Sex hormones are known to play a role in the development of several human cancers, including those of the female breast, endometrium, ovary, and the male prostate. In addition, there is suggestive evidence implicating sex hormones in other cancers, particularly those of the pancreas, kidney, and brain (glioma, in particular). This evidence includes: 1) the presence of steroid hormone receptors in some of these cancers, 2) sex-related differences in incidence, 3) experimental evidence showing that the development of these cancers can be promoted or inhibited by sex steroid hormones; and 4) use of steroid hormone modulators in the treatment of these diseases. The aims of the present study are to examine whether testosterone, oestradiol, and SHBG are associated with risk of development of these 3 cancers. Little is known about risk factors for cancers of the pancreas, kidney, and brain, all of which are highly fatal. However, to the best of our knowledge, no prospective cohort studies have assessed the association of sex steroid hormone levels (testosterone, estradiol, and sex hormone-binding globulin (SHBG) concentrations with the risk of developing these cancers. The proposed research will contribute to a better understanding of a possible role of sex steroid hormones in the development of these cancers and could lead to new strategies for prevention and treatment. We will use the data on testosterone, oestradiol, and SHBG measurements for all participants in the UK Biobank cohort, excluding those with a previous history of cancer. We will compare sex hormone levels in those who developed the cancers of interest with those in individuals who did not, to determine whether there is a relationship between hormone levels and risk of these cancers. We will examine the association of testosterone, oestradiol, and SHBG with the 3 outcomes. The proposed study will include all participants, male and female, with testosterone, oestradiol, and SHBG measurements but will exclude those with a past history of any cancer (except non-melanoma skin cancer), and also women who reported use of hormone therapy at the time of the sex steroid hormone measurements. The numbers of incident cases of each cancer, as of September 2016, are: pancreas 387; kidney, except renal pelvis - 494; and brain - 302 (we anticipate that the majority of cases will be gliomas). We will use the updated outcomes if this proposal is approved.