title: Association of a common AKAP9 variant with breast cancer risk: a collaborative analysis.
abstract: Data from several studies have suggested that polymorphisms in A-kinase anchoring proteins (AKAPs), which are key components of signal transduction, contribute to carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we genotyped six nonsynonymous single-nucleotide polymorphisms that were predicted to be deleterious and found two (M463I, 1389G>T and N2792S, 8375A>G) to be associated with an allele dose-dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M463I, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M463I with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CI] = 1.08 to 1.27, P = .0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% CI = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI = 1.06 to 1.27, P = .001).
authors.affiliation: Helmholtz-University Group Molecular Epidemiology, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Frank
authors.forename: Miriam
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authors.lastname: Wiestler
authors.forename: Silke
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authors.lastname: Kropp
authors.forename: Kari
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authors.lastname: Hemminki
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Christian
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authors.lastname: Sutter
authors.forename: Barbara
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authors.lastname: Wappenschmidt
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Jonathan
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authors.lastname: Beesley
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Marion
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authors.lastname: Kiechle
authors.forename: Tracy
authors.initials: T
authors.lastname: Slanger
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Dieter
authors.initials: D
authors.lastname: Flesch-Janys
authors.forename: Elke
authors.initials: E
authors.lastname: Mutschelknauss
authors.forename: Katie
authors.initials: K
authors.lastname: Ashton
authors.forename: Ramona
authors.initials: R
authors.lastname: Salazar
authors.forename: Emily
authors.initials: E
authors.lastname: Webb
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Isabel dos Santos
authors.initials: Idos S
authors.lastname: Silva
authors.forename: Nichola
authors.initials: N
authors.lastname: Johnson
authors.forename: Paul P D
authors.initials: PP
authors.lastname: Pharoah
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Karen A
authors.initials: KA
authors.lastname: Pooley
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D001315:Australia / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007532:Isoleucine; D015810:Linkage Disequilibrium; D008715:Methionine; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D003598:Cytoskeletal Proteins; D007532:Isoleucine; D008715:Methionine