Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(3-4):673–679. doi: 10.1038/sj.bjc.6690106

Cancer risk in close relatives of women with early-onset breast cancer – a population-based incidence study

J H Olsen 1, N Seersholm 1, J D Boice Jr 2,3, S Krüger Kjær 1, J F Fraumeni Jr 3
PMCID: PMC2362425  PMID: 10027348

Abstract

Inherited susceptibility to breast cancer is associated with an early onset and bilateral disease. The extent of familial risks has not, however, been fully assessed in population-based incidence studies. The purpose of the study was to quantify the risks for cancers of the breast, ovary and other sites of close relatives of women in whom breast cancer was diagnosed at an early age. Records collected between 1943 and 1990 at the Danish Cancer Registry were searched, and 2860 women were found in whom breast cancer was diagnosed before age 40. Population registers and parish records were used to identify 14 973 parents, siblings and offspring of these women. Cancer occurrence through to 31 December 1993 was determined within the Cancer Registry's files and compared with national incidence rates. Women with early-onset breast cancer were at a nearly fourfold increased risk of developing a new cancer later in life (268 observed vs 68.9 expected). The excess risk was most evident for second cancer of the breast (181 vs 24.5) and for ovarian cancer (20 vs 3.3). For mothers and sisters, risks for cancers of the breast and ovary were significantly increased by two- to threefold. Bilateral breast cancer and breast–ovarian cancer were very strong predictors of familial risks, with one in four female relatives predicted to develop breast and/or ovarian cancer by age 75. Mothers had a slightly increased risk of colon cancer, but not endometrial cancer. The risk for breast cancer was also increased among fathers (standardized incidence ratio 2.5; 95% CI 0.5–7.4) and especially brothers (29; 7.7–74), although based on small numbers. The risk for prostatic cancer was unremarkable. In this large population-based survey, the first-degree relatives of women who developed breast cancer before age 40 were prone to ovarian cancer as well as male and female breast cancer, but not other tumours that may share susceptibility genes with breast cancer. © 1999 Cancer Research Campaign

Keywords: early-onset breast cancer, familial cancer, heriditary cancer syndromes, cancer susceptibility genes

Full Text

The Full Text of this article is available as a PDF (96.8 KB).

Selected References

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

  1. Amos C. I., Struewing J. P. Genetic epidemiology of epithelial ovarian cancer. Cancer. 1993 Jan 15;71(2 Suppl):566–572. doi: 10.1002/cncr.2820710212. [DOI] [PubMed] [Google Scholar]
  2. Anderson D. E., Badzioch M. D. Familial breast cancer risks. Effects of prostate and other cancers. Cancer. 1993 Jul 1;72(1):114–119. doi: 10.1002/1097-0142(19930701)72:1<114::aid-cncr2820720122>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  3. Anderson K. E., Easton D. F., Matthews F. E., Peto J. Cancer mortality in the first degree relatives of young breast cancer patients. Br J Cancer. 1992 Sep;66(3):599–602. doi: 10.1038/bjc.1992.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bebb G., Glickman B., Gelmon K., Gatti R. "AT risk" for breast cancer. Lancet. 1997 Jun 21;349(9068):1784–1785. doi: 10.1016/S0140-6736(05)61687-X. [DOI] [PubMed] [Google Scholar]
  5. Boice J. D., Jr, Harvey E. B., Blettner M., Stovall M., Flannery J. T. Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med. 1992 Mar 19;326(12):781–785. doi: 10.1056/NEJM199203193261201. [DOI] [PubMed] [Google Scholar]
  6. Claus E. B., Risch N. J., Thompson W. D. Age at onset as an indicator of familial risk of breast cancer. Am J Epidemiol. 1990 Jun;131(6):961–972. doi: 10.1093/oxfordjournals.aje.a115616. [DOI] [PubMed] [Google Scholar]
  7. Claus E. B., Risch N., Thompson W. D. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet. 1991 Feb;48(2):232–242. [PMC free article] [PubMed] [Google Scholar]
  8. Eby N., Chang-Claude J., Bishop D. T. Familial risk and genetic susceptibility for breast cancer. Cancer Causes Control. 1994 Sep;5(5):458–470. doi: 10.1007/BF01694760. [DOI] [PubMed] [Google Scholar]
  9. FitzGerald M. G., Bean J. M., Hegde S. R., Unsal H., MacDonald D. J., Harkin D. P., Finkelstein D. M., Isselbacher K. J., Haber D. A. Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet. 1997 Mar;15(3):307–310. doi: 10.1038/ng0397-307. [DOI] [PubMed] [Google Scholar]
  10. FitzGerald M. G., MacDonald D. J., Krainer M., Hoover I., O'Neil E., Unsal H., Silva-Arrieto S., Finkelstein D. M., Beer-Romero P., Englert C. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med. 1996 Jan 18;334(3):143–149. doi: 10.1056/NEJM199601183340302. [DOI] [PubMed] [Google Scholar]
  11. Ford D., Easton D. F., Peto J. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet. 1995 Dec;57(6):1457–1462. [PMC free article] [PubMed] [Google Scholar]
  12. Franceschi S., Dal Maso L., Lo Re A., Serraino D., La Vecchia C. Trends of Kaposi's sarcoma at AIDS diagnosis in Europe and the United States, 1987-94. Br J Cancer. 1997;76(1):114–117. doi: 10.1038/bjc.1997.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garber J. E., Goldstein A. M., Kantor A. F., Dreyfus M. G., Fraumeni J. F., Jr, Li F. P. Follow-up study of twenty-four families with Li-Fraumeni syndrome. Cancer Res. 1991 Nov 15;51(22):6094–6097. [PubMed] [Google Scholar]
  14. Goldgar D. E., Easton D. F., Cannon-Albright L. A., Skolnick M. H. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994 Nov 2;86(21):1600–1608. doi: 10.1093/jnci/86.21.1600. [DOI] [PubMed] [Google Scholar]
  15. Gudmundsson J., Johannesdottir G., Arason A., Bergthorsson J. T., Ingvarsson S., Egilsson V., Barkardottir R. B. Frequent occurrence of BRCA2 linkage in Icelandic breast cancer families and segregation of a common BRCA2 haplotype. Am J Hum Genet. 1996 Apr;58(4):749–756. [PMC free article] [PubMed] [Google Scholar]
  16. Inskip P. D., Stovall M., Flannery J. T. Lung cancer risk and radiation dose among women treated for breast cancer. J Natl Cancer Inst. 1994 Jul 6;86(13):983–988. doi: 10.1093/jnci/86.13.983. [DOI] [PubMed] [Google Scholar]
  17. Krainer M., Silva-Arrieta S., FitzGerald M. G., Shimada A., Ishioka C., Kanamaru R., MacDonald D. J., Unsal H., Finkelstein D. M., Bowcock A. Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. N Engl J Med. 1997 May 15;336(20):1416–1421. doi: 10.1056/NEJM199705153362003. [DOI] [PubMed] [Google Scholar]
  18. Langston A. A., Malone K. E., Thompson J. D., Daling J. R., Ostrander E. A. BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med. 1996 Jan 18;334(3):137–142. doi: 10.1056/NEJM199601183340301. [DOI] [PubMed] [Google Scholar]
  19. Li F. P., Fraumeni J. F., Jr, Mulvihill J. J., Blattner W. A., Dreyfus M. G., Tucker M. A., Miller R. W. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988 Sep 15;48(18):5358–5362. [PubMed] [Google Scholar]
  20. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S. I., Puc J., Miliaresis C., Rodgers L., McCombie R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943–1947. doi: 10.1126/science.275.5308.1943. [DOI] [PubMed] [Google Scholar]
  21. Malone K. E., Daling J. R., Thompson J. D., O'Brien C. A., Francisco L. V., Ostrander E. A. BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history. JAMA. 1998 Mar 25;279(12):922–929. doi: 10.1001/jama.279.12.922. [DOI] [PubMed] [Google Scholar]
  22. Negri E., Braga C., La Vecchia C., Franceschi S., Parazzini F. Family history of cancer and risk of breast cancer. Int J Cancer. 1997 Sep 4;72(5):735–738. doi: 10.1002/(sici)1097-0215(19970904)72:5<735::aid-ijc5>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  23. Olsen J. H., Boice J. D., Jr, Seersholm N., Bautz A., Fraumeni J. F., Jr Cancer in the parents of children with cancer. N Engl J Med. 1995 Dec 14;333(24):1594–1599. doi: 10.1056/NEJM199512143332403. [DOI] [PubMed] [Google Scholar]
  24. Peto J., Easton D. F., Matthews F. E., Ford D., Swerdlow A. J. Cancer mortality in relatives of women with breast cancer: the OPCS Study. Office of Population Censuses and Surveys. Int J Cancer. 1996 Jan 26;65(3):275–283. doi: 10.1002/(SICI)1097-0215(19960126)65:3<275::AID-IJC1>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  25. Pharoah P. D., Day N. E., Duffy S., Easton D. F., Ponder B. A. Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer. 1997 May 29;71(5):800–809. doi: 10.1002/(sici)1097-0215(19970529)71:5<800::aid-ijc18>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  26. Rebbeck T. R., Couch F. J., Kant J., Calzone K., DeShano M., Peng Y., Chen K., Garber J. E., Weber B. L. Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. Am J Hum Genet. 1996 Sep;59(3):547–553. [PMC free article] [PubMed] [Google Scholar]
  27. Schildkraut J. M., Risch N., Thompson W. D. Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship. Am J Hum Genet. 1989 Oct;45(4):521–529. [PMC free article] [PubMed] [Google Scholar]
  28. Sellers T. A., Potter J. D., Rich S. S., Drinkard C. R., Bostick R. M., Kushi L. H., Zheng W., Folsom A. R. Familial clustering of breast and prostate cancers and risk of postmenopausal breast cancer. J Natl Cancer Inst. 1994 Dec 21;86(24):1860–1865. doi: 10.1093/jnci/86.24.1860. [DOI] [PubMed] [Google Scholar]
  29. Slattery M. L., Kerber R. A. A comprehensive evaluation of family history and breast cancer risk. The Utah Population Database. JAMA. 1993 Oct 6;270(13):1563–1568. [PubMed] [Google Scholar]
  30. Storm H. H., Andersson M., Boice J. D., Jr, Blettner M., Stovall M., Mouridsen H. T., Dombernowsky P., Rose C., Jacobsen A., Pedersen M. Adjuvant radiotherapy and risk of contralateral breast cancer. J Natl Cancer Inst. 1992 Aug 19;84(16):1245–1250. doi: 10.1093/jnci/84.16.1245. [DOI] [PubMed] [Google Scholar]
  31. Struewing J. P., Hartge P., Wacholder S., Baker S. M., Berlin M., McAdams M., Timmerman M. M., Brody L. C., Tucker M. A. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997 May 15;336(20):1401–1408. doi: 10.1056/NEJM199705153362001. [DOI] [PubMed] [Google Scholar]
  32. Struewing J. P., Tarone R. E., Brody L. C., Li F. P., Boice J. D., Jr BRCA1 mutations in young women with breast cancer. Lancet. 1996 May 25;347(9013):1493–1493. doi: 10.1016/s0140-6736(96)91732-8. [DOI] [PubMed] [Google Scholar]
  33. Teare M. D., Wallace S. A., Harris M., Howell A., Birch J. M. Cancer experience in the relatives of an unselected series of breast cancer patients. Br J Cancer. 1994 Jul;70(1):102–111. doi: 10.1038/bjc.1994.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tulinius H., Olafsdottir G. H., Sigvaldason H., Tryggvadottir L., Bjarnadottir K. Neoplastic diseases in families of breast cancer patients. J Med Genet. 1994 Aug;31(8):618–621. doi: 10.1136/jmg.31.8.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tulinius H., Sigvaldason H., Olafsdóttir G., Tryggvadóttir L. Epidemiology of breast cancer in families in Iceland. J Med Genet. 1992 Mar;29(3):158–164. doi: 10.1136/jmg.29.3.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Whittemore A. S., Gong G., Itnyre J. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer. Am J Hum Genet. 1997 Mar;60(3):496–504. [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES