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- Title
Association of a Common AKAP9 Variant With Breast Cancer Risk: A Collaborative Analysis.
- Authors
Frank, Bernd; Wiestler, Miriam; Kropp, Silke; Hemminki, Kari; Spurdle, Amanda B.; Sutter, Christian; Wappenschmidt, Barbara; Xiaoqing Chen; Beesley, Jonathan; Hopper, John L.; Meindl, Alfons; Kiechie, Marion; Slanger, Tracy; Bugert, Peter; Schmutzler, Rita K.; Bartram, Claus R.; Flesch-Janys, Dieter; Mutschelknauss, Elke; Ashton, Katie; Salazar, Ramona
- 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 (M4631, 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 M463l, 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 M4631 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 U (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 U homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10(95% Cl = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% Cl = 1.12 to 1.45, P = .0003) and 1.16 (95% Cl = 1.06 to 1.27, P = .001).
- Subjects
GERMANY; PROTEINS; GENETIC polymorphisms; BREAST cancer risk factors; CARCINOGENESIS; FAMILIAL diseases; CANCER patients
- Publication
JNCI: Journal of the National Cancer Institute, 2008, Vol 100, Issue 6, p437
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djn037