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Title: Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer
Author: Kraft, Peter
Pharoah, Paul
Chanock, Stephen J.
Albanes, Demetrius
Kolonel, Laurence N.
Hayes, Richard B.
Altshuler, David
Andriole, Gerald
Berg, Christine
Boeing, Heiner
Burtt, Noel P.
Bueno de Mesquita, Bas (Hendrik Bastiaan), 1948-
Calle, Eugenia E.
Cann, Howard
Canzian, Federico
Chen, Yen-Ching
Crawford, David E.
Dunning, Alison M.
Feigelson, Heather S.
Freedman, Matthew L.
Gaziano, John M.
Giovannucci, Ed
González, Carlos Alberto
Haiman, Christopher A.
Hallmans, Goran
Henderson, Brian E.
Hirschhorn, Joel N.
Hunter, David J.
Kaaks, Rudolf
Key, Timothy J.
Le Marchand, Loic
Ma, Jing
Overvad, Kim
Palli, Domenico
Pike, Malcolm C.
Riboli, Elio
Rodriguez, Carmen
Setiawan, Wendy V.
Stampfer, Meir J.
Stram, Daniel O.
Keywords: Càncer de pròstata
Hormones esteroides
Prostate cancer
Steroid hormones
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:
It is part of: PLoS Genetics, 2005, vol. 1, num. 5, p. 0603-0613
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ISSN: 1553-7390
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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