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

被引：45

作者：

Frank, Bernd ^{[1
,2
]}

Wiestler, Miriam ^{[1
,2
]}

Kropp, Silke ^{[3
]}

Hemminki, Kari ^{[2
,5
]}

Spurdle, Amanda B. ^{[6
]}

Sutter, Christian ^{[7
]}

Wappenschmidt, Barbara ^{[9
,10
]}

Chen, Xiaoqing ^{[6
]}

Beesley, Jonathan ^{[6
]}

Hopper, John L. ^{[11
]}

Meindl, Alfons ^{[12
]}

Kiechle, Marion ^{[12
]}

Slanger, Tracy ^{[3
]}

Bugert, Peter ^{[8
]}

Schmutzler, Rita K. ^{[9
,10
]}

Bartram, Claus R. ^{[7
]}

Flesch-Janys, Dieter ^{[13
]}

Mutschelknauss, Elke ^{[13
]}

Ashton, Katie ^{[4
]}

Salazar, Ramona ^{[14
]}

Webb, Emily ^{[15
]}

Hamann, Ute ^{[4
]}

Brauch, Hiltrud ^{[17
,18
]}

Justenhoven, Christina ^{[17
,18
]}

Ko, Yon-Dschun ^{[19
]}

Bruening, Thomas ^{[20
]}

Silva, Isabel dos Santos ^{[21
]}

Johnson, Nichola ^{[22
]}

Pharoah, Paul P. D. ^{[23
]}

Dunning, Alison M. ^{[23
]}

Pooley, Karen A. ^{[23
]}

Chang-Claude, Jenny ^{[3
]}

Easton, Douglas F. ^{[24
]}

Peto, Julian ^{[16
,21
]}

Houlston, Richard ^{[15
]}

Chenevix-Trench, Georgia ^{[6
]}

Fletcher, Olivia ^{[22
]}

Burwinkel, Barbara ^{[1
,2
]}

机构：

[1] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Helmholtz Univ Grp Mol Epidemiol, D-69120 Heidelberg, Germany

[2] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany

[3] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[4] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Res Grp Mol Genet Breast Canc, D-69120 Heidelberg, Germany

[5] Karolinska Inst, Ctr Family Med, Huddinge, Sweden

[6] Queensland Inst Med Res, Herston, Qld 4006, Australia

[7] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany

[8] Univ Heidelberg, Fac Mannheim, Red Cross Blood Serv Baden Wurttemberg Hessen, Inst Transfus Med & Immunol, Heidelberg, Germany

[9] Univ Cologne, Ctr Clin, Dept Obstet & Gynaecol, Div Mol Gynaecooncol, Cologne, Germany

[10] Univ Hosp Cologne, Ctr Mol Med Cologne, Cologne, Germany

[11] Univ Melbourne, Ctr Mol Environm & Analyt Epidemiol, Parkville, Vic 3052, Australia

[12] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, D-8000 Munich, Germany

[13] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany

[14] Bioglobe GmbH, Hamburg, Germany

[15] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[16] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England

[17] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany

[18] Univ Tubingen, Stuttgart, Germany

[19] Johanniter Krankenhaus Bonn, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany

[20] Ruhr Univ Bochum, Berufsgenossenschaftliches Forsch Inst Arbeitsmed, Bochum, Germany

[21] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, Canc Res UK Epidemiol & Genet Grp, London WC1, England

[22] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[23] Univ Cambridge, Dept Oncol, Cambridge, England

[24] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England

[25] Peter MacCallum Canc Ctr, Melbourne, Australia

来源：

JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2008年 / 100卷 / 06期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1093/jnci/djn037

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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).

引用

页码：437 / 442

页数：6

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