Cancer Causes & Control

, Volume 21, Issue 2, pp 181–189 | Cite as

Family history of cancer and malignant germ cell tumors in children: A report from the Children’s Oncology Group

  • Jenny N. Poynter
  • Amy H. Radzom
  • Logan G. Spector
  • Susan Puumala
  • Leslie L. Robison
  • Zhi Chen
  • Julie A. Ross
  • Xiao-Ou Shu
Original paper


Family history of testicular cancer is an established risk factor for adult testicular germ cell tumors (GCT). We evaluated the association between family history of cancer and pediatric GCT in a Children’s Oncology Group case–control study that included 274 GCT cases (195 female and 79 male) diagnosed <age 15 years and 418 controls frequency matched to cases on sex and age. Family history data were collected through telephone interviews with biological mothers and fathers and unconditional logistic regression was used to evaluate associations with GCT adjusting for potential confounders. A family history of cancer with onset <age 40 years was associated with a reduced risk of GCT among female cases (Odds Ratio (OR) = 0.50, 95% Confidence Interval (CI) 0.28–0.89) and an increased risk among male cases (OR = 2.56, 95% CI 1.02–6.44). Male cases were more likely to report family history of melanoma compared with male controls (OR = 4.65, 95% CI 1.40–15.4). There was an inverse association between family history of ovarian or uterine cancers and GCT in girls (OR = 0.46, 95% CI 0.22–0.96). These sex and cancer site specific associations should be confirmed in additional studies as they may provide clues to the etiology of pediatric GCT.


Germ cell tumor Family history Children 



We would like to thank Michelle Roesler for assisting with the study database. We would also like to thank the study participants who have generously donated their time for this project. This research was supported by National Institutes of Health Grants R01 CA27623 and U10 CA98543 and the Children’s Cancer Research Fund, Minneapolis, MN


  1. 1.
    SEER cancer Statistics Review, 1975–2005 []
  2. 2.
    Ulbright TM (2005) Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol 18(Suppl 2):S61–S79CrossRefPubMedGoogle Scholar
  3. 3.
    Swerdlow AJ, Huttly SR, Smith PG (1987) Prenatal and familial associations of testicular cancer. Br J Cancer 55:571–577PubMedGoogle Scholar
  4. 4.
    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 7:717–722CrossRefPubMedGoogle Scholar
  5. 5.
    Walker AH, Ross RK, Haile RW, Henderson BE (1988) Hormonal factors and risk of ovarian germ cell cancer in young women. Br J Cancer 57:418–422PubMedGoogle Scholar
  6. 6.
    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 6:187–198CrossRefPubMedGoogle Scholar
  7. 7.
    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 134:273–281PubMedGoogle Scholar
  8. 8.
    Chen Z, Stewart PA, Davies S, Giller R, Krailo M, Davis M, Robison L, Shu XO (2005) Parental occupational exposure to pesticides and childhood germ-cell tumors. Am J Epidemiol 162:858–867CrossRefPubMedGoogle Scholar
  9. 9.
    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 209:31–40CrossRefPubMedGoogle Scholar
  10. 10.
    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 106:1169–1177CrossRefPubMedGoogle Scholar
  11. 11.
    Chen Z, Robison L, Giller R, Krailo M, Davis M, Gardner K, Davies S, Shu XO (2005) Risk of childhood germ cell tumors in association with parental smoking and drinking. Cancer 103:1064–1071CrossRefPubMedGoogle Scholar
  12. 12.
    Schottenfeld D (1996) Testicular cancer. In: Schottenfeld D, Fraumeni JE Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, New York, pp 1207–1219Google Scholar
  13. 13.
    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 1040–1057Google Scholar
  14. 14.
    dos Santos Silva I, Swerdlow AJ (1991) Ovarian germ cell malignancies in England: epidemiological parallels with testicular cancer. Br J Cancer 63:814–818PubMedGoogle Scholar
  15. 15.
    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 65:255–262PubMedGoogle Scholar
  16. 16.
    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 35:1368–1373CrossRefPubMedGoogle Scholar
  17. 17.
    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 66:627–631CrossRefPubMedGoogle Scholar
  18. 18.
    Heimdal K, Olsson H, Tretli S, Flodgren P, Borresen AL, Fossa SD (1996) Familial testicular cancer in Norway and southern Sweden. Br J Cancer 73:964–969PubMedGoogle Scholar
  19. 19.
    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 13:1316–1324PubMedGoogle Scholar
  20. 20.
    Moss AR, Osmond D, Bacchetti P, Torti FM, Gurgin V (1986) Hormonal risk factors in testicular cancer. A case–control study. Am J Epidemiol 124:39–52PubMedGoogle Scholar
  21. 21.
    Kroman N, Frisch M, Olsen JH, Westergaard T, Melbye M (1996) Oestrogen-related cancer risk in mothers of testicular-cancer patients. Int J Cancer 66:438–440CrossRefPubMedGoogle Scholar
  22. 22.
    Heimdal K, Olsson H, Tretli S, Flodgren P, Borresen AL, Fossa SD (1996) Risk of cancer in relatives of testicular cancer patients. Br J Cancer 73:970–973PubMedGoogle Scholar
  23. 23.
    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 57:747–752CrossRefPubMedGoogle Scholar
  24. 24.
    Kaijser M, Akre O, Cnattingius S, Ekbom A (2003) Maternal lung cancer and testicular cancer risk in the offspring. Cancer Epidemiol Biomarkers Prev 12:643–646PubMedGoogle Scholar
  25. 25.
    Hemminki K, Li X (2004) Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br J Cancer 90:1765–1770CrossRefPubMedGoogle Scholar
  26. 26.
    Hemminki K, Chen B (2006) Familial risks in testicular cancer as aetiological clues. Int J Androl 29:205–210CrossRefPubMedGoogle Scholar
  27. 27.
    Robison LL, Daigle A (1984) Control selection using random digit dialing for cases of childhood cancer. Am J Epidemiol 120:164–166PubMedGoogle Scholar
  28. 28.
    Waksberg J (1978) Sampling methods for random digit dialing. J Am Stat Assoc 73:40–46CrossRefGoogle Scholar
  29. 29.
    International Classification of Diseases, Ninth Revision, Clinical Modification []
  30. 30.
    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 1805–1808PubMedGoogle Scholar
  31. 31.
    Stettner AR, Hartenbach EM, Schink JC, Huddart R, Becker J, Pauli R, Long R, Laxova R (1999) Familial ovarian germ cell cancer: report and review. Am J Med Genet 84:43–46CrossRefPubMedGoogle Scholar
  32. 32.
    Huddart RA, Thompson C, Houlston R, Nicholls EJ, Horwich A (1996) Familial predisposition to both male and female germ cell tumours? J Med Genet 33:86CrossRefPubMedGoogle Scholar
  33. 33.
    Galani E, Alamanis C, Dimopoulos MA (2005) Familial female and male germ cell cancer. A new syndrome? Gynecol Oncol 96:254–255CrossRefPubMedGoogle Scholar
  34. 34.
    Airewele G, Adatto P, Cunningham J, Mastromarino C, Spencer C, Sharp M, Sigurdson A, Bondy M (1998) Family history of cancer in patients with glioma: a validation study of accuracy. J Natl Cancer Inst 90:543–544CrossRefPubMedGoogle Scholar
  35. 35.
    Kerber RA, Slattery ML (1997) Comparison of self-reported and database-linked family history of cancer data in a case–control study. Am J Epidemiol 146:244–248PubMedGoogle Scholar
  36. 36.
    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 39:2317–2320CrossRefPubMedGoogle Scholar
  37. 37.
    Polednak AP (1996) Familial testicular cancer in a population-based cancer registry. Urol Int 56:238–240PubMedCrossRefGoogle Scholar
  38. 38.
    Dieckmann KP, Pichlmeier U (1997) The prevalence of familial testicular cancer: an analysis of two patient populations and a review of the literature. Cancer 80:1954–1960CrossRefPubMedGoogle Scholar
  39. 39.
    Larson AA, Leachman SA, Eliason MJ, Cannon-Albright LA (2007) Population-based assessment of non-melanoma cancer risk in relatives of cutaneous melanoma probands. J Invest Dermatol 127:183–188CrossRefPubMedGoogle Scholar
  40. 40.
    Lens M, Bataille V (2008) Melanoma in relation to reproductive and hormonal factors in women: current review on controversial issues. Cancer Causes Control 19:437–442CrossRefPubMedGoogle Scholar
  41. 41.
    Henderson BE, Benton B, Jing J, Yu MC, Pike MC (1979) Risk factors for cancer of the testis in young men. Int J Cancer 23:598–602CrossRefPubMedGoogle Scholar
  42. 42.
    Schottenfeld D, Warshauer ME, Sherlock S, Zauber AG, Leder M, Payne R (1980) The epidemiology of testicular cancer in young adults. Am J Epidemiol 112:232–246PubMedGoogle Scholar
  43. 43.
    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 87:438–443CrossRefPubMedGoogle Scholar
  44. 44.
    Love RR, Evans AM, Josten DM (1985) The accuracy of patient reports of a family history of cancer. J Chronic Dis 38:289–293CrossRefPubMedGoogle Scholar
  45. 45.
    Ziogas A, Anton-Culver H (2003) Validation of family history data in cancer family registries. Am J Prev Med 24:190–198CrossRefPubMedGoogle Scholar
  46. 46.
    Murff HJ, Spigel DR, Syngal S (2004) Does this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history. JAMA 292:1480–1489CrossRefPubMedGoogle Scholar
  47. 47.
    Pinsky PF, Kramer BS, Reding D, Buys S (2003) Reported family history of cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Epidemiol 157:792–799CrossRefPubMedGoogle Scholar
  48. 48.
    Weinstock MA, Brodsky GL (1998) Bias in the assessment of family history of melanoma and its association with dysplastic nevi in a case–control study. J Clin Epidemiol 51:1299–1303CrossRefPubMedGoogle Scholar
  49. 49.
    Mitchell RJ, Brewster D, Campbell H, Porteous ME, Wyllie AH, Bird CC, Dunlop MG (2004) Accuracy of reporting of family history of colorectal cancer. Gut 53:291–295CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jenny N. Poynter
    • 1
  • Amy H. Radzom
    • 1
  • Logan G. Spector
    • 1
  • Susan Puumala
    • 1
  • Leslie L. Robison
    • 2
  • Zhi Chen
    • 3
  • Julie A. Ross
    • 1
  • Xiao-Ou Shu
    • 3
  1. 1.Department of Pediatrics, Division of Pediatric Epidemiology and Clinical ResearchUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of Epidemiology and Cancer ControlSt. Jude Children’s Research HospitalMemphisUSA
  3. 3.Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer CenterVanderbilt UniversityNashvilleUSA

Personalised recommendations