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Testicular cancer risk factors

The key risk factors for testicular cancer are discussed on this page. The causes of testicular cancer are not well understood, despite substantial research; the most well-established risk factor for testicular cancer is cryptorchidism. Testicular cancer risk is linked with age and ethnicity, as shown on the incidence statistics page.

Meta-analyses and systematic reviews are cited where available, as they provide the best overview of all available research and most take study quality into account. Individual case-control and cohort studies are reported where such aggregated data are lacking.

Testicular cancer risk factors overview

The International Agency for Research on Cancer (IARC) evaluates evidence on the carcinogenic risk to humans of a number of exposures including tobacco, alcohol, infections, radiation, occupational exposures, and medications.1 The World Cancer Research Fund/America Institute of Cancer Research (WCFR/AICR) evaluates evidence for other exposures including diet, overweight and obesity and physical exercise.2 IARC and WCRF/AICR evaluations are the gold standard in cancer epidemiology. Their conclusions about testicular cancer risk factors are shown in Table 4.1. The WCRF/AICR evaluation does not include testicular cancer because the evidence is very limited.

Table 4.1: IARC Evaluations of Testicular Cancer Risk Factors

Increases risk ('sufficient' or 'convincing' evidence)1 May increase risk ('limited' or 'probably' evidence) Decreases risk ('sufficient' or 'convincing' evidence) May decrease risk ('limited' or 'probable' evidence)

-

  • Diethylstilbestrol (exposure in utero)

-

-

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Age

The risk of testicular cancer is higher in younger men than in older men. Find out more about the association between age and testicular cancer incidence.

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Ethnicity

The risk of testicular cancer is higher in white men than in men from other ethnic groups. 

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Cryptorchidism

Testicular cancer risk is around 3-4 times higher in males with cryptorchidism (also known as undescended testicle, a condition where one or both testes fails to descend into the scrotum in the first year of life), meta-analyses have shown.3,4

In unilateral cryptorchidism (where only one testicle is undescended), testicular cancer risk is 6.3 times increased in the undescended testicle, and 1.7 times increased in the descended one, compared with general population rates, a meta-analysis showed.5

Testicular cancer risk is around 2-6 times higher in males whose cryptorchidism was surgically corrected (orchiopexy) after age 11-13 or not at all, compared with those who had the procedure at a younger age, a meta-analysis and large cohort study showed.6,7

Testicular cancer risk appears to be increased in males with polyorchidism (more than two testes), although this is probably closely linked with cryptorchidism.8

The mechanism of association between cryptorchidism and testicular cancer risk remains unclear. The difference in risk by age at surgery suggests that cryptorchidism-related events at puberty as well as those in utero are implicated.5,6

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Other testicular conditions

Hypospadia

Testicular cancer risk is 88-141% higher in males with hypospadia (abnormality of the penis and urethra), a meta-analysis and large cohort study showed.9,10

Low fertility

Testicular cancer risk is 59% higher in subfertile men (without cryptorchidism), compared with men with normal fertility levels, a meta-analysis showed.11 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.12 It appears that subfertility and testicular cancer may share causes, though subfertility as an early manifestation of testicular cancer (reverse causation) remains a possibility.13,14

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).14 There is some evidence that the TDS constituent conditions have similar incidence patterns.15-17 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.14

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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.18-20,56 2-4% of men with previous testicular cancer will develop cancer in their remaining testicle with 20 years.18-20 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.20

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Testicular carcinoma in situ

Testicular carcinoma in situ (CIS), also known as intratubular germ cell neoplasia (IGCN) or testicular intraepithelial neoplasia (TIN), is a precursor for testicular cancer. Around half of men with CIS will develop testicular cancer within 5 years, without treatment.21,22

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Other medical conditions

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.4,10

HIV/AIDS

Testicular cancer risk is 35-79% higher in men with HIV/AIDS compared with the general population, meta-analyses have shown; however this risk increase may no longer be significant in the era of highly active antiretroviral therapy (HAART) for HIV.23-25

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Family history

A small proportion of men with testicular cancer have a family history of the disease.26 Testicular cancer risk is around 4-5 times higher in men whose father was diagnosed with the disease, large cohort studies have shown.27,28 Testicular cancer risk is 8-9 times higher in men with a brother diagnosed with the disease.

Testicular cancer risk may be elevated in those with family history of non-Hodgkin lymphoma or oesophageal cancer, but evidence remains limited.28

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Oestrogen exposure in utero

Birth order and number of siblings

Testicular cancer risk is 8% higher in firstborns, and risk decreases with increasing birth order, a meta-analysis showed.29 It is also 25% higher in males with no siblings versus those with 4+ siblings, and risk decreases with increasing number of siblings.29 Testicular cancer risk is 22-31% higher in males with a twin, meta-analyses have shown.4,30 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.29

Events during pregnancy and at birth

Testicular cancer risk is 33% higher in men whose mother had bleeding during pregnancy, a meta-analysis showed.29 It is 31% higher in men born prematurely, a meta-analysis showed;4 and may be around fourfold higher in those born extremely prematurely (22-29 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.29,32 Nor is it associated with delivery (breech or caesarean), maternal age or body mass index (BMI).29,33 Hormonal factors are implicated in some of these events/conditions.

Diethylstilbestrol

In utero exposure to synthetic oestrogen diethylstilbestrol (DES) is classified by IARC as a possible cause of testicular cancer, based on limited evidence (Table 4.1).1 Testicular cancer risk may be around doubled in males exposed to DES in utero, though in meta-analysis the association was not significant.34 Cryptorchidism is around twice as common in DES-exposed men, a cohort study showed.35

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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,36,37 while studies using self-report or medical records smoking data found no association.38,39

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Other risk factors

Height

Testicular cancer risk is 11-13% higher per 5cm increment in height, a meta-analysis and a pooled analysis of Nordic data showed.40,41

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.40

Low birth weight is associated with increased risk of cryptorchidism, but a direct link with testicular cancer risk has not been consistently demonstrated.14,42,43

Late puberty

Testicular cancer risk is 16-19% lower in men who started puberty later in comparison with their peers, a meta-analysis showed.44 No association with early puberty was found.

Asbestos

Risk of paratesticular mesothelioma (a rare type of testicular cancer) may be associated with past exposure to asbestos, case series indicate; however, evidence is sparse.54,55

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Factors not shown to be associated with testicular cancer risk

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.45,46 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.46

Occupational exposure

Despite extensive research, evidence on testicular cancer risk in relation to occupational exposures in adulthood remains insufficient to draw firm conclusions.47 Testicular cancer risk does not appear to be elevated with occupational exposure to ionising radiation, a systematic review showed.48 Polychlorinated biphenyls, pesticides and phthalates may affect oestrogen levels and so impact on testicular cancer risk, however evidence remains unclear.49

Illnesses, infections and medications

Testicular cancer risk is not increased in males who have had mumps or mumps orchitis (pain and swelling of the testicles), a meta-analysis showed.50 HPV infection is probably not linked with testicular cancer risk, although evidence is limited.25 Testicular cancer risk does not appear to be increased in users of antidepressant medications.51

Vasectomy and injury

Testicular cancer risk is not elevated in men who have had a vasectomy, a large cohort study showed.52 Any association with testicular injury is thought to reflect recall bias or reverse causality (cancer detected incidentally during investigations for the injury).53

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References for testicular cancer risk factors

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 105*. Available from: http://monographs.iarc.fr/ENG/Classification/index.php. Accessed October 2013.
  2. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR; 2007.
  3. Lip SZ, Murchison LE, Cullis PS, et al. A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life. Arch Dis Child 2013;98(1):20-6.
  4. Cook MB, Akre O, Forman D, et al. A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer--experiences of the son. Int J Epidemiol 2010; 39(6):1605-18.
  5. Akre O, Pettersson A, Richiardi L. Risk of contralateral testicular cancer among men with unilaterally undescended testis: a meta analysis. Int J Cancer 2009;124(3);687-9.
  6. Walsh TJ, Dall'Era MA, Croughan MS, et al. Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer. J Urol 2007;178(4 Pt 1):1440-6.
  7. Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007; 356(18) 1835-41.
  8. Bergholz R, Wenke K. Polyorchidism: a meta-analysis. J Urol 2009;182(5):2422-7.
  9. Schnack TH, Poulsen G, Myrup C, et al. Familial coaggregation of cryptorchidism, hypospadias, and testicular germ cell cancer: a nationwide cohort study. J Natl Cancer Inst 2010;102(3):187-92.
  10. Trabert B, Zugna D, Richiardi L, et al. Congenital malformations and testicular germ cell tumors. Int J Cancer 2013;133(8):1900-4.
  11. Peng X, Zeng X, Peng S, et al. The association risk of male subfertility and testicular cancer: a systematic review. PLoS One 2009;4(5):e5591.
  12. Walsh TJ, Croughan MS, Schembri M, et al. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 2009; 169(4) 351-6.
  13. Richiardi L, Akre O. Fertility Among Brothers of Patients with Testicular Cancer. Cancer Epidemiol Biomarkers Prev 2005; 14(11) 2557-2562.
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  15. Jørgensen N, Vierula M, Jacobsen R, et al. Recent adverse trends in semen quality and testis cancer incidence among Finnish men. Int J Androl 2011;34(4 Pt 2):e37-48.
  16. Skakkebaek NE, Rajpert-De Meyts E, Jørgensen N, et al. Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations. Int J Androl 2007;30(4):198-204.
  17. Gurney J, Sarfati D, Stanley J, et al. Do ethnic patterns in cryptorchidism reflect those found in testicular cancer? J Urol 2013;190(5):1852-7.
  18. Schaapveld M, van den Belt-Dusebout AW, Gietema JA, et al. Risk and prognostic significance of metachronous contralateral testicular germ cell tumours. Br J Cancer 2012;107(9):1637-43.
  19. Fosså SD, Chen J, Schonfeld SJ, et al. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 2005; 97(14) 1056-66.
  20. Andreassen KE, Grotmol T, Cvancarova MS, et al. Risk of metachronous contralateral testicular germ cell tumors: a population-based study of 7,102 Norwegian patients (1953-2007). Int J Cancer 2011;129(12):2867-74.
  21. Hoei-Hansen CE, Rajpert-De Meyts E, Daugaard G, et al. Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review. Ann Oncol 2005 16(6):863-8.
  22. von der Maase H, Rorth M, Walbom-Jorgensen S, et al. Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients. BMJ 1986;293:1398–1401.
  23. Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007; 370(9581):59-67
  24. Shiels MS, Cole SR, Kirk GD, et al. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr 2009;52(5):611-22.
  25. Yousif L, Hammer GP, Blettner M, et al. Testicular cancer and viral infections: a systematic literature review and meta-analysis. J Med Virol 2013;85(12):2165-75.
  26. Hemminki K, Sundquist J, Bermejo JL. How common is familial cancer? Ann Oncol. 2008 Jan;19(1):163-7.
  27. Hemminki K, Li X. Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br J Cancer 2004; 90(9) 1765-70.
  28. Nordsborg RB, Meliker JR, Wohlfahrt J, et al. Cancer in first-degree relatives and risk of testicular cancer in Denmark. Int J Cancer 2011;129(10):2485-91.
  29. Cook MB, Akre O, Forman D, et al. A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer--experiences of the mother. Int J Epidemiol 2009;38(6):1532-42.
  30. Neale RE, Carrière P, Murphy MF, et al. Testicular cancer in twins: a meta-analysis. Br J Cancer 2008;98(1):171-3.
  31. Crump C, Sundquist K, Winkleby MA, et al. Gestational age at birth and risk of testicular cancer. Int J Cancer 2012;131(2):446-51.
  32. Veenendaal MV, van Abeelen AF, Painter RC, et al. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. BJOG 2011;118(11):1302-13.
  33. Alam SS, Cantwell MM, Cardwell CR, et al. Maternal body mass index and risk of testicular cancer in male offspring: a systematic review and meta-analysis. Cancer Epidemiol 2010;34(5):509-15.
  34. Martin OV, Shialis T, Lester JN, et al. Testicular dysgenesis syndrome and the estrogen hypothesis: a quantitative meta-analysis. Environ Health Perspect 2008 ;116(2):149-57.
  35. Palmer JR, Herbst AL, Noller KL, et al. Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environ Health 2009 ;8:37.
  36. Pettersson A, Kaijser M, Richiardi L, et al. Women smoking and testicular cancer: One epidemic causing another? Int J Cancer 2004; 109(6) 941-4.
  37. Kaijser M, Akre O, Cnattingius S, et al. Maternal lung cancer and testicular cancer risk in the offspring. Cancer Epidemiol Biomarkers Prev 2003; 12(7) 643-6.
  38. Tuomisto J, Holl K, Rantakokko P, et al. Maternal smoking during pregnancy and testicular cancer in the sons: a nested case-control study and a meta-analysis. Eur J Cancer 2009;45(9):1640-8.
  39. Mongraw-Chaffin ML, Cohn BA, Anglemyer AT, et al. Maternal smoking, alcohol, and coffee use during pregnancy and son's risk of testicular cancer. Alcohol 2009;43(3):241-5.
  40. Lerro CC, McGlynn KA, Cook MB. A systematic review and meta-analysis of the relationship between body size and testicular cancer. Br J Cancer. 2010;103(9):1467-74.
  41. Wirén S, Häggström C, Ulmer H, et al. Pooled cohort study on height and risk of cancer and cancer death. Cancer Causes Control. 2013;25(2):151-9.
  42. Michos A, Xue F, Michels KB. Birth weight and the risk of testicular cancer: A meta-analysis. Int J Cancer 2007; 121(5):1123-31.
  43. Richiardi L, Pettersson A, Akre O. Genetic and environmental risk factors for testicular cancer. Int J Androl 2007;30(4):230-40.
  44. Maule M, Malavassi JL, Richiardi L. Age at puberty and risk of testicular cancer: a meta-analysis. Int J Androl 2012; 35(6):828-34.
  45. Richenberg J, Brejt N. Testicular microlithiasis: is there a need for surveillance in the absence of other risk factors? Eur Radiol. 2012;22(11):2540-6.
  46. Tan IB, Ang KK, Ching BC, et al. Testicular microlithiasis predicts concurrent testicular germ cell tumors and intratubular germ cell neoplasia of unclassified type in adults: a meta-analysis and systematic review. Cancer 2010;116(19):4520-32.
  47. Béranger R, Le Cornet C, Schüz J, et al. Occupational and environmental exposures associated with testicular germ cell tumours: systematic review of prenatal and life-long exposures. PLoS One 2013;8(10):e77130.
  48. Yousif L, Blettner M, Hammer GP, et al. Testicular cancer risk associated with occupational radiation exposure: a systematic literature review. J Radiol Prot 2010;30(3):389-406.
  49. McGlynn KA, Trabert B. Adolescent and adult risk factors for testicular cancer. Nat Rev Urol 2012;9(6):339-49.
  50. Trabert B, Graubard BI, Erickson RL, et al. Childhood infections, orchitis and testicular germ cell tumours: a report from the STEED study and a meta-analysis of existing data. Br J Cancer 2012;106(7):1331-4.
  51. Friedman GD, Schwalbe J, Achacoso N, et al. Antidepressants and testicular cancer. Cancer Causes Control 2014;25(2):251-8.
  52. Møller H, Knudsen LB, Lynge E. Risk of testicular cancer after vasectomy: cohort study of over 73,000 men. BMJ. 1994;309(6950):295-9.
  53. UK Testicular Cancer Study Group. Social, behavioural and medical factors in the aetiology of testicular cancer: results from the UK study. Br J Cancer 1994;70(3):513-20.
  54. Mensi C, Pellegatta M, Sieno C, et al. Mesothelioma of tunica vaginalis testis and asbestos exposure. BJU Int 2012;110(4):533-7.
  55. Alesawi AM, Levesque J, Fradet JV. Malignant mesothelioma of the tunica vaginalis testis: comprehensive review of literature and case report. J Clin Urol 2013; doi: 10.1177/2051415813511082.
  56. Rusner C, Streller B, Stegmaier C, et al. Risk of second primary cancers after testicular cancer in East and West Germany: A focus on contralateral testicular cancers. Asian J Androl. 2014 Mar-Apr;16(2):285-9.
Updated: 1 April 2014