Cancer Causes & Control

, Volume 3, Issue 3, pp 265–272 | Cite as

Birth order and risk of testicular cancer

  • Anne Prener
  • Chung-cheng Hsieh
  • Gerda Engholm
  • Dimitrios Trichopoulos
  • Ole M. Jensen
Research Papers


To explore the etiology of testicular cancer, cases of testicular cancer were identified among members of a cobort of Danish boys born between 1941 and 1957 (inclusive), who had attended schools in Copenhagen and Gentofte and whose school health records were contained in an archive under the supervision of the Danish Cancer Registry. One hundred and eighty-three cases of testicular cancer diagnosed before 31 December 1984 were identified; 366 controls, matched to cases by sex and age, were selected from the same cohort. Information on potential risk factors and confounders was obtained from two sources: school health records and midwife protocols, both of which were recorded prior to the diagnosis of testicular cancer in cases. Relative risks (RR) approximated by the odds ratios were calculated and, in logistic regression analyses, adjustments were done for known or suspected confounders. A decreasing risk of testicular cancer with increasing birth order was observed (P=0.020). Compared with being firstborn, being number four or more in birth order was associated with a significantly decreased RR for all testicular cancers (RR=0.3,95 percent confidence interval [CI]=0.3–0.8) and testicular seminoma (RR=0.1, CI=0.02–0.9). No association was observed between high social class and the risk of testicular cancer (RR=1.4, CI=0.8–2.3); neither was age at which the study subjects had mumps or measles related to risk of testicular cancer. No cases of mumps orchitis were observed before or during school years. A slightly increased RR for testicular cancer among boys from small families could be explained by the association between family size and birth order. The observed association between rank in birth order and the risk of testicular cancer was attributed to the reported differences in maternal estrogen levels in first cf second pregnancy, and supports the hypothesis of a tumor-initializing effect of high levels of estrogen early in a pregnancy on the developing testicular tissues.

Key words

Birth order Denmark risk factors testicular cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Muir C, Waterhouse J, Mack T, Powell J, Whelan S, eds. Cancer Incidence in Five Continents. Volume V. Lyon, France: International Agency for Research on Cancer, 1987; IARC Sci. Pub. No. 88.Google Scholar
  2. 2.
    Østerlind A. Diverging trends in incidence and mortality of testicular cancer in Denmark 1943–1982. Br J Cancer 1986; 53: 501–5.Google Scholar
  3. 3.
    Clemmesen J. Statistical studies in the aetiology of malignant neoplasms, Vol III. Acta Pathol Microbiol Scand 1969; Suppl209: XV-XLIII.Google Scholar
  4. 4.
    Henderson BE, Benton B, Jing J, Ya MC, Pike MC. Risk factors for cancer of the testis in young men. Int J Cancer 1979; 23: 598–602.Google Scholar
  5. 5.
    Schottenfeld D, Warshauer ME, Sherlock S, Zauber AG, Leder M, Payne R. The epidemiology of testicular cancer in young adults. Am J Epidemiol 1980; 112: 232–46.Google Scholar
  6. 6.
    Depue RH, Pike MC, Henderson BE. Estrogen exposure during gestation and risk of testicular cancer. JNCI 1983; 71: 1151–5.Google Scholar
  7. 7.
    Brown LM, Pottern LM, Hoover RN. Prenatal and perinatal risk factors for testicular cancer. Cancer Res 1986; 46: 4812–6.Google Scholar
  8. 8.
    Moss AR, Osmond D, Bacchetti P, Torti PM, Gurgin V. Hormonal risk factors in testicular cancer. A case-control study. Am J Epidemiol 1986; 124: 39–52.Google Scholar
  9. 9.
    Gershmann ST, Stolley PD. A case-control study of testicular cancer using Connecticut Tumour registry data. Int J Epidemiol 1988; 17: 738–42.Google Scholar
  10. 10.
    Bernstein L, Depue RH, Ross RK, Judd HL, Pike MC, Henderson BE. Higher maternal levels of free estradiol in first compared to second pregnancy: early gestational differences. JNCI 1986; 76: 1035–9.Google Scholar
  11. 11.
    Panagiotopoulou K, Katsouyanni K, Petridou E, Garas Y, Tzonou A, Trichopoulos D. Maternal age, parity and pregnancy estrogens. Cancer Causes Control 1990; 1: 119–24.Google Scholar
  12. 12.
    Østerlind A, Jensen OM. Evaluation of cancer registration in Denmark 1977. Ugeskr Lœg 1985; 147: 2483–5. (In Danish with English summary).Google Scholar
  13. 13.
    Fleiss JL. Statistical Methods for Rates and Proportions. New York: Wiley, 1981: 24–6, 61–71, 160–5.Google Scholar
  14. 14.
    Miettinen OS. Estimability and estimation in case-referent studies. Am J Epidemiol 1976; 103: 226–35.Google Scholar
  15. 15.
    Mantel N. Chi-square tests with one degree of freedom: extensions of the Mantel-Haenszel procedure. J Am Stat Assoc 1963; 58: 690–700.Google Scholar
  16. 16.
    Breslow NE, Day NE. Statistical Methods in Cancer Research. Vol 1. The Analysis of Case-control Studies. Lyon, France: International Agency for Research on Cancer, 1980; IARC Sci. Pub. No. 32.Google Scholar
  17. 17.
    Statistics and Epidemiology Research Corporation and Cytel Software Corporation. EGRET Reference Manual (First draft). Seattle, NA: SERC, Inc. 1990.Google Scholar
  18. 18.
    Swerdlow AJ, Huttly SRA, Smith PG. Prenatal and familial associations of testicular cancer. Br J Cancer 1987; 55: 571–7.Google Scholar
  19. 19.
    Beard CM, Benson RC, Kelalia PP, Elvebach LR, Kurland LT. The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc 1977; 52: 3–7.Google Scholar
  20. 20.
    Swerdlow AJ, Huttly SRA, Smith PG. Testicular cancer and antecedent diseases. Br J Cancer 1987; 55: 97–103.Google Scholar
  21. 21.
    Morrison AS. Some social and medical characteristics of army men with testicular cancer. Am J Epidemiol 1976; 104: 511–6.Google Scholar
  22. 22.
    Loughlin JE, Robbey SJ, Morrison AS, Risk factors for cancer of the testis. New Engl J Med 1980; 303: 112–3.Google Scholar
  23. 23.
    Coldman AJ, Elwood JM, Gallagher RI. Br J Cancer 1982; 46: 749–56.Google Scholar
  24. 24.
    Brown LM, Pottern LM, Hoover RN. Testicular cancer in young men: the search for causes of the epidemic increase in the United States. J Epidemiol Commun Health 1987; 41: 349–54.Google Scholar
  25. 25.
    Horwitz O, Grünfeld K, Lysgaard-Hansen B, Kjeldsen K. The epidemiology and natural history of measles in Denmark. Am J Epidemiol 1974; 100: 136–49.Google Scholar
  26. 26.
    Algood CB, Newell GR, Johnson DE. Viral etiology of testicular tumors. J Urol 1988; 139: 308–10.Google Scholar
  27. 27.
    Mueller N, Hinkula J, Wahren B. Elevated antibody titers against cytomegalovirus among patients with testicular cancer. Int J Cancer 1988; 41: 399–403.Google Scholar
  28. 28.
    International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall Evaluation of Carcinogenicity: an Updating of IARC Monographs, Volumes 1 to 42. Suppl. 7. Lyon, France: International Agency for Research on Cancer, 1987: 272.Google Scholar
  29. 29.
    Gilbert JB, Hamilton JB. Studies in malignant testis tumours. III. Incidence and nature of tumours in ectopic testis. Surg Gynecol Obstet 1940; 71: 731–43.Google Scholar
  30. 30.
    Morrison AS, Cryptorchidism, hernia and cancer of the testis. JNCI 1976; 56: 731–3.Google Scholar
  31. 31.
    Pottern LM, Brown LM, Hoover RN, et al. Testicular cancer risk among young men: role of cryptorchidism and inguinal hernia. JNCI 1985; 74: 377–81.Google Scholar
  32. 32.
    Giwercman A, Bruun E, Frimodt-M∅ller C, Skakkebæk NE. Incidence of carcinoma-in-situ of the testis in men with a history of cryptorchidism. J Urol 1989: 142: 998–1001.Google Scholar
  33. 33.
    Strader CH, Weiss NS, Daling JR, Karagas MR, Malenight B. Cryptorchidism, orchiopexy and the risk of testicular cancer. Am J Epidemiol 1988; 127: 1013–8.Google Scholar
  34. 34.
    Haughey BP, Graham S, Brasure J, Zielezny M, Sufrin G, Burnett WS. The epidemiology of testicular cancer in upstate New York. Am J Epidemiol 1989; 130: 25–36.Google Scholar
  35. 35.
    Bernstein L, Pike MC, Depue RH, Ross RK, Moore JW, Henderson BE. Maternal hormonal levels in early gestation of cryptorchid males: a case-control study. Br J Cancer 1988; 58: 379–81.Google Scholar
  36. 36.
    McLachlan JA, Nearbold RR, Bullock B. Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science 1975; 190: 991.Google Scholar
  37. 37.
    Walker AH, Bernstein L, Warren DW, Warner NE, Zheng X, Henderson BE. The effect of in-utero ethinyloestradiol exposure on the risk of cryptorchid testis and testicular teratoma in mice. Br J Cancer 1990; 62: 559–602.Google Scholar
  38. 38.
    Herbst A, Ulfelder H, Poskanzer D. Adenocarcinoma of the vagina. N Engl J Med 1971: 284: 878.Google Scholar
  39. 39.
    Gill WB, Schumacher GFB, Bibbo M, Straus FHII, Schoenberg HW. Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and severe abnormalities. J Urol 1979; 122: 36–9.Google Scholar
  40. 40.
    Carstens B, Clemmesen J. Genital tract cancers in Danish adolescents. New Engl J Med 1972; 287: 198.Google Scholar
  41. 41.
    Danish Statistical Bureau. Marriages, Births and Deaths 1956–1969. Statistical Tables 1973: XI. Copenhagen: Danish Statistical Bureau, The Statistical Bureau, 1973. (In Danish).Google Scholar
  42. 42.
    Whittemore AS, Paffenbarger RSJr, Anderson K, Lee JE. Early precursors of urogenital cancers in former college men. J Urol 1984; 132: 1256–61.Google Scholar
  43. 43.
    Nethersell ABW, Sikora K. Testicular cancer and social class in East Anglia. Br J Cancer 1984; 50: 537–40.Google Scholar
  44. 44.
    Mustacchi P, Millmore D. Racial and occupational variations in cancer of the testis: San Francisco, 1956–65. JNCI 1976; 56: 717–20.Google Scholar
  45. 45.
    Ross RK, McCurtis JW, Henderson BE, Menck HR, Mack TM, Martin SP. Descriptive epidemiology of testicular and prostatic cancer in Los Angeles. Br J Cancer 1979; 39: 284–92.Google Scholar
  46. 46.
    Davies TW, Prener A, Engholm G. Body size and cancer of the testis. Acta Oncol 1990; 3: 287–90.Google Scholar
  47. 47.
    Danish Statistical Bureau. Marriages, Births and Deaths 1941–1955. Statistical Tables 1962: I. Copenhagen: Danish Statistical Bureau, The Statistical Bureau, 1962. (In Danish).Google Scholar

Copyright information

© Rapid Communications of Oxford Ltd 1992

Authors and Affiliations

  • Anne Prener
    • 1
  • Chung-cheng Hsieh
    • 2
  • Gerda Engholm
    • 1
  • Dimitrios Trichopoulos
    • 2
  • Ole M. Jensen
  1. 1.Danish Cancer RegistryCopenhagenDenmark
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA

Personalised recommendations