Skip to main content
SpringerLink
Log in
Book cover

Pediatric Germ Cell Tumors pp 17–36Cite as

Epidemiology of Germ Cell Tumors

  • Chapter
  • First Online:

Part of the book series: Pediatric Oncology ((PEDIATRICO,volume 1))

Abstract

Pediatric malignant germ cell tumors (GCTs) represent approximately 3 % of childhood cancers. Incidence is increasing in certain subgroups, and the etiology remains poorly understood. Evidence suggests that GCTs, including those in adults, are initiated in utero. Thus, alterations in normal embryonic development are likely to be especially relevant to GCT etiology. Potential risk factors that have been evaluated for pediatric GCT include parental demographic characteristics; in utero exposure to hormones and pesticides; maternal reproductive history; parental smoking, occupation, and alcohol consumption; and congenital abnormalities (Chen et al., Int J Hyg Environ Health 209:31–40, 2006; Chen et al., Cancer 103:1064–1071, 2005a; Chen et al., Am J Epidemiol 162:858–867, 2005b; Fajardo-Gutierrez et al., Gac Med Mex 134:273–281, 1998; Johnston et al., Carcinogenesis 7:717–722, 1986; Shankar et al., Cancer 106:1169–1177, 2006; Shu et al., Cancer Causes Control 6:187–198, 1995; Swerdlow et al., Br J Cancer 55:571–577, 1987; Walker et al., Br J Cancer 57:418–422, 1988); however, none has emerged as a consistent risk factor. Family history of testicular cancer and cryptorchidism are two well-established risk factors for adult testicular GCT (Sarma et al., Testicular cancer. In: Schottenfeld D, Fraumeni Jr. JE (eds) Cancer epidemiology and prevention, 3rd edn. New York, Oxford University Press, pp 1159–1160, 2006). Genetic susceptibility is of particular interest for adult TGCTs given the strong evidence supporting a hereditary basis for this cancer (Forman et al., Br J Cancer 65:255–262, 1992), and recent genome-wide association studies have identified susceptibility alleles for TGCT in several genes with relevance to normal germ cell development (Kanetsky et al., Nat Genet 41:811–815, 2009; Kanetsky et al., Hum Mol Genet 20:3109–3117, 2011; Rapley, Int J Androl 30:242–250, 2007; Turnbull et al., Nat Genet 42:604–607, 2010). Malignant GCTs in adult females are extremely rare with incidence rates well below 1 per 100,000 women in most countries; therefore, little is known about the etiology of these tumors.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Agha MM, Williams JI, Marrett L, To T, Zipursky A, Dodds L (2005) Congenital abnormalities and childhood cancer. Cancer 103:1939–1948

    PubMed  Google Scholar 

  • Alanee S, Shukla A (2009) Paediatric testicular cancer: an updated review of incidence and conditional survival from the Surveillance, Epidemiology and End Results database. BJU Int 104:1280–1283

    PubMed  Google Scholar 

  • Baade P, Carriere P, Fritschi L (2008) Trends in testicular germ cell cancer incidence in Australia. Cancer Causes Control 19:1043–1049

    PubMed  Google Scholar 

  • Bergstrom R, Adami HO, Mohner M, Zatonski W, Storm H, Ekbom A, Tretli S, Teppo L, Akre O, Hakulinen T (1996) Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J Natl Cancer Inst 88:727–733

    CAS  PubMed  Google Scholar 

  • Bernstein L, Smith MA, Liu L, Deapen D, Friedman DL (1999) Germ cell, trophoblastic, and other gonadal neoplasms. In: Ries L, Smith MA, Gurney JG, Linet M, Tamra T, Young TL, Bunin GR (eds) Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. NIH Pub. No. 99-4649. National Cancer Institute, SEER Program, Bethesda, pp 125–137

    Google Scholar 

  • Bethel CA, Mutabagani K, Hammond S, Besner GE, Caniano DA, Cooney DR (1998) Nonteratomatous germ cell tumors in children. J Pediatr Surg 33:1122–1126; discussion 1126–1127

    CAS  PubMed  Google Scholar 

  • Biggs ML, Davis MD, Eaton DL, Weiss NS, Barr DB, Doody DR, Fish S, Needham LL, Chen C, Schwartz SM (2008) Serum organochlorine pesticide residues and risk of testicular germ cell carcinoma: a population-based case–control study. Cancer Epidemiol Biomarkers Prev 17:2012–2018

    CAS  PubMed  Google Scholar 

  • Biggs ML, Schwartz SM (2004) Differences in testis cancer survival by race and ethnicity: a population-based study, 1973–1999 (United States). Cancer Causes Control 15:437–444

    PubMed  Google Scholar 

  • Boisen KA, Main KM, Rajpert-De Meyts E, Skakkebaek NE (2001) Are male reproductive disorders a common entity? The testicular dysgenesis syndrome. Ann N Y Acad Sci 948:90–99

    CAS  PubMed  Google Scholar 

  • Bouskine A, Nebout M, Brucker-Davis F, Benahmed M, Fenichel P (2009) Low doses of bisphenol A promote human seminoma cell proliferation by activating PKA and PKG via a membrane G-protein-coupled estrogen receptor. Environ Health Perspect 117:1053–1058

    CAS  PubMed  Google Scholar 

  • Bouskine A, Nebout M, Mograbi B, Brucker-Davis F, Roger C, Fenichel P (2008) Estrogens promote human testicular germ cell cancer through a membrane-mediated activation of extracellular regulated kinase and protein kinase A. Endocrinology 149:565–573

    CAS  PubMed  Google Scholar 

  • Bray F, Richiardi L, Ekbom A, Forman D, Pukkala E, Cuninkova M, Moller H (2006a) Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries. Cancer Epidemiol Biomarkers Prev 15:652–658

    PubMed  Google Scholar 

  • Bray F, Richiardi L, Ekbom A, Pukkala E, Cuninkova M, Moller H (2006b) Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer 118:3099–3111

    CAS  PubMed  Google Scholar 

  • Bromen K, Stang A, Baumgardt-Elms C, Stegmaier C, Ahrens W, Metz KA, Jockel KH (2004) Testicular, other genital, and breast cancers in first-degree relatives of testicular cancer patients and controls. Cancer Epidemiol Biomarkers Prev 13:1316–1324

    PubMed  Google Scholar 

  • Brookfield KF, Cheung MC, Koniaris LG, Sola JE, Fischer AC (2009) A population-based analysis of 1037 malignant ovarian tumors in the pediatric population. J Surg Res 156:45–49

    PubMed  Google Scholar 

  • Brown LM, Pottern LM, Hoover RN (1986) Prenatal and perinatal risk factors for testicular cancer. Cancer Res 46:4812–4816

    CAS  PubMed  Google Scholar 

  • Bryant CS, Kumar S, Shah JP, Mahdi H, Ali-Fehmi R, Munkarah AR, Deppe G, Morris RT (2009) Racial disparities in survival among patients with germ cell tumors of the ovary – United States. Gynecol Oncol 114:437–441

    PubMed  Google Scholar 

  • Bullock BC, Newbold RR, McLachlan JA (1988) Lesions of testis and epididymis associated with prenatal diethylstilbestrol exposure. Environ Health Perspect 77:29–31

    CAS  PubMed  Google Scholar 

  • Chaki SP, Misro MM, Gautam DK, Kaushik M, Ghosh D, Chainy GB (2006) Estradiol treatment induces testicular oxidative stress and germ cell apoptosis in rats. Apoptosis 11:1427–1437

    CAS  PubMed  Google Scholar 

  • Chen Z, Robison L, Giller R, Krailo M, Davis M, Davies S, Shu XO (2006) Environmental exposure to residential pesticides, chemicals, dusts, fumes, and metals, and risk of childhood germ cell tumors. Int J Hyg Environ Health 209:31–40

    CAS  PubMed  Google Scholar 

  • Chen Z, Robison L, Giller R, Krailo M, Davis M, Gardner K, Davies S, Shu XO (2005a) Risk of childhood germ cell tumors in association with parental smoking and drinking. Cancer 103:1064–1071

    PubMed  Google Scholar 

  • Chen Z, Stewart PA, Davies S, Giller R, Krailo M, Davis M, Robison L, Shu XO (2005b) Parental occupational exposure to pesticides and childhood germ-cell tumors. Am J Epidemiol 162:858–867

    PubMed  Google Scholar 

  • Chia VM, Li Y, Goldin LR, Graubard BI, Greene MH, Korde L, Rubertone MV, Erickson RL, McGlynn KA (2009) Risk of cancer in first- and second-degree relatives of testicular germ cell tumor cases and controls. Int J Cancer 124:952–957

    CAS  PubMed  Google Scholar 

  • Chia VM, Quraishi SM, Devesa SS, Purdue MP, Cook MB, McGlynn KA (2010) International trends in the incidence of testicular cancer, 1973–2002. Cancer Epidemiol Biomarkers Prev 19:1151–1159

    PubMed  Google Scholar 

  • Clark AT (2007) The stem cell identity of testicular cancer. Stem Cell Rev 3:49–59

    CAS  PubMed  Google Scholar 

  • Cook MB, Akre O, Forman D, Madigan MP, Richiardi L, McGlynn KA (2009) A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer – experiences of the mother. Int J Epidemiol 38:1532–1542

    PubMed  Google Scholar 

  • Cook MB, Akre O, Forman D, Madigan MP, Richiardi L, McGlynn KA (2010) A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer – experiences of the son. Int J Epidemiol 39:1605–1618

    PubMed  Google Scholar 

  • Crockford GP, Linger R, Hockley S, Dudakia D, Johnson L, Huddart R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Albers P, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Forman D, Oliver T, Einhorn L, McMaster M, Kramer J, Greene MH, Weber BL, Nathanson KL, Cortessis V, Easton DF, Bishop DT, Stratton MR, Rapley EA (2006) Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. Hum Mol Genet 15:443–451

    CAS  PubMed  Google Scholar 

  • Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P (eds) (2007) Cancer incidence in five continents, vol IX. IARC, Lyon

    Google Scholar 

  • Cushing B, Giller R, Cullen JW, Marina NM, Lauer SJ, Olson TA, Rogers PC, Colombani P, Rescorla F, Billmire DF, Vinocur CD, Hawkins EP, Davis MM, Perlman EJ, London WB, Castleberry RP (2004) Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study – Pediatric Oncology Group 9049 and Children’s Cancer Group 888. J Clin Oncol 22:2691–2700

    CAS  PubMed  Google Scholar 

  • Czene K, Lichtenstein P, Hemminki K (2002) Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer 99:260–266

    CAS  PubMed  Google Scholar 

  • De Backer A, Madern GC, Pieters R, Haentjens P, Hakvoort-Cammel FG, Oosterhuis JW, Hazebroek FW (2008) Influence of tumor site and histology on long-term survival in 193 children with extracranial germ cell tumors. Eur J Pediatr Surg 18:1–6

    PubMed  Google Scholar 

  • Delbes G, Levacher C, Pairault C, Racine C, Duquenne C, Krust A, Habert R (2004) Estrogen receptor beta-mediated inhibition of male germ cell line development in mice by endogenous estrogens during perinatal life. Endocrinology 145:3395–3403

    CAS  PubMed  Google Scholar 

  • Dieckmann KP, Pichlmeier U (1997) The prevalence of familial testicular cancer: an analysis of two patient populations and a review of the literature. Cancer 80:1954–1960

    CAS  PubMed  Google Scholar 

  • Donovan PJ, de Miguel MP (2003) Turning germ cells into stem cells. Curr Opin Genet Dev 13:463–471

    CAS  PubMed  Google Scholar 

  • dos Santos Silva I, Swerdlow AJ (1991) Ovarian germ cell malignancies in England: epidemiological parallels with testicular cancer. Br J Cancer 63:814–818

    PubMed  Google Scholar 

  • dos Santos Silva I, Swerdlow AJ, Stiller CA, Reid A (1999) Incidence of testicular germ-cell malignancies in England and Wales: trends in children compared with adults. Int J Cancer 83:630–634

    PubMed  Google Scholar 

  • Dreifaldt AC, Carlberg M, Hardell L (2004) Increasing incidence rates of childhood malignant diseases in Sweden during the period 1960–1998. Eur J Cancer 40:1351–1360

    PubMed  Google Scholar 

  • Ducore JM, Parikh-Patel A, Gold EB (2004) Cancer occurrence in Southeast Asian children in California. J Pediatr Hematol Oncol 26:613–618

    PubMed  Google Scholar 

  • Einhorn LH, Donohue J (1977) Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87:293–298

    CAS  PubMed  Google Scholar 

  • Fajardo-Gutierrez A, Gomez-Gomez M, Danglot-Banck C, Alvarez-Contreras JJ, Yamamoto-Kimura L (1998) Risk factors for the development of germ cell tumors in children. Gac Med Mex 134:273–281

    CAS  PubMed  Google Scholar 

  • Figueroa JD, Sakoda LC, Graubard BI, Chanock S, Rubertone MV, Erickson RL, McGlynn KA (2008) Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors. Cancer Causes Control 19:917–929

    PubMed  Google Scholar 

  • Forman D, Oliver RT, Brett AR, Marsh SG, Moses JH, Bodmer JG, Chilvers CE, Pike MC (1992) Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. Br J Cancer 65:255–262

    CAS  PubMed  Google Scholar 

  • Fossa SD, Cvancarova M, Chen L, Allan AL, Oldenburg J, Peterson DR, Travis LB (2011) Adverse prognostic factors for testicular cancer-specific survival: a population-based study of 27,948 patients. J Clin Oncol 29:963–970

    PubMed  Google Scholar 

  • Frost G, Brown T, Harding AH (2011) Mortality and cancer incidence among British agricultural pesticide users. Occup Med (Lond) 61:303–310

    CAS  Google Scholar 

  • Giambartolomei C, Mueller CM, Greene MH, Korde LA (2009) A mini-review of familial ovarian germ cell tumors: an additional manifestation of the familial testicular germ cell tumor syndrome. Cancer Epidemiol 33:31–36

    PubMed  Google Scholar 

  • Giusti RM, Iwamoto K, Hatch EE (1995) Diethylstilbestrol revisited: a review of the long-term health effects. Ann Intern Med 122:778–788

    CAS  PubMed  Google Scholar 

  • Glazer ER, Perkins CI, Young JL Jr, Schlag RD, Campleman SL, Wright WE (1999) Cancer among Hispanic children in California, 1988–1994: comparison with non-Hispanic white children. Cancer 86:1070–1079

    CAS  PubMed  Google Scholar 

  • Gobel U, Schneider DT, Calaminus G, Haas RJ, Schmidt P, Harms D (2000) Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups. Ann Oncol 11:263–271

    CAS  PubMed  Google Scholar 

  • Hardell L, van Bavel B, Lindstrom G, Carlberg M, Dreifaldt AC, Wijkstrom H, Starkhammar H, Eriksson M, Hallquist A, Kolmert T (2003) Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer. Environ Health Perspect 111:930–934

    CAS  PubMed  Google Scholar 

  • Harms D, Janig U (1986) Germ cell tumours of childhood. Report of 170 cases including 59 pure and partial yolk-sac tumours. Virchows Arch A Pathol Anat Histopathol 409:223–239

    CAS  PubMed  Google Scholar 

  • Heimdal K, Olsson H, Tretli S, Flodgren P, Borresen AL, Fossa SD (1996a) Familial testicular cancer in Norway and southern Sweden. Br J Cancer 73:964–969

    CAS  PubMed  Google Scholar 

  • Heimdal K, Olsson H, Tretli S, Flodgren P, Borresen AL, Fossa SD (1996b) Risk of cancer in relatives of testicular cancer patients. Br J Cancer 73:970–973

    CAS  PubMed  Google Scholar 

  • Hemminki K, Chen B (2006) Familial risks in testicular cancer as aetiological clues. Int J Androl 29:205–210

    PubMed  Google Scholar 

  • Hemminki K, Li X (2004) Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br J Cancer 90:1765–1770

    CAS  PubMed  Google Scholar 

  • Henderson BE, Benton B, Jing J, Yu MC, Pike MC (1979) Risk factors for cancer of the testis in young men. Int J Cancer 23:598–602

    CAS  PubMed  Google Scholar 

  • Holmes L Jr, Escalante C, Garrison O, Foldi BX, Ogungbade GO, Essien EJ, Ward D (2008) Testicular cancer incidence trends in the USA (1975–2004): plateau or shifting racial paradigm? Public Health 122:862–872

    PubMed  Google Scholar 

  • Horner MJ RL, Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP, Stinchcomb DG, Edwards BK (eds) (2011) SEER cancer statistics review, 1975–2008. National Cancer Institute, Bethesda (Based on November 2010 SEER data submission, posted to the SEER web site, 2011)

    Google Scholar 

  • Horvath A, Korde L, Greene MH, Libe R, Osorio P, Faucz FR, Raffin-Sanson ML, Tsang KM, Drori-Herishanu L, Patronas Y, Remmers EF, Nikita ME, Moran J, Greene J, Nesterova M, Merino M, Bertherat J, Stratakis CA (2009) Functional phosphodiesterase 11A mutations may modify the risk of familial and bilateral testicular germ cell tumors. Cancer Res 69:5301–5306

    CAS  PubMed  Google Scholar 

  • Houldsworth J, Korkola JE, Bosl GJ, Chaganti RS (2006) Biology and genetics of adult male germ cell tumors. J Clin Oncol 24:5512–5518

    CAS  PubMed  Google Scholar 

  • Howe HL, Wu X, Ries LA, Cokkinides V, Ahmed F, Jemal A, Miller B, Williams M, Ward E, Wingo PA, Ramirez A, Edwards BK (2006) Annual report to the nation on the status of cancer, 1975–2003, featuring cancer among U.S. Hispanic/Latino populations. Cancer 107:1711–1742

    PubMed  Google Scholar 

  • Huddart SN, Mann JR, Gornall P, Pearson D, Barrett A, Raafat F, Barnes JM, Wallendsus KR (1990) The UK Children’s Cancer Study Group: testicular malignant germ cell tumours 1979–1988. J Pediatr Surg 25:406–410

    CAS  PubMed  Google Scholar 

  • Jacobsen R, Moller H, Thoresen SO, Pukkala E, Kjaer SK, Johansen C (2006) Trends in testicular cancer incidence in the Nordic countries, focusing on the recent decrease in Denmark. Int J Androl 29:199–204

    PubMed  Google Scholar 

  • Johnson KJ, Carozza SE, Chow EJ, Fox EE, Horel S, McLaughlin CC, Mueller BA, Puumala SE, Reynolds P, Von Behren J, Spector LG (2009a) Parental age and risk of childhood cancer: a pooled analysis. Epidemiology 20:475–483

    PubMed  Google Scholar 

  • Johnson KJ, Poynter JN, Ross JA, Robison LL, Shu XO (2009b) Pediatric germ cell tumors and maternal vitamin supplementation: a Children’s Oncology Group study. Cancer Epidemiol Biomarkers Prev 18:2661–2664

    PubMed  Google Scholar 

  • Johnson KJ, Ross JA, Poynter JN, Linabery AM, Robison LL, Shu XO (2009c) Paediatric germ cell tumours and congenital abnormalities: a Children’s Oncology Group study. Br J Cancer 101:518–521

    CAS  PubMed  Google Scholar 

  • Johnston HE, Mann JR, Williams J, Waterhouse JA, Birch JM, Cartwright RA, Draper GJ, Hartley AL, McKinney PA, Hopton PA et al (1986) The Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case–control study in children with germ cell tumours. Carcinogenesis 7:717–722

    CAS  PubMed  Google Scholar 

  • Kaijser M, Akre O, Cnattingius S, Ekbom A (2003) Maternal lung cancer and testicular cancer risk in the offspring. Cancer Epidemiol Biomarkers Prev 12:643–646

    PubMed  Google Scholar 

  • Kanetsky PA, Mitra N, Vardhanabhuti S, Li M, Vaughn DJ, Letrero R, Ciosek SL, Doody DR, Smith LM, Weaver J, Albano A, Chen C, Starr JR, Rader DJ, Godwin AK, Reilly MP, Hakonarson H, Schwartz SM, Nathanson KL (2009) Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet 41:811–815

    CAS  PubMed  Google Scholar 

  • Kanetsky PA, Mitra N, Vardhanabhuti S, Vaughn DJ, Li M, Ciosek SL, Letrero R, D’Andrea K, Vaddi M, Doody DR, Weaver J, Chen C, Starr JR, Hakonarson H, Rader DJ, Godwin AK, Reilly MP, Schwartz SM, Nathanson KL (2011) A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. Hum Mol Genet 20:3109–3117

    CAS  PubMed  Google Scholar 

  • Kratz CP, Han SS, Rosenberg PS, Berndt SI, Burdett L, Yeager M, Korde LA, Mai PL, Pfeiffer R, Greene MH (2011) Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. J Med Genet 48:473–476

    CAS  PubMed  Google Scholar 

  • Krege S, Beyer J, Souchon R, Albers P, Albrecht W, Algaba F, Bamberg M, Bodrogi I, Bokemeyer C, Cavallin-Stahl E, Classen J, Clemm C, Cohn-Cedermark G, Culine S, Daugaard G, De Mulder PH, De Santis M, de Wit M, de Wit R, Derigs HG, Dieckmann KP, Dieing A, Droz JP, Fenner M, Fizazi K, Flechon A, Fossa SD, del Muro XG, Gauler T, Geczi L, Gerl A, Germa-Lluch JR, Gillessen S, Hartmann JT, Hartmann M, Heidenreich A, Hoeltl W, Horwich A, Huddart R, Jewett M, Joffe J, Jones WG, Kisbenedek L, Klepp O, Kliesch S, Koehrmann KU, Kollmannsberger C, Kuczyk M, Laguna P, Galvis OL, Loy V, Mason MD, Mead GM, Mueller R, Nichols C, Nicolai N, Oliver T, Ondrus D, Oosterhof GO, Ares LP, Pizzocaro G, Pont J, Pottek T, Powles T, Rick O, Rosti G, Salvioni R, Scheiderbauer J, Schmelz HU, Schmidberger H, Schmoll HJ, Schrader M, Sedlmayer F, Skakkebaek NE, Sohaib A, Tjulandin S, Warde P, Weinknecht S, Weissbach L, Wittekind C, Winter E, Wood L, von der Maase H (2008) European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 53:478–496

    PubMed  Google Scholar 

  • Kroman N, Frisch M, Olsen JH, Westergaard T, Melbye M (1996) Oestrogen-related cancer risk in mothers of testicular-cancer patients. Int J Cancer 66:438–440

    CAS  PubMed  Google Scholar 

  • Kumar S, Shah JP, Bryant CS, Imudia AN, Cote ML, Ali-Fehmi R, Malone JM Jr, Morris RT (2008) The prevalence and prognostic impact of lymph node metastasis in malignant germ cell tumors of the ovary. Gynecol Oncol 110:125–132

    PubMed  Google Scholar 

  • Kuratsu J, Ushio Y (1996) Epidemiological study of primary intracranial tumors in childhood. A population-based survey in Kumamoto Prefecture, Japan. Pediatr Neurosurg 25:240–246; discussion 247

    CAS  PubMed  Google Scholar 

  • Lacerda HM, Akre O, Merletti F, Richiardi L (2009) Time trends in the incidence of testicular cancer in childhood and young adulthood. Cancer Epidemiol Biomarkers Prev 18:2042–2045

    PubMed  Google Scholar 

  • Lambrot R, Muczynski V, Lecureuil C, Angenard G, Coffigny H, Pairault C, Moison D, Frydman R, Habert R, Rouiller-Fabre V (2009) Phthalates impair germ cell development in the human fetal testis in vitro without change in testosterone production. Environ Health Perspect 117:32–37

    CAS  PubMed  Google Scholar 

  • Lapes M, Iozzi L, Ziegenfus WD, Antoniades K, Vivacqua R (1977) Familial testicular cancer in a father (bilateral seminoma-embryonal cell carcinoma) and son (teratocarcinoma): a case report and review of the literature. Cancer 39:2317–2320

    CAS  PubMed  Google Scholar 

  • Lerro CC, McGlynn KA, Cook MB (2010) A systematic review and meta-analysis of the relationship between body size and testicular cancer. Br J Cancer 103:1467–1474

    CAS  PubMed  Google Scholar 

  • Li FP, Fraumeni JF (1972) Testicular cancers in children: epidemiologic characteristics. J Natl Cancer Inst 48:1575–1581

    CAS  PubMed  Google Scholar 

  • Li YJ, Song TB, Cai YY, Zhou JS, Song X, Zhao X, Wu XL (2009) Bisphenol A exposure induces apoptosis and upregulation of Fas/FasL and caspase-3 expression in the testes of mice. Toxicol Sci 108:427–436

    CAS  PubMed  Google Scholar 

  • Liu S, Semenciw R, Waters C, Wen SW, Mery LS, Mao Y (2000) Clues to the aetiological heterogeneity of testicular seminomas and non-seminomas: time trends and age-period-cohort effects. Int J Epidemiol 29:826–831

    CAS  PubMed  Google Scholar 

  • Mann JR, Raafat F, Robinson K, Imeson J, Gornall P, Sokal M, Gray E, McKeever P, Hale J, Bailey S, Oakhill A (2000) The United Kingdom Children’s Cancer Study Group’s second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol 18:3809–3818

    CAS  PubMed  Google Scholar 

  • McGlynn KA (2001) Environmental and host factors in testicular germ cell tumors. Cancer Invest 19:842–853

    CAS  PubMed  Google Scholar 

  • McGlynn KA, Devesa SS, Graubard BI, Castle PE (2005) Increasing incidence of testicular germ cell tumors among black men in the United States. J Clin Oncol 23:5757–5761

    PubMed  Google Scholar 

  • McGlynn KA, Devesa SS, Sigurdson AJ, Brown LM, Tsao L, Tarone RE (2003) Trends in the incidence of testicular germ cell tumors in the United States. Cancer 97:63–70

    PubMed  Google Scholar 

  • McGlynn KA, Quraishi SM, Graubard BI, Weber JP, Rubertone MV, Erickson RL (2008) Persistent organochlorine pesticides and risk of testicular germ cell tumors. J Natl Cancer Inst 100:663–671

    CAS  PubMed  Google Scholar 

  • McGlynn KA, Quraishi SM, Graubard BI, Weber JP, Rubertone MV, Erickson RL (2009) Polychlorinated biphenyls and risk of testicular germ cell tumors. Cancer Res 69:1901–1909

    CAS  PubMed  Google Scholar 

  • McLachlan JA, Newbold RR, Bullock B (1975) Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science 190:991–992

    CAS  PubMed  Google Scholar 

  • Moller H (1993) Clues to the aetiology of testicular germ cell tumours from descriptive epidemiology. Eur Urol 23:8–13; discussion 14–15

    CAS  PubMed  Google Scholar 

  • Moller H, Evans H (2003) Epidemiology of gonadal germ cell cancer in males and females. Apmis 111:43–46; discussion 46–48

    PubMed  Google Scholar 

  • Moller H, Jorgensen N, Forman D (1995) Trends in incidence of testicular cancer in boys and adolescent men. Int J Cancer 61:761–764

    CAS  PubMed  Google Scholar 

  • Moller H, Skakkebaek NE (1997) Testicular cancer and cryptorchidism in relation to prenatal factors: case–control studies in Denmark. Cancer Causes Control 8:904–912

    CAS  PubMed  Google Scholar 

  • Moller H, Westergaard T (1998) Tobacco smoking and testicular cancer. Ugeskr Laeger 160:1041–1042

    CAS  PubMed  Google Scholar 

  • Moss AR, Osmond D, Bacchetti P, Torti FM, Gurgin V (1986) Hormonal risk factors in testicular cancer. A case–control study. Am J Epidemiol 124:39–52

    CAS  PubMed  Google Scholar 

  • Motta PM, Nottola SA, Makabe S (1997) Natural history of the female germ cell from its origin to full maturation through prenatal ovarian development. Eur J Obstet Gynecol Reprod Biol 75:5–10

    CAS  PubMed  Google Scholar 

  • Mukai M, Takamatsu H, Noguchi H, Tahara H (1998) Intra-abdominal testis with mature teratoma. Pediatr Surg Int 13:204–205

    CAS  PubMed  Google Scholar 

  • Musselman JR, Jurek AM, Johnson KJ, Linabery AM, Robison LL, Shu XO, Ross JA (2010) Maternal dietary patterns during early pregnancy and the odds of childhood germ cell tumors: a Children’s Oncology Group study. Am J Epidemiol 173:282–291

    PubMed  Google Scholar 

  • Narod SA, Hawkins MM, Robertson CM, Stiller CA (1997) Congenital anomalies and childhood cancer in Great Britain. Am J Hum Genet 60:474–485

    CAS  PubMed  Google Scholar 

  • Nathanson KL, Kanetsky PA, Hawes R, Vaughn DJ, Letrero R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Oosterhuis JW, Gillis AJ, Looijenga LH, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Rudd M, Huddart R, Crockford GP, Forman D, Oliver DT, Einhorn L, Weber BL, Kramer J, McMaster M, Greene MH, Pike M, Cortessis V, Chen C, Schwartz SM, Bishop DT, Easton DF, Stratton MR, Rapley EA (2005) The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am J Hum Genet 77:1034–1043

    CAS  PubMed  Google Scholar 

  • Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM et al (1994) Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371:75–80

    CAS  PubMed  Google Scholar 

  • Nishi M, Miyake H, Takeda T, Hatae Y (2000) Congenital malformations and childhood cancer. Med Pediatr Oncol 34:250–254

    CAS  PubMed  Google Scholar 

  • Oosterhuis JW, Looijenga LH (2005) Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer 5:210–222

    CAS  PubMed  Google Scholar 

  • Oosterhuis JW, Stoop H, Honecker F, Looijenga LH (2007) Why human extragonadal germ cell tumours occur in the midline of the body: old concepts, new perspectives. Int J Androl 30:256–263; discussion 263–264

    PubMed  Google Scholar 

  • Parkin DM, Kramarova E, Draper GJ, Masuyer E, Michaelis J, Neglia J, Qureshi S, Stiller CA (eds) (1998) International incidence of childhood cancer. International Agency for Research on Cancer/World Health Organization, Lyon

    Google Scholar 

  • Polednak AP (1996) Familial testicular cancer in a population-based cancer registry. Urol Int 56:238–240

    CAS  PubMed  Google Scholar 

  • Poynter JN, Amatruda JF, Ross JA (2010a) Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006. Cancer 116:4882–4891

    PubMed  Google Scholar 

  • Poynter JN, Hooten AJ, Frazier AL, Ross JA (2012) Associations between variants in KITLG, SPRY4, BAK1 and DMRT1 and pediatric germ cell tumors. Genes Chromosomes Cancer 51:266–271

    CAS  PubMed  Google Scholar 

  • Poynter JN, Radzom AH, Spector LG, Puumala S, Robison LL, Chen Z, Ross JA, Shu XO (2010b) Family history of cancer and malignant germ cell tumors in children: a report from the Children’s Oncology Group. Cancer Causes Control 21:181–189

    PubMed  Google Scholar 

  • Prener A, Engholm G, Jensen OM (1996) Genital anomalies and risk for testicular cancer in Danish men. Epidemiology 7:14–19

    CAS  PubMed  Google Scholar 

  • Purdue MP, Devesa SS, Sigurdson AJ, McGlynn KA (2005) International patterns and trends in testis cancer incidence. Int J Cancer 115:822–827

    CAS  PubMed  Google Scholar 

  • Purdue MP, Graubard BI, Chanock SJ, Rubertone MV, Erickson RL, McGlynn KA (2008) Genetic variation in the inhibin pathway and risk of testicular germ cell tumors. Cancer Res 68:3043–3048

    CAS  PubMed  Google Scholar 

  • Purdue MP, Sakoda LC, Graubard BI, Welch R, Chanock SJ, Sesterhenn IA, Rubertone MV, Erickson RL, McGlynn KA (2007) A case–control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors. Cancer Epidemiol Biomarkers Prev 16:77–83

    CAS  PubMed  Google Scholar 

  • Raman JD, Nobert CF, Goldstein M (2005) Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol 174:1819–1822; discussion 1822

    PubMed  Google Scholar 

  • Rankin J, Silf KA, Pearce MS, Parker L, Ward Platt M (2008) Congenital anomaly and childhood cancer: a population-based, record linkage study. Pediatr Blood Cancer 51:608–612

    PubMed  Google Scholar 

  • Rapley E (2007) Susceptibility alleles for testicular germ cell tumour: a review. Int J Androl 30:242–250; discussion 250

    CAS  PubMed  Google Scholar 

  • Rapley EA, Turnbull C, Al Olama AA, Dermitzakis ET, Linger R, Huddart RA, Renwick A, Hughes D, Hines S, Seal S, Morrison J, Nsengimana J, Deloukas P, Rahman N, Bishop DT, Easton DF, Stratton MR (2009) A genome-wide association study of testicular germ cell tumor. Nat Genet 41:807–810

    CAS  PubMed  Google Scholar 

  • Rescorla FJ, Breitfeld PP (1999) Pediatric germ cell tumors. Curr Probl Cancer 23:257–303

    CAS  PubMed  Google Scholar 

  • Richiardi L, Bellocco R, Adami HO, Torrang A, Barlow L, Hakulinen T, Rahu M, Stengrevics A, Storm H, Tretli S, Kurtinaitis J, Tyczynski JE, Akre O (2004) Testicular cancer incidence in eight northern European countries: secular and recent trends. Cancer Epidemiol Biomarkers Prev 13:2157–2166

    PubMed  Google Scholar 

  • Rodvall Y, Dich J, Wiklund K (2003) Cancer risk in offspring of male pesticide applicators in agriculture in Sweden. Occup Environ Med 60:798–801

    CAS  PubMed  Google Scholar 

  • Rosen A, Jayram G, Drazer M, Eggener SE (2011) Global trends in testicular cancer incidence and mortality. Eur Urol 60:374–379

    PubMed  Google Scholar 

  • Sarma A, McLaughlin J, Schottenfeld D (2006) Testicular cancer. In: Schottenfeld D, Fraumeni JE Jr (eds) Cancer epidemiology and prevention, 3rd edn. Oxford University Press, New York, pp 1159–1160

    Google Scholar 

  • Schottenfeld D (1996) Testicular cancer. In: Schottenfeld D, Fraumeni JE Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, New York, pp 1207–1219

    Google Scholar 

  • Schottenfeld D, Warshauer ME, Sherlock S, Zauber AG, Leder M, Payne R (1980) The epidemiology of testicular cancer in young adults. Am J Epidemiol 112:232–246

    CAS  PubMed  Google Scholar 

  • Shah JP, Kumar S, Bryant CS, Ali-Fehmi R, Malone JM Jr, Deppe G, Morris RT (2008) A population-based analysis of 788 cases of yolk sac tumors: a comparison of males and females. Int J Cancer 123:2671–2675

    CAS  PubMed  Google Scholar 

  • Shah MN, Devesa SS, Zhu K, McGlynn KA (2007) Trends in testicular germ cell tumours by ethnic group in the United States. Int J Androl 30:206–213; discussion 213–214

    PubMed  Google Scholar 

  • Shankar S, Davies S, Giller R, Krailo M, Davis M, Gardner K, Cai H, Robison L, Shu XO (2006) In utero exposure to female hormones and germ cell tumors in children. Cancer 106:1169–1177

    PubMed  Google Scholar 

  • Shu XO, Nesbit ME, Buckley JD, Krailo MD, Robinson LL (1995) An exploratory analysis of risk factors for childhood malignant germ-cell tumors: report from the Childrens Cancer Group (Canada, United States). Cancer Causes Control 6:187–198

    CAS  PubMed  Google Scholar 

  • Shulman LP, Muram D, Marina N, Jones C, Portera JC, Wachtel SS, Simpson JL, Elias S (1994) Lack of heritability in ovarian germ cell malignancies. Am J Obstet Gynecol 170:1803–1805; discussion 1805–1808

    CAS  PubMed  Google Scholar 

  • Skakkebaek NE, Holm M, Hoei-Hansen C, Jorgensen N, Rajpert-De Meyts E (2003) Association between testicular dysgenesis syndrome (TDS) and testicular neoplasia: evidence from 20 adult patients with signs of maldevelopment of the testis. APMIS 111:1–9; discussion 9–11

    PubMed  Google Scholar 

  • Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16:972–978

    CAS  PubMed  Google Scholar 

  • Smith HO, Berwick M, Verschraegen CF, Wiggins C, Lansing L, Muller CY, Qualls CR (2006) Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol 107:1075–1085

    PubMed  Google Scholar 

  • Sonneveld DJ, Sleijfer DT, Schrafford Koops H, Sijmons RH, van der Graaf WT, Sluiter WJ, Hoekstra HJ (1999) Familial testicular cancer in a single-centre population. Eur J Cancer 35:1368–1373

    CAS  PubMed  Google Scholar 

  • Spermon JR, Witjes JA, Nap M, Kiemeney LA (2001) Cancer incidence in relatives of patients with testicular cancer in the eastern part of The Netherlands. Urology 57:747–752

    CAS  PubMed  Google Scholar 

  • Starr JR, Chen C, Doody DR, Hsu L, Ricks S, Weiss NS, Schwartz SM (2005) Risk of testicular germ cell cancer in relation to variation in maternal and offspring cytochrome p450 genes involved in catechol estrogen metabolism. Cancer Epidemiol Biomarkers Prev 14:2183–2190

    CAS  PubMed  Google Scholar 

  • Stephansson O, Wahnstrom C, Pettersson A, Sorensen HT, Tretli S, Gissler M, Troisi R, Akre O, Grotmol T (2011) Perinatal risk factors for childhood testicular germ-cell cancer: a Nordic population-based study. Cancer Epidemiol 35:e100–e104

    PubMed  Google Scholar 

  • Sun M, Abdollah F, Liberman D, Abdo A, Thuret R, Tian Z, Shariat SF, Montorsi F, Perrotte P, Karakiewicz PI (2011) Racial disparities and socioeconomic status in men diagnosed with testicular germ cell tumors: a survival analysis. Cancer 117:4277–4285

    PubMed  Google Scholar 

  • Swerdlow AJ, Huttly SR, Smith PG (1987) Prenatal and familial associations of testicular cancer. Br J Cancer 55:571–577

    CAS  PubMed  Google Scholar 

  • Swerdlow AJ, Stiller CA, Wilson LM (1982) Prenatal factors in the aetiology of testicular cancer: an epidemiological study of childhood testicular cancer deaths in Great Britain, 1953–73. J Epidemiol Community Health 36:96–101

    CAS  PubMed  Google Scholar 

  • Toriola AT, Surcel HM, Lundin E, Schock H, Grankvist K, Pukkala E, Chen T, Toniolo P, Lehtinen M, Zeleniuch-Jacquotte A, Lukanova A (2011) Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case–control study. Cancer Causes Control 22:1607–1611

    PubMed  Google Scholar 

  • Turnbull C, Rapley EA, Seal S, Pernet D, Renwick A, Hughes D, Ricketts M, Linger R, Nsengimana J, Deloukas P, Huddart RA, Bishop DT, Easton DF, Stratton MR, Rahman N (2010) Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet 42:604–607

    CAS  PubMed  Google Scholar 

  • United Kingdom Testicular Cancer Study Group (1994) Aetiology of testicular cancer: association with congenital abnormalities, age at puberty, infertility, and exercise. BMJ 308:1393–1399

    Google Scholar 

  • Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8:755–768

    CAS  PubMed  Google Scholar 

  • Von Behren J, Spector LG, Mueller BA, Carozza SE, Chow EJ, Fox EE, Horel S, Johnson KJ, McLaughlin C, Puumala SE, Ross JA, Reynolds P (2011) Birth order and risk of childhood cancer: a pooled analysis from five US States. Int J Cancer 128:2709–2716

    Google Scholar 

  • Walker AH, Ross RK, Haile RW, Henderson BE (1988) Hormonal factors and risk of ovarian germ cell cancer in young women. Br J Cancer 57:418–422

    CAS  PubMed  Google Scholar 

  • Walsh TJ, Dall’Era MA, Croughan MS, Carroll PR, Turek PJ (2007) Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer. J Urol 178:1440–1446; discussion 1446

    PubMed  Google Scholar 

  • Walsh TJ, Davies BJ, Croughan MS, Carroll PR, Turek PJ (2008) Racial differences among boys with testicular germ cell tumors in the United States. J Urol 179:1961–1965

    PubMed  Google Scholar 

  • Walsh TJ, Grady RW, Porter MP, Lin DW, Weiss NS (2006) Incidence of testicular germ cell cancers in U.S. children: SEER program experience 1973 to 2000. Urology 68:402–405; discussion 405

    PubMed  Google Scholar 

  • Wanderas EH, Grotmol T, Fossa SD, Tretli S (1998) Maternal health and pre- and perinatal characteristics in the etiology of testicular cancer: a prospective population- and register-based study on Norwegian males born between 1967 and 1995. Cancer Causes Control 9:475–486

    CAS  PubMed  Google Scholar 

  • Weir HK, Marrett LD, Kreiger N, Darlington GA, Sugar L (2000) Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer. Int J Cancer 87:438–443

    CAS  PubMed  Google Scholar 

  • Weir HK, Marrett LD, Moravan V (1999) Trends in the incidence of testicular germ cell cancer in Ontario by histologic subgroup, 1964–1996. Cmaj 160:201–205

    CAS  PubMed  Google Scholar 

  • Weiss NS, Cook LS, Farrow DC, Rosenblatt KA (1996) Ovarian cancer. In: Schottenfeld D, Fraumeni JE Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, New York, pp 1040–1057

    Google Scholar 

  • Westergaard T, Olsen JH, Frisch M, Kroman N, Nielsen JW, Melbye M (1996) Cancer risk in fathers and brothers of testicular cancer patients in Denmark. A population-based study. Int J Cancer 66:627–631

    CAS  PubMed  Google Scholar 

  • Westhoff C, Pike M, Vessey M (1988) Benign ovarian teratomas: a population-based case–control study. Br J Cancer 58:93–98

    CAS  PubMed  Google Scholar 

  • Wilhelm D, Palmer S, Koopman P (2007) Sex determination and gonadal development in mammals. Physiol Rev 87:1–28

    CAS  PubMed  Google Scholar 

  • Wilkinson JD, Gonzalez A, Wohler-Torres B, Fleming LE, MacKinnon J, Trapido E, Button J, Peace S (2005) Cancer incidence among Hispanic children in the United States. Rev Panam Salud Publica 18:5–13

    PubMed  Google Scholar 

  • Wong TT, Ho DM, Chang KP, Yen SH, Guo WY, Chang FC, Liang ML, Pan HC, Chung WY (2005) Primary pediatric brain tumors: statistics of Taipei VGH, Taiwan (1975–2004). Cancer 104:2156–2167

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the Children’s Cancer Research Fund, Minneapolis, MN.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Jenny N. Poynter

Authors
  1. Jenny N. Poynter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jenny N. Poynter .

Editor information

Editors and Affiliations

  1. Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    A. Lindsay Frazier

  2. Dept. of Pediatrics, MolecularBiology an, UT Southewestern Medical Center, Dallas, Texas, USA

    James F. Amatruda

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Poynter, J.N. (2014). Epidemiology of Germ Cell Tumors. In: Frazier, A., Amatruda, J. (eds) Pediatric Germ Cell Tumors. Pediatric Oncology, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38971-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-38971-9_2

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-38970-2

  • Online ISBN: 978-3-642-38971-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation