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Letter to the Editor

Reproductive factors are crucial in the aetiology of breast cancer

Sir, Stewart et al (2000) propose that humans acquire mouse mam tumour virus (MMTV) from mice. They advocate a viral aetiolo for the high incidence of human breast cancer (HBC) and a against other possible aetiological factors. However, their st tical analysis is simplistic and ignores social, cultural and de graphic variables that are known to affect the risk of breast ca (Gilliland, 1997). Two countries, Algeria (low incidence rate a in the lands of M. domesticus) and Finland (high incidence rat and in the lands of M. musculus) contradict the viral theory for HBC. While the authors do not explain the findings Algeria they suggest cross-breeding between M. domesticusand M. musculusin Finland. We believe that socio-cultural and dem graphic variables contribute significantly to the low inciden We also note that in Finland, HBC was most common in h social classes throughout the period 1971–1995 (Pukkala Weiderpass, 1999).

It is well established that a woman’s reproductive history in ences her risk of HBC (Kelsey et al, 1993). Among reproduc and hormonal factors, the most important known determin of breast cancer are late age at first birth and nulliparity, e menopause and use of hormone-replacement therapy. In Ita land of M. domesticus), the combination of risks associated with high level of education, old age at first birth and nulliparity a older age at menopause accounted for 51% of breast c cases (Tavani et al, 1997). The lowest HBC incidence rate in world (South Korea, a land inhabited by other mice) was attrib to late age at menarche, early age at natural menopause, age at first full-term pregnancy and larger number of full-te pregnancies (Suh et al, 1996).

In Taiwan (a land inhabited by other mice) Chinese wom were found to have lower incidence rates than white women o same area (Chie et al, 1995). A substantial increase in HBC ri women who migrated from Asia to the USA was demonstra with the risk doubling during the first decade after migrati Increased use of contraceptive soon after migration to the could possibly explain this rapid rise in risk (Ursin et al, 1995) the USA (a high-incidence country) the incidence rates diffe among 25 counties in the San Francisco Bay area and corre with the distribution of known risk factors (Robbins et al, 19 Prehn and West, 1998). Moreover, Hispanic women living in USA have been shown to have the lowest incidence across geographic regions of the USA (Jones et al, 1997).

The incidence of breast cancer is increasing more rapidl societies that enjoyed a low incidence of the disease, such as

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African countries. This is partly a result of the changing dem graphic profile, acquisition of ‘Western’ lifestyle, and th changing socioeconomic profile of the country (Adebamowo a Adekunle, 1999).

The reported relation between M. domesticusand HBC suffers from ecological bias because it does not take into consideratio density of mice population and its correlation with HBC inc dence-rate. It will be interesting to see whether this relation hold after adjusting for both human reproductive factors and m population density.

SA Khuder, AB Mutgi Medical College of Ohio, USA

REFERENCES

Adebamowo CA and Adekule OO (1999) Case-controlled study of the epidemiological risk factors for breast cancer in Nigeria. Br J Surg86: 665–668

Chie WC, Chen CF, Chen CJ, Chang CL, Liaw YP and Lin RS (1995) Geograph variation of breast cancer in Taiwan: international and migrant comparison. Anticancer Res15: 2745–2749

Gilliland FD (1997) Ethnic differences in cancer incidence: a marker for inherited susceptibility? Environ Health Perspect105(suppl 4): 497–900

Jones LA, Gonzalez R, Pillow PC, Gomez-Garza SA, Foreman CJ, Chilton JA, Linares A, Yick J, Badrei M and Hajek RA (1997) Dietary fiber, Hispanics, and breast cancer risk? Ann NY Acad Sci837: 254–236

Kelsey JL, Gammon MD and John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev15: 36–47

Prehn AW and West DW (1998) Evaluating local differences in breast cancer incidence rates: a census-based methodology (United States). Cancer Causes Control 9: 511–517

Pukkala E and Weiderpass E (1999) Time trends in socio-economic differences incidence rates of cancers of the breast and female genital organs (Finland 1971–1995). Int J Cancer31: 56–61

Robbins AS, Brescianini S and Kelsey JL (1997) Regional differences in known factors and higher incidence of breast cancer in San Francisco. J Natl Cancer Inst 89: 960–965

Stewart THM, Sage RD, Stewart AFR and Cameron DW (2000) Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus. Br J Cancer82: 446–451

Suh JS, Yoo KY, Kwon OJ, Yun IJ, Han SH, Noh DY and Choe KJ (1996) Menstrual and reproductive factors related to the risk of breast cancer in Ko Ovarian hormone effect on breast cancer. J Korean Med Sci11: 501–508

Tavani A, Braga C, La Vecchia C, Negri E, Russo A and Franceschi S (1997) Attributable risks for breast cancer in Italy: education, family history and reproductive and hormonal factors. Int J Cancer70: 159–163

Ursin G, Wu AH, Hoover RN, West DW, Nomura AM, Kolonel LN and Ziegler RG (1999) Breast cancer and oral contraceptive use in Asian-American women Am J Epidemiol150: 561–567

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134 Letter to the Editor

Reproductive factors are crucial in the aetiology of breast cancer Ð a reply

doi: 10.1054/ bjoc.2000.1312, available online at http://www.idealibrary.com on

Sir, The letter by Professor Khuder raises several points of pote importance. Our statistical analysis correlating Mus species and human breast cancer (HBC) incidence is described as simpl ignoring social, cultural and demographic variables. Thus, it m suffer from ecological bias, due to the effect of hormo promoters on the development of HBC. The greatest influe would likely be associated with fecundity, which is best reflec in the world statistics on ‘total fertility rate’ (TFR) (US Bureau the Census, Report WP/98, World Population Profile (1998) Government Printing Office: Washington DC, 1999).

TFR was evaluated as a potential confounder of the associ of M. domesticusgeography with human breast cancer inciden For our sample of 39 countries (less two regions, Hawaii ‘circumpolar Inuit’ for want of data), we analysed the repor 1990 (or 1998, where lacking) TFR for correlation with the wo age-standardized incidence rate (WASIR) for female breast ca (as in Stewart et al, 2000). The expected negative correlatio WASIR with TFR [R = –0.327, P = 0.048] was found. However across Europe there was no difference in TFR between lands M. domesticusand lands of other mice (mean TFR 1.656 ± SD 0.368, vs 1.657 ± 0.346, P = 0.993).

Internationally, excluding Europe, there was a higher repo TFR in M. domesticuslands (TFR 2.875 ± 0.822 vs 2.371 ± 0.971, P = 0.244). Overall, the crude difference in mean WASIR due M. domesticuslands is +15.6, accounting for 38.3% of th observed variation in this sample. The TFR-adjusted differenc mean WASIR is + 17.4, accounting for 48.4% of variation, b highly statistically significant (P < 0.001). Thus, in addressin Professor Khuder’s concern about reproductive factors adjusting for TFR, the association of WASIR with lands of M. domesticuswas strengthened.

The report by McCredie et al (1999) on the incidence of HBC Maori and non Maori women emphasizes that all parame suggesting a lower incidence of HBC were seen in Maori wom in a highly significant fashion, lower educational level, low socio-economic status, lower age at first full term pregnancy, parity and longer duration of breast-feeding. Despite this, the dence of HBC in Maori women before the age of 54 is twice of non-Maori women in New Zealand. Could this reflect a grea exposure of the Maori to Mus domesticuswhich occurs in both urban areas and native forests in New Zealand (King, 1982)?

In the paper by Chie et al (1995), no data on the incidenc HBC in white women is given in the text. White women form minuscule proportion of the female population of Taiwan. The of oral contraceptives in Asian women migrating to the US adjusted for age, ethnicity, study area, years since migra

British Journal of Cancer (2000) 83(1), 133–134

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family history of HBC and age at first full-term birth was not as ciated with increased risk of breast cancer (Ursin et al, 1999). low incidence of HBC in Spanish women and Hispanic wom living in the US is a fact. Genetic susceptibility to MMTV was n addressed in our paper, although it has been well studied in (Ross et al 1997; Golovkina, 2000).

In summary, adjustment of our analysis for a possible ecol bias related to fecundity and hormonal influence on breast ca increases the statistical significance of our reported associa We agree with Professor Khuder that one should seek a corre in breast-cancer risk with more direct measures of contact potential exposures to mice, such as local mouse population le or occupational exposures such as in farming (Khuder et al, 19 or in laboratory work with experimental handling of mice (Di et al, 1986). Some areas of the world do have wide fluctuation M. domesticuspopulation levels due to epizootic diseases, climatic variations. One must keep in mind that the MMTV is proposed cause, and that M. domesticuswould be a surrogate o MMTV exposure. The actual risk will depend on the likely mod of MMTV transmission, exposure, and the burden of infecti MMTV in the resident mouse population.

THM Stewart, CA Donnelly, RD Sage, DW Cameron, AFR Ste

REFERENCES

Chie WC, Chen CF, Chen CJ, Chang CL, Liaw YP and Lin RS (1995) Geograph variation of breast cancer in Taiwan: international and migrant comparison Anticancer Res15: 2745–2749

Golovkina TV (2000) A novel mechanism of resistance to mouse mammary tum virus infection. J Virol 74: 2752–2759

Dion AS, Girardi AJ, Williams CC and Pomenti AA (1986) Serologic responses murine mammary tumor virus (MuMTV) in MuMTV-exposed laboratory personnel. J Natl Cancer Inst76: 611–619

Khuder SA, Schaub EA and Keller-Byrne JE (1998) Meta-analyses of non- Hodgkin’s lymphoma and farming. Scand J Work Environ Health24: 255–261

King CM (1982) Age structure and reproduction in feral New Zealand population of the house mouse (Mus musculus), in relation to seedfall of southern beech. New Zealand J Zool9*: 467–480

McCredie M Paul C, Skegg DC and Williams S (1999) Breast cancer in Maori a non-Maori women. Int J Epidemiol28: 189–195

Ross SR, Dzuris JL, Golovkina TV, Clemmons WC and van den Hoogen B (199 Mouse mammary tumor virus (MMTV), a retrovirus that exploits the immun system. Genetics of susceptibility to MMTV infection. Medicina (B Aires)57: 34–42

Stewart TH, Sage RD, Stewart AF and Cameron DW (2000) Breast cancer incid highest in the range of one species of house mouse, Mus domesticus. Br J Cancer82: 446–451

Ursin G Wu AH, Hoover RN, West DW, Nomura AM, Kolonel LN, Pike MC and Ziegler RG (1999) Breast cancer and oral contraceptive use in Asian-Ame women. Am J Epidemiol150: 561–567

References