title: Y chromosome haplogroups and prostate cancer in populations of European and Ashkenazi Jewish ancestry.
abstract: Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Hemang
authors.initials: H
authors.lastname: Parikh
authors.forename: Jinping
authors.initials: J
authors.lastname: Jia
authors.forename: Timothy
authors.initials: T
authors.lastname: Myers
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jacobs
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdett
authors.forename: Arpita
authors.initials: A
authors.lastname: Ghosh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.forename: W
authors.initials: W
authors.lastname: Ryan Diver
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: Antoine
authors.initials: A
authors.lastname: Valeri
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Ed
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: J
authors.initials: J
authors.lastname: Michael Gaziano
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Ana
authors.initials: A
authors.lastname: Dutra-Clarke
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhoff
authors.forename: Michael
authors.initials: M
authors.lastname: Alavanja
authors.forename: Laura B
authors.initials: LB
authors.lastname: Freeman
authors.forename: Stella
authors.initials: S
authors.lastname: Koutros
authors.forename: Robert
authors.initials: R
authors.lastname: Hoover
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Ilir
authors.initials: I
authors.lastname: Agalliu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Laufey
authors.initials: L
authors.lastname: Amundadottir
mesh_terms: D001483:Base Sequence; D041322:Chromosomes, Human, Y / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*