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Title: | Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer |
Author: | Kraft, Peter Pharoah, Paul D. P. Chanock, Stephen J. Albanes, Demetrius Kolonel, Laurence N. Hayes, Richard B. Altshuler, David Andriole, Gerald Berg, Christine D. Boeing, Heiner Burtt, Noel P. Bueno de Mesquita, H. Bas Calle, Eugenia E. Cann, Howard Canzian, Federico Chen, Yen-Ching Crawford, David E. Dunning, Alison M. Feigelson, Heather S. Freedman, Matthew L. Gaziano, J. Michael M. Giovannucci, Edward L. González, Carlos Alberto Haiman, Christopher A. Hallmans, Göran Henderson, Brian E. Hirschhorn, Joel N. Hunter, David J. Kaaks, Rudolf Key, Timothy J. Marchand, Loïc Le Ma, Jing Overvad, Kim Palli, Domenico Pike, Malcolm C. Riboli, Elio Rodriguez, Carmen Setiawan, V. Wendy Stampfer, Meir J. Stram, Daniel |
Keywords: | Càncer de pròstata Hormones esteroides Testosterona Prostate cancer Steroid hormones Testosterone |
Issue Date: | 2005 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17β-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Δ5-androsterone-3β,17β-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pgen.0010068 |
It is part of: | PLoS Genetics, 2005, vol. 1, num. 5, p. 0603-0613 |
URI: | http://hdl.handle.net/2445/100707 |
Related resource: | http://dx.doi.org/10.1371/journal.pgen.0010068 |
ISSN: | 1553-7390 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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