- Title
- Association of a common AKAP9 variant with breast cancer risk: a collaborative analysis
- Creator
- Frank, Bernd; Wiestler, Miriam; Australian Breast Cancer Family Study Investigators; Meindl, Alfons; Kiechle, Marion; Slanger, Tracy; Bugert, Peter; Schmutzler, Rita K.; Bartram, Claus R; Flesch-Janys, Dieter; Mutschelknauss, Elke; Ashton, Katie; Kropp, Silke; Salazar, Ramona; Webb, Emily; Hamann, Ute; Brauch, Hiltrud; Justenhoven, Christina; Ko, Yon-Dschun; Brüning, Thomas; dos Santos Silva, Isabel; Johnson, Nichola; Pharoah, Paul P. D.; Hemminki, Kari; Dunning, Alison M.; Pooley, Karen A.; Chang-Claude, Jenny; Easton, Douglas F.; Peto, Julian; Houlston, Richard; Gene Environment Interaction and Breast Cancer in Germany Group; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Investigators; Australian Ovarian Cancer Study Management Group; Chenevix-Trench, Georgia; Spurdle, Amanda B.; Fletcher, Olivia; Burwinkel, Burwinkel; Sutter, Christian; Wappenschmidt, Barbara; Chen, Xiaoqing; Beesley, Jonathan; Hopper, John L.
- Relation
- Journal of the National Cancer Institute Vol. 100, Issue 6, p. 437-442
- Publisher Link
- http://dx.doi.org/10.1093/jnci/djn037
- Publisher
- Oxford University Press
- Resource Type
- journal article
- Date
- 2008
- Description
- 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 13 770 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).
- Subject
- breast cancer; carcinogenesis; A-kinase anchoring proteins (AKAPs); allele
- Identifier
- uon:5128
- Identifier
- http://hdl.handle.net/1959.13/42994
- Identifier
- ISSN:0027-8874
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