Genetic variation in the HSD17B1 gene and risk of prostate cancer.

PLoS Genetics. 2005;1(5):e68 DOI 10.1371/journal.pgen.0010068

 

Journal Homepage

Journal Title: PLoS Genetics

ISSN: 1553-7390 (Print); 1553-7404 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Science: Biology (General): Genetics

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS

Peter Kraft
Paul Pharoah
Stephen J Chanock
Demetrius Albanes
Laurence N Kolonel
Richard B Hayes
David Altshuler
Gerald Andriole
Christine Berg
Heiner Boeing
Noel P Burtt
Bas Bueno-de-Mesquita
Eugenia E Calle
Howard Cann
Federico Canzian
Yen-Ching Chen
David E Crawford
Alison M Dunning
Heather S Feigelson
Matthew L Freedman
John M Gaziano
Ed Giovannucci
Carlos Alberto Gonzalez
Christopher A Haiman
Goran Hallmans
Brian E Henderson
Joel N Hirschhorn
David J Hunter
Rudolf Kaaks
Timothy Key
Loic Le Marchand
Jing Ma
Kim Overvad
Domenico Palli
Malcolm C Pike
Elio Riboli
Carmen Rodriguez
Wendy V Setiawan
Meir J Stampfer
Daniel O Stram
Gilles Thomas
Michael J Thun
Ruth Travis
Antonia Trichopoulou
Jarmo Virtamo
Sholom Wacholder

EDITORIAL INFORMATION

Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 26 weeks

 

Abstract | Full Text

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 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-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.