Cancer Research UK : Testicular Cancer risk factors

Testicular Cancer risk factors

This page presents information on the risk factors for testicular cancer.

The dramatic increase in the incidence of testicular cancer has led to an intense search for its causes, but, as yet, no preventable risk factors have been found. Both environmental and genetic factors are likely to be involved.

Some groups of men are at increased risk of developing testicular cancer (Table 4.1).

Table 4.1: Known risk factors for testicular cancer

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The risks for testicular cancer associated with age and race have already been described in the Incidence section. A previous diagnosis of testicular cancer increases the risk of developing a subsequent (metachronous) testicular tumour by around 12-fold.1

Men with a previous extragonadal germ cell tumour (GCT) also have a higher risk.2 Untreated carcinoma in situ (CIS)of the testis will almost certainly progress to malignancy: around half of all men diagnosed with CIS of the testis will develop testicular cancer within five years.3,4

Cryptorchism, a common congenital abnormality in males - at birth 6% of all male babies have undescended testes but most of these descend spontaneously by 3 months by which time only 1.6% of babies still have one or more undescended testes, or maldescent testicle (MDT), is one of a range of testicular abnormalities known to increase the risk of testicular cancer.

About 10% of GCT patients have a history of this condition. Cryptorchism is associated with a two- to four-fold increased risk of testicular cancer in most studies, with higher risk for bilateral undescended testes.5

Correction of cryptorchism at a young age by orchidopexy, particularly before the age of four and at latest by the age of 10 (ie before puberty), reduces risk of testicular cancer, but it still remains higher than that for the general population. Cryptorchism is also associated with CIS of the testis, with around 2–3% of men with a history of cryptorchism at risk of developing CIS.6 Cryptorchism is more common in low birth weight babies, a characteristic associated with an increased risk of testicular cancer.7,8

Other urological maldevelopments associated with an increased risk of testicular cancer include inguinal hernia and hydrocoele (a collection of fluid around the testicles).9

More recently the diagnosis of microlithasis (micro-calcifications in the testis detected by ultrasound) has been associated with an increase in risk of testicular cancer, though the precise relationship remains to be determined.10-12

It has been suggested that population trends for problems with male reproductive health (including an increase in MDT,13 decreasing sperm quality, 14 and increasing rates of testicular cancer) may have a common, but as yet unproven, aetiology 15,16 Low fertility in general is linked to a higher risk of testicular cancer and CIS.17,19 There is some evidence that brothers of men with testicular cancer have reduced fertility.20

Inherited genetic factors play a role in a small percentage of testicular cancer patients. More information is in the Molecular biology and genetics section.21

It is thought that GCTs are initiated during foetal development, most likely in the first trimester, and that they progress to invasive cancer under the influence of adult hormones.22,23 Research has focused on maternal factors which could influence foetal development.

Of particular interest is the relationship between high levels of circulating oestrogen and a number of male reproductive disorders that are increasing in frequency, including cryptorchism, urethral abnormalities, poor semen quality and testicular cancer.24 Indirect evidence supports this oestrogen over-exposure hypothesis. Conditions that increase foetal exposure to oestrogen, including first pregnancy,25 dizygotic twins and severe maternal nausea,26 are also associated with increased risk of testicular cancer. However, epidemiological studies do not consistently confirm this association and more research is needed to clarify the role of in utero hormonal exposure.

Low birth weight babies and babies who are small for gestational age are at increased risk of testicular cancer, supporting the theory that prenatal influences are important.7,27

Evidence on maternal smoking is conflicting. A strong correlation has been identified between female smoking trends and rates of testicular cancer in Nordic countries28 and a positive association with maternal lung cancer has been observed in Sweden.29

However, one case-control study showed a significant reduction in risk of testicular cancer in offspring of women who smoke heavily30 while others report no association.7, 31, 32

Increased adult height,33-35 and early puberty 36,37 have also been associated with increased risk, both of which may be connected to hormonal and dietary factors. Population trends towards increasing adult height and earlier age at puberty are consistent with the rising trends of testicular cancer incidence.

Case-control studies have reported a positive association with increased consumption of dietary fat, particularly milk and cheese,38,39 and a correlation study in 42 countries found a strong correlation between milk and cheese consumption and testicular cancer incidence.40

Many occupations have been linked to increased testicular cancer risk, but the specific risks are not clear.5

References for testicular cancer risk factors

Fossa, S.D., et al., Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst, 2005. 97(14): p. 1056-66.
Hartmann, J.T., et al., Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.<.a> J Natl Cancer Inst, 2001. 93(22): p. 1733-8.

Giwercman, A., J. Muller, and N.E. Skakkeboek, Cryptorchidism and testicular neoplasia. Horm Res, 1988. 30(4-5): p. 157-63.
Jorgensen, N., et al., Clinical and biological significance of carcinoma in situ of the testis. Cancer Surv, 1990. 9(2): p. 287-302.
Garner, M.J., et al., Epidemiology of testicular cancer: an overview. Int J Cancer, 2005. 116(3): p. 331-9.
Giwercman, A., et al., Prevalence of carcinoma in situ and other histopathological abnormalities in testes of men with a history of cryptorchidism. J Urol, 1989. 142(4): p. 998-1001: discussion 1001-2.
Coupland, C.A., et al., Maternal risk factors for testicular cancer: a population-based case-control study (UK). Cancer Causes Control, 2004. 15(3): p. 277-83.
English, P.B., et al., Parental and birth characteristics in relation to testicular cancer risk among males born between 1960 and 1995 in Calif ornia (United States). Cancer Causes Control, 2003. 14(9): p. 815-25.
Tollerud, D.J., et al., Familial testicular cancer and urogenital developmental anomalies. Cancer, 1985. 55(8): p. 1849-54.
Miller, F.N., et al., Testicular calcification and microlithiasis: association with primary intra-testicular malignancy in 3,477 patients. Eur Radiol, 2007. 17(2): p. 363-369.
Bennett, H.F., et al., Testicular microlithiasis: US follow-up. Radiology, 2001. 218(2): p. 359-63.
Ganem, J.P.,Testicular microlithiasis. Curr Opin Urol, 2000. 10(2): p. 99-103.
Boisen, K.A., et al., Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet, 2004. 363(9417): p. 1264-9.
Carlsen, E., et al., Evidence for decreasing quality of semen during past 50 years. Bmj, 1992. 305(6854): p. 609-13.
Skakkebaek, N.E., E. Rajpert-De Meyts, and K.M. Main, Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod, 2001. 16(5): p. 972-8.
Skakkebaek, N.E., Testicular dysgenesis syndrome: new epidemiological evidence. Int J Androl, 2004. 27(4): p. 189-91.
Jacobsen, R., et al., Risk of testicular cancer in men with abnormal semen characteristics: cohort study. Bmj, 2000. 321(7264): p. 789-92.
Doria-Rose, V.P., M.L. Biggs, and N.S. Weiss, Subfertility and the risk of testicular germ cell tumors (United States). Cancer Causes Control, 2005. 16(6): p. 651-6.
Raman, J.D., C.F. Nobert, and M. Goldstein, Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol, 2005. 174(5): p. 1819-22; discussion 1822.
Richiardi, L. and O. Akre, Fertility Among Brothers of Patients with Testicular Cancer. Cancer Epidemiol Biomarkers Prev, 2005. 14(11): p. 2557-2562.
Hemminki, K. and X. Li, Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br J Cancer, 2004. 90(9): p. 1765-70.
Horwich, A., J. Shipley, and R. Huddart, Testicular germ-cell cancer. The Lancet, 2006. 367(9512): p. 754.
Oosterhuis, J.W. and L.H. Looijenga, Current views on the pathogenesis of testicular germ cell tumours and perspectives for future research: highlights of the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis. Apmis, 2003. 111(1): p. 280-9.
Sharpe, R.M. and N.E. Skakkebaek, Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet, 1993. 341(8857): p. 1392-5.
Westergaard, T., et al., Testicular cancer risk and maternal parity: a population-based cohort study. Br J Cancer, 1998. 77(7): p. 1180-5.
Swerdlow, A.J., et al., Risks of breast and testicular cancers in young adult twins in England and Wales: evidence on prenatal and genetic aetiology. Lancet, 1997. 350(9093): p. 1723-8.
Richiardi, L., et al., Body Size at Birth and Adulthood and the Risk for Germ-cell Testicular Cancer. Cancer Epidemiol Biomarkers Prev, 2003. 12(7): p. 669-673.
Pettersson, A., et al., Women smoking and testicular cancer: One epidemic causing another? Int J Cancer, 2004. 109(6): p. 941-4.
Kaijser, M., et al., Maternal lung cancer and testicular cancer risk in the offspring. Cancer Epidemiol Biomarkers Prev, 2003. 12(7): p. 643-6.
Weir, H.K., et al., Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer. Int J Cancer, 2000. 87(3): p. 438-43.
Moller, H. and N.E. Skakkebaek, Risks of testicular cancer and cryptorchidism in relation to socio-economic status and related factors: case-control studies in Denmark. Int J Cancer, 1996. 66(3): p. 287-93.
Chen, Z., et al., Risk of childhood germ cell tumors in association with parental smoking and drinking. Cancer, 2005. 103(5): p. 1064-71.
Rasmussen, F., et al., Birth weight, adult height, and testicular cancer: cohort study of 337,249 Swedish young men. Cancer Causes Control, 2003. 14(6): p. 595-8.
Richiardi, L., et al., Body size at birthand adulthood and the risk for germ-cell testicular cancer. Cancer Epidemiol Biomarkers Prev, 2003. 12(7): p. 669-73.
Dieckmann, K.P. and U. Pichlmeier, Is risk of testicular cancer related to body size? Eur Urol, 2002. 42(6): p. 564-9.
Weir, H.K., N. Kreiger, and L.D. Marrett, Age at puberty and risk of testicular germ cell cancer (Ontario, Canada). Cancer Causes Control, 1998. 9(3): p. 253-8.
Aetiology of testicular cancer: association with congenital abnormalities, age at puberty, infertility, and exercise. United Kingdom Testicular Cancer Study Group. Bmj, 1994. 308(6941): p. 1393-9.
Garner, M.J., et al., Dietary risk factors for testicular carcinoma. Int J Cancer, 2003. 106(6): p. 934-41.
Davies, T.W., et al., Adolescent milk, dairy product and fruit consumption and testicular cancer. Br J Cancer, 1996. 74(4): p. 657-60.
Ganmaa, D., et al., Incidence and mortality of testicular and prostatic cancers in relation to world dietary practices. Int J Cancer, 2002. 98(2): p. 262-7.

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Testicular Cancer risk factors

References for testicular cancer risk factors

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