Breast Cancer Susceptibility And Other Risk Factors

An important and largely unresolved question is the relationship between genetic and lifestyle risk factors for breast cancer. The combined analysis by the Collaborative Group examined the effect of several important risk factors on the familial risk of breast cancer, including parity, age at first full-term pregnancy, and ages at menarche and menopause. In each case, they found that the relative risks conferred by these risk factors were similar in women with and without a family history (1). These results imply that such risk factors can be assumed to multiply the familial risks of breast cancer (an assumption made in the Tyrer et al. and Gail models). It also suggests that such risk factors are largely independent of genotype. Whether this is true for specific susceptibility genes, in particular BRCA1 and BRCA2, is less clear however. Several studies have examined the effects of these risk factors in BRCA1/2 carriers but many of the results are contradictory, perhaps reflecting small sample sizes and the difficulty of obtaining unbiased data in high-risk families. There is reasonably convincing evidence that early oophorectomy is protective in carriers, but the effect of parity, for example, is much less clear, with some studies showing a protective effect comparable to that in the general population and other studies showing no effect or even an increased risk (25-29).

Another interesting factor is that some other risk factors for breast cancer themselves have a heritable basis. The most important is mammographic breast density. Twin studies have estimated that approximately 65% of breast density is heritable. Boyd et al (30). have estimated that about 5% to 10% of the familial aggregation of breast cancer is attributable to the breast density (30). Other risk factors that also have a heritable basis include age and menarche, age at menopause, and body mass index.

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