Skip to main content
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1986 Sep-Oct;59(5):547–559.

Multiple primary cancers in Denmark 1943-80; influence of possible underreporting and suggested risk factors.

H H Storm, E Lynge, A Osterlind, O M Jensen
PMCID: PMC2590183  PMID: 3798972

Abstract

The risk of developing a second primary cancer was studied among 171,749 men and 208,192 women who were reported to the Danish Cancer Registry between 1943 and 1980. Only those who survived at least two months were included in the analysis, and more than 1.7 million person-years of observation were accrued. Altogether, 15,084 second primary cancers developed, of which 13,231 were in organs other than the initial or adjacent site [relative risk (RR) = 1.01]. Adjustment for possible underreporting of multiple primary cancers increased the RR to 1.24, which stresses the need for detailed knowledge of registration procedures interpreting results from cancer registries. The unadjusted RR for all sites increased with time, from 0.94 during the first decade of follow-up (excluding the first year) to 1.13 among 30-year survivors, whereas the adjusted RR increased from 1.08 to 1.41. Elevated risks were observed for sites thought to have a common etiology. For example, cancers of smoking-related sites were increased in both directions following cancers of the oral cavity, respiratory tract, and urinary organs. For cancers suspected to have a hormone- or dietary fat-related association, significant reciprocal relationships were seen among cancers of the endometrium, ovary, and colon. Cancer treatment probably is an important factor in second cancer development, even when judged indirectly in the present study. For example, radiotherapy may have been responsible for an elevated risk of subsequent cancers of the thyroid, breast, colon, rectum, bladder, and connective tissue in long-term survivors. Chemotherapy may have increased the risk of subsequent leukemias. Our data further indicate that cancer patients have no general susceptibility to develop new malignant tumors, although high rates may be found for particular sites sharing common risk factors. Conversely, the occurrence of one cancer does not appear to protect against developing a new cancer.

Full text

PDF
559

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beebe G. W., Kato H., Land C. E. Studies of the mortality of A-bomb survivors: 6. mortality and radiation dose, 1950--1974. Radiat Res. 1978 Jul;75(1):138–201. [PubMed] [Google Scholar]
  2. Berg J. W., Hutter R. V., Foote F. W., Jr The unique association between salivary gland cancer and breast cancer. JAMA. 1968 May 27;204(9):771–774. [PubMed] [Google Scholar]
  3. Bibbo M., Haenszel W. M., Wied G. L., Hubby M., Herbst A. L. A twenty-five-year follow-up study of women exposed to diethylstilbestrol during pregnancy. N Engl J Med. 1978 Apr 6;298(14):763–767. doi: 10.1056/NEJM197804062981403. [DOI] [PubMed] [Google Scholar]
  4. Boice J. D., Jr, Storm H. H., Curtis R. E., Jensen O. M., Kleinerman R. A., Jensen H. S., Flannery J. T., Fraumeni J. F., Jr Introduction to the study of multiple primary cancers. Natl Cancer Inst Monogr. 1985 Dec;68:3–9. [PubMed] [Google Scholar]
  5. Brinton L. A., Blot W. J., Becker J. A., Winn D. M., Browder J. P., Farmer J. C., Jr, Fraumeni J. F., Jr A case-control study of cancers of the nasal cavity and paranasal sinuses. Am J Epidemiol. 1984 Jun;119(6):896–906. doi: 10.1093/oxfordjournals.aje.a113812. [DOI] [PubMed] [Google Scholar]
  6. Brown W. M., Doll R. Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. Br Med J. 1965 Dec 4;2(5474):1327–1332. doi: 10.1136/bmj.2.5474.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Curtis R. E., Boice J. D., Jr, Kleinerman R. A., Flannery J. T., Fraumeni J. F., Jr Summary: multiple primary cancers in Connecticut, 1935-82. Natl Cancer Inst Monogr. 1985 Dec;68:219–242. [PubMed] [Google Scholar]
  8. Curtis R. E., Hankey B. F., Myers M. H., Young J. L., Jr Risk of leukemia associated with the first course of cancer treatment: an analysis of the Surveillance, Epidemiology, and End Results Program experience. J Natl Cancer Inst. 1984 Mar;72(3):531–544. [PubMed] [Google Scholar]
  9. Doll R., Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 1981 Jun;66(6):1191–1308. [PubMed] [Google Scholar]
  10. Ewertz M., Machado S. G., Boice J. D., Jr, Jensen O. M. Endometrial cancer following treatment for breast cancer: a case-control study in Denmark. Br J Cancer. 1984 Nov;50(5):687–692. doi: 10.1038/bjc.1984.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ewertz M., Mouridsen H. T. Second cancer following cancer of the female breast in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:325–329. [PubMed] [Google Scholar]
  12. Flannery J. T., Boice J. D., Jr, Devesa S. S., Kleinerman R. A., Curtis R. E., Fraumeni J. F., Jr Cancer registration in Connecticut and the study of multiple primary cancers, 1935-82. Natl Cancer Inst Monogr. 1985 Dec;68:13–24. [PubMed] [Google Scholar]
  13. Greene M. H., Young R. C., Merrill J. M., DeVita V. T. Evidence of a treatment dose response in acute nonlymphocytic leukemias which occur after therapy of non-Hodgkin's lymphoma. Cancer Res. 1983 Apr;43(4):1891–1898. [PubMed] [Google Scholar]
  14. Gusberg S. B. Current concepts in cancer: The changing nature of endometrial cancer. N Engl J Med. 1980 Mar 27;302(13):729–731. doi: 10.1056/NEJM198003273021306. [DOI] [PubMed] [Google Scholar]
  15. Hoover R., Gray L. A., Sr, Fraumeni J. F., Jr Stilboestrol (diethylstilbestrol) and the risk of ovarian cancer. Lancet. 1977 Sep 10;2(8037):533–534. doi: 10.1016/s0140-6736(77)90667-5. [DOI] [PubMed] [Google Scholar]
  16. Ichimaru M., Ishimaru T., Belsky J. L. Incidence of leukemia in atomic bomb survivors belonging to a fixed cohort in Hiroshima and Nagasaki, 1950--71. Radiation dose, years after exposure, age at exposure, and type of leukemia. J Radiat Res. 1978 Sep;19(3):262–282. doi: 10.1269/jrr.19.262. [DOI] [PubMed] [Google Scholar]
  17. Jensen O. M., Knudsen J. B., Sørensen B. L. Second cancer following cancer of the urinary system in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:349–360. [PubMed] [Google Scholar]
  18. Jensen O. M., Storm H. H., Jensen H. S. Cancer registration in Denmark and the study of multiple primary cancers, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:245–251. [PubMed] [Google Scholar]
  19. Lynge E., Jensen O. M., Carstensen B. Second cancer following cancer of the digestive system in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:277–308. [PubMed] [Google Scholar]
  20. MOERTEL C. G., DOCKERTY M. B., BAGGENSTOSS A. H. Multiple primary malignant neoplasms. I. Introduction and presentation of data. Cancer. 1961 Mar-Apr;14:221–230. doi: 10.1002/1097-0142(196103/04)14:2<221::aid-cncr2820140202>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  21. McLaughlin J. K., Mandel J. S., Blot W. J., Schuman L. M., Mehl E. S., Fraumeni J. F., Jr A population--based case--control study of renal cell carcinoma. J Natl Cancer Inst. 1984 Feb;72(2):275–284. [PubMed] [Google Scholar]
  22. McMichael A. J., Potter J. D. Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. J Natl Cancer Inst. 1980 Dec;65(6):1201–1207. [PubMed] [Google Scholar]
  23. Monson R. R. Analysis of relative survival and proportional mortality. Comput Biomed Res. 1974 Aug;7(4):325–332. doi: 10.1016/0010-4809(74)90010-x. [DOI] [PubMed] [Google Scholar]
  24. Olsen J. H., Borch-Johnsen K., Roed-Petersen B. Rygevaner og erhvervsmaessig beskaeftigelse. Ugeskr Laeger. 1985 Aug 26;147(35):2788–2792. [PubMed] [Google Scholar]
  25. Olsen J. H. Second cancer following cancer of the respiratory system in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:309–324. [PubMed] [Google Scholar]
  26. Osterlind A., Jensen O. M. Evaluering af cancerregistreringen i Danmark 1977. En praeliminaer evaluering af cancerregisterets og landspatientregisterets registrering af cancertilfaelde. Ugeskr Laeger. 1985 Jul 29;147(31):2483–2488. [PubMed] [Google Scholar]
  27. Osterlind A., Olsen J. H., Lynge E., Ewertz M. Second cancer following cutaneous melanoma and cancers of the brain, thyroid, connective tissue, bone, and eye in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:361–388. [PubMed] [Google Scholar]
  28. Osterlind A., Rørth M., Prener A. Second cancer following cancer of the male genital system in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:341–347. [PubMed] [Google Scholar]
  29. Pedersen-Bjergaard J., Larsen S. O. Incidence of acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome up to 10 years after treatment of Hodgkin's disease. N Engl J Med. 1982 Oct 14;307(16):965–971. doi: 10.1056/NEJM198210143071601. [DOI] [PubMed] [Google Scholar]
  30. Pedersen-Bjergaard J., Philip P., Pedersen N. T., Hou-Jensen K., Svejgaard A., Jensen G., Nissen N. I. Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. II. Bone marrow cytology, cytogenetics, results of HLA typing, response to antileukemic chemotherapy, and survival in a total series of 55 patients. Cancer. 1984 Aug 1;54(3):452–462. doi: 10.1002/1097-0142(19840801)54:3<452::aid-cncr2820540313>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  31. Prentice R. L., Kato H., Yoshimoto K., Mason M. Radiation exposure and thyroid cancer incidence among Hiroshima and Nagasaki residents. Natl Cancer Inst Monogr. 1982;62:207–212. [PubMed] [Google Scholar]
  32. Prior P., Waterhouse J. A. Second primary cancers in patients with tumours of the salivary glands. Br J Cancer. 1977 Sep;36(3):362–368. doi: 10.1038/bjc.1977.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schou G., Storm H. H., Jensen O. M. Second cancer following cancers of the buccal cavity and pharynx in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:253–276. [PubMed] [Google Scholar]
  34. Smith P. G., Doll R. Late effects of x irradiation in patients treated for metropathia haemorrhagica. Br J Radiol. 1976 Mar;49(579):224–232. doi: 10.1259/0007-1285-49-579-224. [DOI] [PubMed] [Google Scholar]
  35. Storm H. H., Boice J. D., Jr Leukaemia after cervical cancer irradiation in Denmark. Int J Epidemiol. 1985 Sep;14(3):363–368. doi: 10.1093/ije/14.3.363. [DOI] [PubMed] [Google Scholar]
  36. Storm H. H., Ewertz M. Second cancer following cancer of the female genital system in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:331–340. [PubMed] [Google Scholar]
  37. Storm H. H., Jensen O. M., Ewertz M., Lynge E., Olsen J. H., Schou G., Osterlind A. Summary: multiple primary cancers in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:411–430. [PubMed] [Google Scholar]
  38. Storm H. H., Prener A. Second cancer following lymphatic and hematopoietic cancers in Denmark, 1943-80. Natl Cancer Inst Monogr. 1985 Dec;68:389–409. [PubMed] [Google Scholar]
  39. Teppo L., Pukkala E., Saxén E. Multiple cancer--an epidemiologic exercise in Finland. J Natl Cancer Inst. 1985 Aug;75(2):207–217. [PubMed] [Google Scholar]
  40. Trichopoulos D., MacMahon B., Sparros L., Merikas G. Smoking and hepatitis B-negative primary hepatocellular carcinoma. J Natl Cancer Inst. 1980 Jul;65(1):111–114. [PubMed] [Google Scholar]
  41. Wynder E. L. An epidemiological evaluation of the causes of cancer of the pancreas. Cancer Res. 1975 Aug;35(8):2228–2233. [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES