Identification of Y chromosomes associated with risk for prostate cancer. L. A. Cannon-Albright1,2, J. M. Farnham1, C. C. Teerlink1, R. A. Stephenson1,2,3 1) University of Utah School of Medicine, Salt Lake City, UT; 2) George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT; 3) Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT.
Published evidence suggests that genes present on the Y chromosome may be involved in increased risk for prostate cancer; however, the Y chromosome has received little attention in previous genetic studies of prostate cancer. An analysis of the computerized Utah Population Database (UPDB) genealogy of the Utah pioneers linked to statewide cancer data was used to test the hypothesis of a role of the Y chromosome in prostate cancer predisposition. Analysis was limited to the 1.25 million individuals in the UPDB genealogy who have at least 12 of their 14 immediate ancestors. Within the UPDB we identified all males with no father in the genealogy data (founders) and assigned them each a unique, sequential Y chromosome id (YID); each of their male descendants, and all of his male descendants, and so forth, were assigned this same YID, effectively identifying each independent Y chromosome in the UPDB. We identified 257,252 YIDs for which there were at least 2 males who shared each Y chromosome. The largest YID group included 2264 males. All YIDs were assumed to be distinct based on genealogy data. We estimated rates of prostate cancer for the population of 1.25 million individuals in the UPDB using birth year and birth state (Utah or not) cohorts and using the Utah Cancer SEER registry to identify cases. These rates were applied to all males in each YID group to estimate the number of prostate cancer cases expected. We tested these 1000 independent sets of males, each hypothesized to share the same Y chromosome, for a significant excess of prostate cancer. In these 1000 sets of between 167 and 2264 males sharing a Y chromosome we identified multiple Y chromosomes associated with a significant excess risk for prostate cancer (p<0.05/1000 correction for multiple testing). An example Y chromosome group of interest includes a total of 9750 total male descendants of the YID founder; there were a total of 65 prostate cancer cases among all the male descendants (45.6 expected; p=0.005); there were a total of 498 males sharing the Y chromosome of the Y group founder with 26 prostate cancer cases observed (9.5 expected, p=8E-6). Among the male descendants who did not share the Y chromosome of the founder there were 39 prostate cancer cases observed, with 36.1 expected (p=0.68). These results show strong support for a role of specific Y-chromosomes in prostate cancer predisposition and identify a powerful resource for identifying the genes or variants responsible.
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