Family history of breast cancer as a determinant of the risk of developing endometrial cancer: a nationwide cohort study.

Despite recent declines in its incidence, endometrial cancer remains the most common cancer of the female reproductive tract in the United States and in the western world. Well established risk factors include exposure to unopposed oestrogen, older age, nulliparity, obesity, and smoking. There are inconsistent reports on the association between endometrial cancer risk and family history of any cancer. Most of the familial studies of endometrial cancer among younger (20-54 years old) women have indicated an association with a family history of endometrial cancer; however, this association among older (55-69 years old) women has been inconsistent. Olson et al showed that neither family history of cancer (for example, endometrium, colon, or breast) overall nor at any specific site was a risk factor in postmenopausal women, whereas Nelson et al reported a significantly higher risk of endometrial cancer among women with a family history of any of the selected sites (that is, uterine, breast, colon, or ovarian cancer). Endometrial cancer and breast cancer share some of the same reproductive and hormonal risk factors, such as nulliparity and exposure to unopposed oestrogen. Reports on double primary cancers in the same person provide further evidence for an aetiological association between breast cancer and endometrial cancer. In addition, it seems likely that there are shared genetic components involved in the aetiology of at least some endometrial and breast cancer cases. Cowden syndrome and hereditary non-polyposis colorectal cancer (HNPCC) are genetic disorders which are said to include a predisposition to both endometrial and breast cancer in genetically at risk family members. However, the familial association between breast and endometrial cancer is uncertain. Lynch et al have identified families in which there are high frequencies of both breast and endometrial cancer. Anderson et al showed a significant excess risk of breast cancer among study participants with a family history of endometrial cancer. On the other hand, Parazzini et al found no association between family history of endometrial cancer in first degree relatives and the risk of breast cancer. In addition, Kelsey et al found no indication of an increased frequency of breast cancer in the first degree female relatives of women with endometrial cancer. To investigate further the hypothesis of an association between family history of breast cancer and the risk of developing endometrial cancer, we analysed data from a large prospective cohort of women with detailed information regarding the number and relationship of relatives affected with breast cancer, their age at breast cancer diagnosis, and breast cancer laterality.