Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jan 18;82(2):446–451. doi: 10.1054/bjoc.1999.0941

Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus

T H M Stewart 1, R D Sage 2, A F R Stewart 3, D W Cameron 1
PMCID: PMC2363264  PMID: 10646903

Abstract

Incidence of human breast cancer (HBC) varies geographically, but to date no environmental factor has explained this variation. Previously, we reported a 44% reduction in the incidence of breast cancer in women fully immunosuppressed following organ transplantation (Stewart et al (1995) Lancet346: 796–798). In mice infected with the mouse mammary tumour virus (MMTV), immunosuppression also reduces the incidence of mammary tumours. DNA with 95% identity to MMTV is detected in 40% of human breast tumours (Wang et al (1995) Cancer Res55: 5173–5179). These findings led us to ask whether the incidence of HBC could be correlated with the natural ranges of different species of wild mice. We found that the highest incidence of HBC worldwide occurs in lands where Mus domesticus is thse resident native or introduced species of house mouse. Given the similar responses of humans and mice to immunosuppression, the near identity between human and mouse MTV DNA sequences, and the close association between HBC incidence and mouse ranges, we propose that humans acquire MMTV from mice. This zoonotic theory for a mouse-viral cause of HBC allows testable predictions and has potential importance in prevention. © 2000 Cancer Research Campaign

Keywords: human breast cancer, mouse mammary tumour virus, zoonosis, geographic variation, incidence, Mus domesticus, MMTV

Full Text

The Full Text of this article is available as a PDF (117.4 KB).

Selected References

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

  1. Ayotte P., Dewailly E., Ryan J. J., Bruneau S., Lebel G. PCBs and dioxin-like compounds in plasma of adult Inuit living in Nunavik (Arctic Quebec). Chemosphere. 1997 Mar-Apr;34(5-7):1459–1468. doi: 10.1016/s0045-6535(97)00442-6. [DOI] [PubMed] [Google Scholar]
  2. Blank R. D., Campbell G. R., D'Eustachio P. Possible derivation of the laboratory mouse genome from multiple wild Mus species. Genetics. 1986 Dec;114(4):1257–1269. doi: 10.1093/genetics/114.4.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brandt-Carlson C., Butel J. S., Wheeler D. Phylogenetic and structural analyses of MMTV LTR ORF sequences of exogenous and endogenous origins. Virology. 1993 Mar;193(1):171–185. doi: 10.1006/viro.1993.1113. [DOI] [PubMed] [Google Scholar]
  4. Bui T. D., Rankin J., Smith K., Huguet E. L., Ruben S., Strachan T., Harris A. L., Lindsay S. A novel human Wnt gene, WNT10B, maps to 12q13 and is expressed in human breast carcinomas. Oncogene. 1997 Mar 13;14(10):1249–1253. doi: 10.1038/sj.onc.1200936. [DOI] [PubMed] [Google Scholar]
  5. Callahan R., Drohan W., Gallahan D., D'Hoostelaere L., Potter M. Novel class of mouse mammary tumor virus-related DNA sequences found in all species of Mus, including mice lacking the virus proviral genome. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4113–4117. doi: 10.1073/pnas.79.13.4113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Callahan R., Gallahan D., D'Hoostelaere L. A., Potter M. Endogenous MMTV proviral genomes in feral Mus musculus domesticus. Curr Top Microbiol Immunol. 1986;127:362–370. doi: 10.1007/978-3-642-71304-0_44. [DOI] [PubMed] [Google Scholar]
  7. Callahan R. MMTV-induced mutations in mouse mammary tumors: their potential relevance to human breast cancer. Breast Cancer Res Treat. 1996;39(1):33–44. doi: 10.1007/BF01806076. [DOI] [PubMed] [Google Scholar]
  8. Chie W. C., Chen C. F., Chen C. J., Chang C. L., Liaw Y. P., Lin R. S. Geographic variation of breast cancer in Taiwan: international and migrant comparison. Anticancer Res. 1995 Nov-Dec;15(6B):2745–2749. [PubMed] [Google Scholar]
  9. Cohen J. C., Varmus H. E. Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding. Nature. 1979 Mar 29;278(5703):418–423. doi: 10.1038/278418a0. [DOI] [PubMed] [Google Scholar]
  10. Day N. K., Witkin S. S., Sarkar N. H., Kinne D., Jussawalla D. J., Levin A., Hsia C. C., Geller N., Good R. A. Antibodies reactive with murine mammary tumor virus in sera of patients with breast cancer: geographic and family studies. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2483–2487. doi: 10.1073/pnas.78.4.2483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dion A. S., Girardi A. J., Williams C. C., Pomenti A. A. Serologic responses to murine mammary tumor virus (MuMTV) in MuMTV-exposed laboratory personnel. J Natl Cancer Inst. 1986 Apr;76(4):611–619. doi: 10.1093/jnci/76.4.611. [DOI] [PubMed] [Google Scholar]
  12. Dmochowski L., Seman G., Gallager H. S. Viruses as possible etiologic factors in human breast cancer. Cancer. 1969 Dec;24(6):1241–1249. doi: 10.1002/1097-0142(196912)24:6<1241::aid-cncr2820240630>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  13. Doll R. The geographical distribution of cancer. Br J Cancer. 1969 Mar;23(1):1–8. doi: 10.1038/bjc.1969.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Doolittle R. F., Feng D. F., Johnson M. S., McClure M. A. Origins and evolutionary relationships of retroviruses. Q Rev Biol. 1989 Mar;64(1):1–30. doi: 10.1086/416128. [DOI] [PubMed] [Google Scholar]
  15. Golovkina T. V., Jaffe A. B., Ross S. R. Coexpression of exogenous and endogenous mouse mammary tumor virus RNA in vivo results in viral recombination and broadens the virus host range. J Virol. 1994 Aug;68(8):5019–5026. doi: 10.1128/jvi.68.8.5019-5026.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Holder W. D., Jr, Peer G. W., Bolognesi D. P., Wells S. A., Jr Antibody reacting with mouse mammary tumor virus in serum of breast carcinoma patients. Surg Forum. 1976;27(62):102–104. [PubMed] [Google Scholar]
  17. Holmes M. D., Hunter D. J., Colditz G. A., Stampfer M. J., Hankinson S. E., Speizer F. E., Rosner B., Willett W. C. Association of dietary intake of fat and fatty acids with risk of breast cancer. JAMA. 1999 Mar 10;281(10):914–920. doi: 10.1001/jama.281.10.914. [DOI] [PubMed] [Google Scholar]
  18. Howard D. K., Schlom J. Isolation of a series of novel variants of murine mammary tumor viruses with broadened host ranges. Int J Cancer. 1980 May 15;25(5):647–654. doi: 10.1002/ijc.2910250515. [DOI] [PubMed] [Google Scholar]
  19. Huguet E. L., McMahon J. A., McMahon A. P., Bicknell R., Harris A. L. Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue. Cancer Res. 1994 May 15;54(10):2615–2621. [PubMed] [Google Scholar]
  20. Hunter D. J., Hankinson S. E., Laden F., Colditz G. A., Manson J. E., Willett W. C., Speizer F. E., Wolff M. S. Plasma organochlorine levels and the risk of breast cancer. N Engl J Med. 1997 Oct 30;337(18):1253–1258. doi: 10.1056/NEJM199710303371801. [DOI] [PubMed] [Google Scholar]
  21. Hunter D. J., Spiegelman D., Adami H. O., Beeson L., van den Brandt P. A., Folsom A. R., Fraser G. E., Goldbohm R. A., Graham S., Howe G. R. Cohort studies of fat intake and the risk of breast cancer--a pooled analysis. N Engl J Med. 1996 Feb 8;334(6):356–361. doi: 10.1056/NEJM199602083340603. [DOI] [PubMed] [Google Scholar]
  22. Imai S. Mouse mammary tumor virus and mammary tumorigenesis in wild mice. Pathol Int. 1996 Dec;46(12):919–932. doi: 10.1111/j.1440-1827.1996.tb03570.x. [DOI] [PubMed] [Google Scholar]
  23. Imai S., Okumoto M., Iwai M., Haga S., Mori N., Miyashita N., Moriwaki K., Hilgers J., Sarkar N. H. Distribution of mouse mammary tumor virus in Asian wild mice. J Virol. 1994 May;68(5):3437–3442. doi: 10.1128/jvi.68.5.3437-3442.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Iscovich J., Howe G. R. Cancer incidence patterns (1972-91) among migrants from the Soviet Union to Israel. Cancer Causes Control. 1998 Jan;9(1):29–36. doi: 10.1023/a:1008893102428. [DOI] [PubMed] [Google Scholar]
  25. Jouvin-Marche E., Cazenave P. A., Voegtle D., Marche P. N. V beta 17 T-cell deletion by endogenous mammary tumor virus in wild-type-derived mouse strain. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3232–3235. doi: 10.1073/pnas.89.8.3232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kozak C., Peters G., Pauley R., Morris V., Michalides R., Dudley J., Green M., Davisson M., Prakash O., Vaidya A. A standardized nomenclature for endogenous mouse mammary tumor viruses. J Virol. 1987 May;61(5):1651–1654. doi: 10.1128/jvi.61.5.1651-1654.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Labrecque N., McGrath H., Subramanyam M., Huber B. T., Sékaly R. P. Human T cells respond to mouse mammary tumor virus-encoded superantigen: V beta restriction and conserved evolutionary features. J Exp Med. 1993 Jun 1;177(6):1735–1743. doi: 10.1084/jem.177.6.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lasfargues E. Y., Coutinho W. G., Dion A. S. A human breast tumor cell line (BT-474) that supports mouse mammary tumor virus replication. In Vitro. 1979 Sep;15(9):723–729. doi: 10.1007/BF02618252. [DOI] [PubMed] [Google Scholar]
  29. Lasfargues E. Y., Lasfargues J. C., Dion A. S., Greene A. E., Moore D. H. Experimental infection of a cat kidney cell line with the mouse mammary tumor virus. Cancer Res. 1976 Jan;36(1):67–72. [PubMed] [Google Scholar]
  30. Lasfargues E. Y., Vaidya A. B., Lasfargues J. C., Moore D. H. In vitro susceptibility of mink lung cells to the mouse mammary tumor virus. J Natl Cancer Inst. 1976 Aug;57(2):447–449. doi: 10.1093/jnci/57.2.447. [DOI] [PubMed] [Google Scholar]
  31. Lopez D. M., Parks W. P., Silverman M. A., Distasio J. A. Lymphoproliferative responses to mouse mammary tumor virus in lymphocyte subsets of breast cancer patients. J Natl Cancer Inst. 1981 Aug;67(2):353–358. [PubMed] [Google Scholar]
  32. Lushnikova A. A., Kriukova I. N., Malivanova T. F., Makhov P. B., Polevaia E. B. Korreliatsiia mezhdu ékspressiei antigena, immunologicheski rodstvennogo gp52, i transkriptsiei gomologichnykh ENV MMTV posledovatel'nostei DNK v limfotsitakh perifericheskoi krovi bol'nykh rakom molochnoi zhelezy. Mol Gen Mikrobiol Virusol. 1998;(3):33–36. [PubMed] [Google Scholar]
  33. Miller A. B., Gaudette L. A. Breast cancer in Circumpolar Inuit 1969-1988. Acta Oncol. 1996;35(5):577–580. doi: 10.3109/02841869609096989. [DOI] [PubMed] [Google Scholar]
  34. Mills J. N., Childs J. E. Ecologic studies of rodent reservoirs: their relevance for human health. Emerg Infect Dis. 1998 Oct-Dec;4(4):529–537. doi: 10.3201/eid0404.980403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nishio M, Xu L, Sasaki M, Haga S, Okumoto M, Mori N, Sarkar NH, Acha-Orbea H, Enami J, Imai S. Complete Nucleotide Sequence of Mouse Mammary Tumor Virus from JYG Chinese Wild Mice: Absence of Bacterial Insertion Sequences in the Cloned Viral gag Gene. Breast Cancer. 1994 Dec 30;1(2):89–94. doi: 10.1007/BF02967037. [DOI] [PubMed] [Google Scholar]
  36. Nusse R. Insertional mutagenesis in mouse mammary tumorigenesis. Curr Top Microbiol Immunol. 1991;171:43–65. doi: 10.1007/978-3-642-76524-7_3. [DOI] [PubMed] [Google Scholar]
  37. POGOSSIANTZ H. Some data on the experimental studies of the nature of mammary cancer in mice carried out in the Soviet Union. Acta Unio Int Contra Cancrum. 1956;12(5-6):690-8; discussion, 698-700. [PubMed] [Google Scholar]
  38. Poon M. C., Tomana M., Niedermeier W. Serum antibodies against mouse mammary tumor-virus-associated antigen detected nine months before appearance of a breast carcinoma. Ann Intern Med. 1983 Jun;98(6):937–938. doi: 10.7326/0003-4819-98-6-937. [DOI] [PubMed] [Google Scholar]
  39. Ringold G. M., Cardiff R. D., Varmus H. E., Yamamoto K. R. Infection of cultured rat hepatoma cells by mouse mammary tumor virus. Cell. 1977 Jan;10(1):11–18. doi: 10.1016/0092-8674(77)90134-9. [DOI] [PubMed] [Google Scholar]
  40. Rongey R. W., Hlavackova A., Lara S., Estes J., Gardner M. B. Types B and C RNA virus in breast tissue and milk of wild mice. J Natl Cancer Inst. 1973 Jun;50(6):1581–1589. doi: 10.1093/jnci/50.6.1581. [DOI] [PubMed] [Google Scholar]
  41. Stewart T. H., Heppner G. H. Immunological enhancement of breast cancer. Parasitology. 1997;115 (Suppl):S141–S153. doi: 10.1017/s0031182097001832. [DOI] [PubMed] [Google Scholar]
  42. Stewart T., Tsai S. C., Grayson H., Henderson R., Opelz G. Incidence of de-novo breast cancer in women chronically immunosuppressed after organ transplantation. Lancet. 1995 Sep 23;346(8978):796–798. doi: 10.1016/s0140-6736(95)91618-0. [DOI] [PubMed] [Google Scholar]
  43. Szabo C. I., King M. C. Population genetics of BRCA1 and BRCA2. Am J Hum Genet. 1997 May;60(5):1013–1020. [PMC free article] [PubMed] [Google Scholar]
  44. Tajima K., Cartier L. Epidemiological features of HTLV-I and adult T cell leukemia. Intervirology. 1995;38(3-4):238–246. doi: 10.1159/000150438. [DOI] [PubMed] [Google Scholar]
  45. Titus-Ernstoff L., Egan K. M., Newcomb P. A., Baron J. A., Stampfer M., Greenberg E. R., Cole B. F., Ding J., Willett W., Trichopoulos D. Exposure to breast milk in infancy and adult breast cancer risk. J Natl Cancer Inst. 1998 Jun 17;90(12):921–924. doi: 10.1093/jnci/90.12.921. [DOI] [PubMed] [Google Scholar]
  46. Traina-Dorge V., Cohen J. C. Molecular genetics of mouse mammary tumor virus. Curr Top Microbiol Immunol. 1983;106:35–56. doi: 10.1007/978-3-642-69357-1_2. [DOI] [PubMed] [Google Scholar]
  47. Wang Y., Holland J. F., Bleiweiss I. J., Melana S., Liu X., Pelisson I., Cantarella A., Stellrecht K., Mani S., Pogo B. G. Detection of mammary tumor virus env gene-like sequences in human breast cancer. Cancer Res. 1995 Nov 15;55(22):5173–5179. [PubMed] [Google Scholar]
  48. Wei W. Z., Gill R. F., Wang H. Mouse mammary tumor virus associated antigens and superantigens--immuno-molecular correlates of neoplastic progression. Semin Cancer Biol. 1993 Jun;4(3):205–213. [PubMed] [Google Scholar]
  49. Winter H., Cheng K. K., Cummins C., Maric R., Silcocks P., Varghese C. Cancer incidence in the south Asian population of England (1990-92). Br J Cancer. 1999 Feb;79(3-4):645–654. doi: 10.1038/sj.bjc.6690102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wiseman C. L., Bowen J. M., Davis J. W., Hersh E. M., Brown B. W., Blumenschein G. R. Human lymphocyte blastogenesis responses to mouse mammary tumor virus. J Natl Cancer Inst. 1980 Mar;64(3):425–430. [PubMed] [Google Scholar]
  51. Ziegler R. G., Hoover R. N., Pike M. C., Hildesheim A., Nomura A. M., West D. W., Wu-Williams A. H., Kolonel L. N., Horn-Ross P. L., Rosenthal J. F. Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst. 1993 Nov 17;85(22):1819–1827. doi: 10.1093/jnci/85.22.1819. [DOI] [PubMed] [Google Scholar]
  52. Zotter S. Widespread occurrence in mammals of antibodies reactive to intracytoplasmic A particles of the mouse mammary tumor virus. Arch Geschwulstforsch. 1983;53(4):315–319. [PubMed] [Google Scholar]

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

RESOURCES