in the KITLG gene on chromosome 12 tripled the risk of testicular cancer per copy of the risk variant. Men carrying two copies of this variant faced more than a fourfold increase in risk. KITLG produces a protein that plays a central role in germ cell development, so variants affecting its function align with the theory that disrupted germ cell maturation is the root cause.
A second gene region near SPRY4 on chromosome 5 also contributes, increasing risk by about 40% per copy of the risk variant and up to 80% in men carrying two copies. Unlike many cancers driven by rare mutations, testicular cancer susceptibility comes largely from common genetic variants that individually have modest effects but compound when inherited together. This helps explain why the cancer clusters in families without following a simple inheritance pattern.
Prenatal Hormone Environment
Conditions inside the womb during pregnancy appear to set the stage for testicular cancer decades later. This is the foundation of the testicular dysgenesis syndrome hypothesis, which proposes that cryptorchidism, certain genital abnormalities, poor sperm quality, and testicular cancer all stem from the same disruption of fetal testicular development.
Maternal hormone levels during pregnancy offer one window into this process. Research tracking hormone levels in pregnant women found that lower maternal testosterone levels may increase testicular cancer risk in sons. The relationship between maternal estrogen and risk is more complex: low birth weight, which has been linked to higher testicular cancer risk in multiple studies, correlates with lower estrogen levels during pregnancy. High birth weight, which may also carry some risk, correlates with higher estrogen. Both pathways could plausibly interfere with normal germ cell development, though through different mechanisms.
Environmental and Chemical Exposures
Endocrine disruptors, chemicals that mimic or interfere with the body’s hormones, are suspected contributors, particularly when exposure occurs during fetal development. Phthalates (found in plastics and personal care products) and other industrial chemicals have been linked to components of testicular dysgenesis syndrome in some human studies, though proving a direct causal relationship is difficult for ethical reasons. You can’t deliberately expose pregnant women to chemicals to see what happens, so much of the evidence comes from animal studies and population-level observations.
One chemical class with stronger human evidence is PFAS, the “forever chemicals” found in nonstick coatings, waterproof fabrics, and firefighting foam. A study of U.S. Air Force servicemen by the National Cancer Institute found that elevated blood levels of one specific PFAS compound, PFOS, was associated with higher testicular cancer risk. The study compared 530 servicemen diagnosed with testicular cancer to 530 matched controls using blood samples taken before diagnosis. Servicemen who had worked as firefighters or were stationed at bases with PFAS-contaminated water had higher blood levels of these chemicals.
Race, Ethnicity, and Rising Rates
Testicular cancer incidence in the U.S. has been climbing, rising from 4.71 per 100,000 men in 1992 to 6.22 per 100,000 in 2021. Historically, non-Hispanic white men have had the highest rates, but that pattern is shifting. Hispanic men now match non-Hispanic white men in incidence, with rates increasing by an average of 3% per year. Hispanic men also tend to be diagnosed younger and at more advanced stages.
Black men have historically had lower rates, though the reasons remain unclear. The racial and ethnic differences point to a combination of genetic susceptibility and environmental exposures that vary across populations. The rapid increase among Hispanic men, too fast to be explained by genetics alone, suggests environmental or lifestyle factors are playing a growing role.
Other Medical Conditions
Men with Klinefelter syndrome (an extra X chromosome) face an estimated 19-fold increased risk of germ cell tumors compared to the general population, though the pattern differs from typical testicular cancer. About 85% of germ cell tumors in men with Klinefelter syndrome develop outside the testicles, most commonly in the chest (mediastinum), rather than in the gonads themselves.
A previous testicular cancer diagnosis in one testicle also raises the risk of developing cancer in the other testicle, further supporting the idea that the underlying cause is a systemic developmental issue rather than something happening to one testicle in isolation. Men born with abnormalities of the urethra (hypospadias) or those with fertility problems also face modestly elevated risk, consistent with the testicular dysgenesis syndrome framework that links these conditions to a shared origin in fetal development.
Why It Peaks in Young Men
The age pattern of testicular cancer is unusual. Most cancers become more common with age as DNA damage accumulates over a lifetime. Testicular cancer peaks between ages 20 and 34, then declines. This makes sense given its origin: the precancerous cells are already present at birth, and puberty provides the hormonal trigger for their growth. By the time a man reaches his 40s, the window of vulnerability has largely passed. The cancer isn’t caused by decades of wear and tear. It’s the delayed consequence of something that went wrong before he was born.