Association of a common AKAP9 variant with breast cancer risk: A collaborative analysis

作者：Frank Bernd; Wiestler Miriam; Kropp Silke; Hemminki Kari; Spurdle Amanda B; Sutter Christian; Wappenschmidt Barbara; Chen Xiaoqing; Beesley Jonathan; Hopper John L; Meindl Alfons; Kiechle Marion; Slanger Tracy; Bugert Peter; Schmutzler Rita K; Bartram Claus R; Flesch Janys Dieter; Mutschelknauss Elke; Ashton Katie; Salazar Ramona; Webb Emily; Hamann Ute; Brauch Hiltrud; Justenhoven Christina; Ko Yon Dschun; Bruening Thomas; Silva Isabel dos Santos

来源：JNCI-Journal of the National Cancer Institute, 2008, 100(6): 437-442.

DOI：10.1093/jnci/djn037

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 sing le-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 M4631, 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 TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CL] = 1.08 to 1.27, P =.0003), and the OR for TT 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).

• 出版日期2008-3-19
• 单位河北医科大学