title: Association of type 2 diabetes susceptibility variants with advanced prostate cancer risk in the Breast and Prostate Cancer Cohort Consortium.
abstract: Observational studies have found an inverse association between type 2 diabetes (T2D) and prostate cancer (PCa), and genome-wide association studies have found common variants near 3 loci associated with both diseases. The authors examined whether a genetic background that favors T2D is associated with risk of advanced PCa. Data from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium, a genome-wide association study of 2,782 advanced PCa cases and 4,458 controls, were used to evaluate whether individual single nucleotide polymorphisms or aggregations of these 36 T2D susceptibility loci are associated with PCa. Ten T2D markers near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally associated with PCa (P < 0.05); the association for single nucleotide polymorphism rs757210 at the HNF1B locus was significant when multiple comparisons were accounted for (adjusted P = 0.001). Genetic risk scores weighted by the T2D log odds ratio and multilocus kernel tests also indicated a significant relation between T2D variants and PCa risk. A mediation analysis of 9,065 PCa cases and 9,526 controls failed to produce evidence that diabetes mediates the association of the HNF1B locus with PCa risk. These data suggest a shared genetic component between T2D and PCa and add to the evidence for an interrelation between these diseases.
authors.affiliation: Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Machiela
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Ruth
authors.initials: R
authors.lastname: Travis
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
mesh_terms: D001315:Australia / Q000453:epidemiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta