The study of genes is critical for the understanding, diagnosis and treatment of cancer. Some genes predispose individuals to cancer, others are mutated and thereby change a normal cell to a cancer cell, and other genes, because they are expressed in just one kind of cell, can be used to detect very small amounts of cancer that affects that cell type. We have discovered a gene called NKX3.1 that is located at a position on chromosome 8 that is frequently altered in prostate cancer, suggesting that it is a candidate prostate cancer gene. This gene is expressed at high levels in adult prostate tissue and little or not at all in other organs. Lastly, the expression of NKX3.1 is controlled by androgens, male sex hormones that control prostate cancer growth. We found that NKX3.1 is present in two forms that have different levels of activity. One form is present in the majority of the population and a variant form, R52C, is present approximately four times as often in prostate cancer patients than in normal controls. This finding justifies further investigation of the potential role NKX3.1 plays in prostate cancer risk. Because R52C is more active than the normal form of NKX3.1, it may be protective for prostate cancer. We will study three aspects of NKX3.1. We will ask whether the presence of R52C affects risk for getting prostate cancer. We will determine if NKX3.1 is itself a prostate cancer gene because it is mutated in prostate cancer. We will also determine if the prostate-specific nature of NKX3.1 expression can be used to detect microscopic amounts of cancer in patients who appear to be free of disease and therefore if NKX3.1 can be used as a very sensitive test to detect prostate cancer.