What are the risk factors for testicular cancer?
Scientists have found few risk factors that make someone more likely to develop testicular cancer. Even if someone has one or more risk factors for this disease, it’s impossible to know for sure how much that risk factor contributes to developing the cancer. Also, most boys and men with testicular cancer do not have any of the known risk factors. Factors that may increase your risk of testicular cancer include:
Age
More than half of testicular cancer diagnoses occur in men between the ages of 20 and 45. However, men of any age can develop this disease, including men as young as 15, so it is important that any man with symptoms of testicular cancer visit the doctor.Cryptorchidism
Cryptorchism is an undescended testicle, in which one or both testicles do not move down into the scrotum before birth as they should. Men with this condition have an increased risk of developing testicular cancer. This risk may be lowered if surgery is used to correct the condition before the boy reaches puberty. Some doctors have recommended that cryptorchidism be corrected when a boy is very young, between six and 15 months, in order to reduce the risk of infertility, which is the inability to produce children. Because cryptorchidism is often corrected at a young age, many men may not know if they had the condition.Ethnicity and Race
The risk of testicular cancer among white men is about 4 to 5 times that of black men and more than 3 times that of Asian-American men. The risk for Hispanics/Latinos and American Indians falls between that of Asians and non-Hispanic/Latino whites. The reason for these differences is not known. Worldwide, the risk of developing this disease is highest among men living in the United States and Europe and lowest among men living in Africa or Asia.Family history
A family history of testicular cancer increases the risk. If a man has the disease, there is an increased risk that one or more of his brothers or sons will also develop it. But only a small number of testicular cancers occur in families. Most men with testicular cancer do not have a family history of the disease.Oestrogen exposure in utero
• Birth order and number of siblingsTesticular cancer risk is 8% higher in firstborns, and risk decreases with increasing birth order, a meta-analysis showed. It is also 25% higher in males with no siblings versus those with 4+ siblings, and risk decreases with increasing number of siblings. Testicular cancer risk is 22-31% higher in males with a twin, meta-analyses have shown. These attributes are associated with higher oestrogen levels in utero, but also with delayed childhood exposure to infections (linked with some other cancers), and parental subfertility, so the root cause remains unclear.
• Diethylstilbestrol
In utero exposure to synthetic oestrogen diethylstilbestrol (DES) is classified by IARC as a possible cause of testicular cancer, based on limited evidence. Testicular cancer risk may be around doubled in males exposed to DES in utero, though in meta-analysis the association was not significant. Cryptorchidism is around twice as common in DES-exposed men, a cohort study showed.
• Events during pregnancy and at birth
Testicular cancer risk is 33% higher in men whose mother had bleeding during pregnancy, a meta-analysis showed. It is 31% higher in men born prematurely, a meta-analysis showed; and may be around fourfold higher in those born extremely prematurely (weeks gestational age), a large cohort study showed.31 But testicular cancer risk is not associated with maternal nausea (though one study suggests an association with severe vomiting during pregnancy), hypertension or pre-eclampsia during pregnancy. Nor is it associated with delivery (breech or caesarean), maternal age or body mass index (BMI). Hormonal factors are implicated in some of these events/conditions.
Other medical conditions
• HIV/AIDS infectionSome evidence has shown that men infected with the human immunodeficiency virus (HIV), particularly those with AIDS, are at increased risk. No other infections have been shown to increase testicular cancer risk.
• Inguinal hernia
Testicular cancer risk is 37-63% higher in males with inguinal hernia (protrusion of part of the bowel through abdominal wall), a meta-analysis and large cohort-study showed.
Other testicular conditions
• HypospadiaTesticular cancer risk is 88-141% higher in males with hypospadia (abnormality of the penis and urethra), a meta-analysis and large cohort study showed.
• Low fertility
Testicular cancer risk is 59% higher in subfertile men (without cryptorchidism), compared with men with normal fertility levels, a meta-analysis showed. However this may be an underestimate, because subfertility was not limited to known male factor subfertility. A study including only men with known male factor subfertility found testicular cancer risk was around threefold increased in this population, but this study did not control for cryptorchidism. It appears that subfertility and testicular cancer may share causes, though subfertility as an early manifestation of testicular cancer (reverse causation) remains a possibility.
• Testicular dysgenesis syndrome
It has been proposed that testicular cancer, cryptorchidism, hypospadia and impaired sperm production/subfertility are all products of disturbed gonadal development in utero, and so should be considered together as testicular dysgenesis syndrome (TDS). There is some evidence that the TDS constituent conditions have similar incidence patterns. However it remains unclear whether they have a shared cause (e.g. in utero exposure to endocrine disruptors), or whether the conditions each affect the risk of one another.
Previous testicular cancer
Testicular cancer risk is 12-18 times higher in men with previous testicular cancer, compared with the general population, large cohort studies show. 2-4% of men with previous testicular cancer will develop cancer in their remaining testicle with 20 years. The risk of second testicular cancer is lower in men whose primary testicular cancer was advanced at diagnosis, probably because cisplatin-based chemotherapy (more like to be used in advanced cases) delays tumour development.Smoking
Testicular cancer risk may be increased in males whose mother smoked during pregnancy, but evidence is conflicting. Studies which assessed smoking indirectly (population smoking rates or maternal lung cancer) have found an association, while studies using self-report or medical records smoking data found no association.Testicular carcinoma in situ
This condition does not cause a lump in the testicles or any other symptoms. It isn’t clear how often carcinoma in situ (CIS) in the testicles progresses to cancer. In some cases, CIS is found in men who have a testicular biopsy to evaluate infertility or have a testicle removed because of cryptorchidism. Doctors in Europe are more likely than the doctors in this country to look for CIS. This may be why the numbers for diagnosis and progression of CIS to cancer are lower in the United States than in parts of Europe.Since we don’t know how often CIS becomes true (invasive) cancer, it isn’t clear if treating CIS is a good idea. Some experts think that it may be better to wait and see if the disease gets worse or becomes a true cancer. This could allow many men with CIS to avoid the risks and side effects of treatment. When CIS is treated, radiation or surgery (to remove the testicle) is used.
Undescended testicle
One of the main risk factors for testicular cancer is a condition called cryptorchidism, or undescended testicle(s). This means that one or both testicles fail to move from the abdomen (belly) into the scrotum before birth. Males with cryptorchidism are several times more likely to get testicular cancer than those with normally descended testicles.Normally, the testicles develop inside the abdomen of the fetus and they go down (descend) into the scrotum before birth. In about 3% of boys, however, the testicles do not make it all the way down before the child is born. Sometimes the testicle remains in the abdomen. In other cases, the testicle starts to descend but remains stuck in the groin area. Most of the time, undescended testicles continue moving down into the scrotum during the child’s first year of life. If the testicle has not descended by the time a child is a year old, it probably won’t go down on its own. Sometimes a surgical procedure known as orchiopexy is needed to bring the testicle down into the scrotum.
The risk of testicular cancer may be somewhat higher for men whose testicle stayed in the abdomen as opposed to one that has descended at least partway. If cancer does develop, it is usually in the undescended testicle, but about 1 out of 4 cases occur in the normally descended testicle. Because of this, some doctors conclude that cryptorchidism doesn’t actually cause testicular cancer but that there is something else that leads to both testicular cancer and abnormal positioning of one or both testicles.
Orchiopexy may reduce the risk of testicular cancer if it is done when a child is younger, but it is not as clear if it is helpful if the child is older. The best time to do this surgery is not clear. Experts in the United States recommend that orchiopexy be done soon after the child’s first birthday for reasons (such as fertility) that are not related to cancer.
Other risk factors
• AsbestosRisk of paratesticular mesothelioma (a rare type of testicular cancer) may be associated with past exposure to asbestos, case series indicate; however, evidence is sparse.
• Body weight
Testicular cancer risk is 8% lower in overweight men (BMI 30+) compared with those of a healthy weight (BMI 25-29.9), a meta-analysis showed.
• Height
Testicular cancer risk is 11-13% higher per 5cm increment in height, a meta-analysis and a pooled analysis of Nordic data showed
• Late puberty
Testicular cancer risk is 16-19% lower in men who started puberty later in comparison with their peers, a meta-analysis showed. No association with early puberty was found.
Factors not shown to be associated with testicular cancer risk
• Illnesses, infections and medicationsTesticular cancer risk is not increased in males who have had mumps or mumps orchitis (pain and swelling of the testicles), a meta-analysis showed. HPV infection is probably not linked with testicular cancer risk, although evidence is limited. Testicular cancer risk does not appear to be increased in users of antidepressant medications.
• Microlithiasis
Testicular cancer risk is not increased in men with microlithiasis (small calcium deposits in the testes) who are otherwise healthy, meta-analyses have shown. But in men referred for scrotal ultrasound because of other testicular cancer risk factors (e.g. cryptorchidism, relevant cancer history, or low fertility), microlithiasis is associated with an 8.5-fold increased testicular cancer risk.
• Occupational exposure
Despite extensive research, evidence on testicular cancer risk in relation to occupational exposures in adulthood remains insufficient to draw firm conclusions. Testicular cancer risk does not appear to be elevated with occupational exposure to ionising radiation, a systematic review showed. Polychlorinated biphenyls, pesticides and phthalates may affect oestrogen levels and so impact on testicular cancer risk, however evidence remains unclear.
• Vasectomy and injury
Testicular cancer risk is not elevated in men who have had a vasectomy, a large cohort study showed. Any association with testicular injury is thought to reflect recall bias or reverse causality (cancer detected incidentally during investigations for the injury)