Affiliation of authors: K. Hemminki, Chuanhui Dong, Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden.
Correspondence to: Kari Hemminki, M.D., Ph.D., Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden.
Bonnet and co-workers (1) presented evidence on the presence of Epstein-Barr virus (EBV) sequences in breast cancer cells. We wanted to examine whether epidemiologic evidence would support the role of EBV infection in breast cancer. The tumorigenicity of EBV appears best established for Hodgkin's disease in Europe and North America; some 40% of Hodgkin's disease cases are attributed to EBV infection (2), and most show viral genomes in serum (3). We reason that, if breast cancer were related to EBV, we should find an epidemiologic association between breast cancer and Hodgkin's disease. Saliva is the main route of EBV infection (4), and family members of women with breast cancer should show an excess of Hodgkin's disease if EBV were the shared etiologic agent. To test these hypotheses, we used the nationwide Swedish Family-Cancer Database on 9.6 million people organized in families and containing cancer data from the Swedish Cancer Registry from years 1958 through 1996 (5). Standardized incidence ratios (SIRs) were calculated based on age-standardized national rates available from the database; 95% confidence intervals (95% CI) were calculated assuming a Poisson distribution. We first analyzed Hodgkin's disease incidence as a second cancer in women diagnosed with breast cancer. There were 21 cases giving an SIR of 1.05 (95% CI = 0.65-1.55). Analyzing breast cancer incidence after Hodgkin's disease showed an SIR of 2.32 (n = 45; 95% CI = 1.69-3.04), but the excess was only observed greater than or equal to 5 years after Hodgkin's disease, a well-known effect of radiotherapy (6); only two cases occurred 0-4 years after Hodgkin's disease diagnosis, while 7.44 cases were expected.
As a second hypothesis, we examined breast cancers and Hodgkin's disease incidence
in daughters of mothers who had either disease, but there was no increase in any SIR (Table 1). We found 88 couples in whom the wife presented with breast cancer and
the husband with Hodgkin's disease; the SIR for the wife with breast cancer was 0.94, and
the SIR for the husband with Hodgkin's disease was 1.01. In one couple, both spouses
presented with Hodgkin's disease compared with 1.6 couples expected. We thus failed to
verify the hypotheses linking breast cancer and EBV, using Hodgkin's disease as a
surrogate marker for EBV infection.
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REFERENCES
1
Bonnet M, Guinebretiere JM, Kremmer E, Grunewald V,
Benhamou E, Contesso G, et al. Detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst 1999;91:1376-81.
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3 Gallagher A, Armstrong AA, MacKenzie J, Shiled L, Khan G, Lake A, et al. Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin's disease. Int J Cancer (Pred Oncol) 1999;84:442-8.[Medline]
4
Magrath I, Bhatia K. Breast cancer: a new Epstein-Barr
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5 Hemminki K, Dong C, Vaittinen P. Familial risks in cervix cancer: is there a hereditary component? Int J Cancer 1999;82:775-81.[Medline]
6 Aisenberg AC, Finkelstein DM, Doppke KP, Koerner FC, Boivin JF, Willett CG. High risk of breast carcinoma after irradiation of young women with Hodgkin's disease. Cancer 1997;79:1203-10.[Medline]
7 Hemminki K, Dong C. Primary cancers following squamous cell carcinoma of the skin suggest involvement of Epstein-Barr virus [letter].Epidemiology . In press 2000.
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