title: Genetic variation in the HSD17B1 gene and risk of prostate cancer.
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 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.
authors.affiliation: Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Paul
authors.initials: P
authors.lastname: Pharoah
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.forename: Christine
authors.initials: C
authors.lastname: Berg
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Noel P
authors.initials: NP
authors.lastname: Burtt
authors.forename: Bas
authors.initials: B
authors.lastname: Bueno-de-Mesquita
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Howard
authors.initials: H
authors.lastname: Cann
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: David E
authors.initials: DE
authors.lastname: Crawford
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Heather S
authors.initials: HS
authors.lastname: Feigelson
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Freedman
authors.forename: John M
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Ed
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Gonzalez
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Goran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Timothy
authors.initials: T
authors.lastname: Key
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Wendy V
authors.initials: WV
authors.lastname: Setiawan
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Ruth
authors.initials: R
authors.lastname: Travis
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D012306:Risk; D012307:Risk Factors
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase