Twin Studies and Bilateral Breast Cancer

In principle, the familial aggregation of breast cancer may be due either to genetic factors or to lifestyle or environmental factors that are shared among relatives. The latter possibility is unlikely in that no lifestyle risk factors that are sufficiently strong to materially affect familial aggregation of the disease have been identified. More formal evidence that familial aggregation has a genetic basis comes from twin studies. Based on an analysis of population-based twin registers from the Nordic studies, Lichtenstein et al. (23) found that the risk of breast cancer in the monozygotic (MZ) twins of cases was about twice as great as the risk in the dizygotic (DZ) twins. Using a particular multifactorial model, this study estimated that about 27% of the variation in breast cancer risk was genetic. This particular estimate should be viewed cautiously since it does depend on the model used and on how one defines the variation in breast cancer risk, but it does point to a substantial genetic component.

This evidence of a higher risk of the disease in MZ twins of cases was supported by the study of Peto and Mack (24), who estimated that the risk of breast cancer in the MZ twins of cases was 1.4% per annum. They noted that this risk was approximately twice the incidence rate of contralateral breast cancer in affected women. This is consistent with the hypothesis that the increased risk of a second breast cancer is primarily due to genetic susceptibility, but with only one breast at risk. Peto and Mack also hypothesized that the relative constancy in the risk of contralateral breast cancer might imply that much of breast cancer occurred in women who had reached a high risk of the disease, and that genetic susceptibility might effect the age at which women became high risk rather than (as in more standard models of susceptibility) the actual risk of the disease.

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