Association of a Common AKAP9 Variant With Breast Cancer Risk: A Collaborative Analysis

J Natl Cancer Inst. 2008 Mar 19;100(6):437-42. doi: 10.1093/jnci/djn037. Epub 2008 Mar 11.

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).

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • A Kinase Anchor Proteins / genetics*
  • Adult
  • Aged
  • Alleles
  • Australia / epidemiology
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Cytoskeletal Proteins / genetics*
  • Europe / epidemiology
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • Germany / epidemiology
  • Humans
  • Isoleucine
  • Linkage Disequilibrium
  • Methionine
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Research Design
  • Risk Assessment
  • Risk Factors

Substances

  • A Kinase Anchor Proteins
  • AKAP9 protein, human
  • Cytoskeletal Proteins
  • Isoleucine
  • Methionine