The Epidemiology of reproductive factors associated with breast cancer and their genetic interactions.

With the use of data from the Utah State Cancer Registry and Utah genealogical data, an epidemiological study of breast cancer patients and their matched controls showed that a late age at the birth of the first child was most strongly associated with incidence of breast cancer. The age at last delivery (ALD) was also associated with breast cancer, with a strong interaction between it and age at first delivery (AFD). The association of AFD with breast cancer incidence was strongest for women with an ALD before 35 years of age and born before 1900, even after adjustment for parity, while the AFD association was strong regardless of ALD for those women born after 1900. Decreased parity was not significantly associated with breast cancer. The genetic effects on AFD were evaluated by restricting the cancer patients to be analyzed to those that were related. This related group was chosen from the relationships that showed an excess number of related pairs compared to the expected number as determined by sets of matched controls. The association of AFD was stronger in this related sample than in the reference sample of unrelated women. The AFD association was also examined in a single large pedigree in which a dominant breast cancer gene is indicated. The women with breast cancer had a first delivery after 26 years of age 6.8 times more often than the unaffected women in the pedigree. There was a suggestion that AFD affected the development of breast cancer in this pedigree and had an additive effect to the presumed genetic mechanism. Finally, it was shown that the risk of incurring a second breast cancer was large compared to other cancers and that the second breast cancer occurred in the opposite breast more often than in the previously affected breast.