Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls

Fletcher, Olivia, Johnson, Nichola, Silva, Isabel dos Santos, Orr, Nick, Ashworth, Alan, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomaki, Kristiina, Blomqvist, Carl, Burwinkel, Barbara, Bartram, Claus R., Meindl, Alfons, Schmutzler, Rita K., Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm W. R., Southey, Melissa C., Smith, Letitia, Spurdle, Amanda B., Hopper, John L., Couch, Fergus J., Olson, Janet E., Wang, Xianshu, Fredericksen, Zachary, Schurmann, Peter, Waltes, Regina, Bremer Michael, Dork,Thilo, Devilee, Peter, van Asperen, Christie J., Tollenaar, Rob A. E. M., Caroline Seynaeve, Hall, Per, Czene, Kamila, Humphreys, Keith, Liu, Jianjun, Ahmed, Shahana, Dunning, Alison M., Maranian, Melanie, Pharoah, Paul D. P., Chenevix-Trench, Georgia, Beesley, Jonathan, Bogdanova, Natalia V., Antonenkova, Natalia N., Zalutsky, Iosif V., Anton-Culver, Hoda, Ziogas, Argyrios, Brauch, Hiltrud, Ko, Yon-Dschun, Hamann, Ute, Fasching, Peter A., Strick, Reiner, Ekici, Arif B., Beckmann, Matthias W., Giles, Graham G., Severi, Gianluca, Baglietto, Laura, English, Dallas R., Milne, Roger L., Benitez, Javier, Arias, Jose Ignacio, Pita, Guillermo, Nordestgaard, Borge G., Bojesen, Stig E., Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong Young, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Garcia-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Brinton, Louise A., Chang-Claude, Jenny, Wang-Gohrke, Shan, Broeks, Annegien, Schmidt, Marjanka K., van Leeuwen, Flora E., Van't Veer, Laura J., Margolin, Sara, Lindblom, Annika, Humphreys, Manjeet K., Morrison, Jonathan, Platte, Radka, Easton, Douglas F. and Peto, Julian (2010) Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls. Cancer Epidemiology, Biomarkers and Prevention, 19 9: 2143-2151. doi:10.1158/1055-9965.EPI-10-0374

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Author Fletcher, Olivia
Johnson, Nichola
Silva, Isabel dos Santos
Orr, Nick
Ashworth, Alan
Nevanlinna, Heli
Heikkinen, Tuomas
Aittomaki, Kristiina
Blomqvist, Carl
Burwinkel, Barbara
Bartram, Claus R.
Meindl, Alfons
Schmutzler, Rita K.
Cox, Angela
Brock, Ian
Elliott, Graeme
Reed, Malcolm W. R.
Southey, Melissa C.
Smith, Letitia
Spurdle, Amanda B.
Hopper, John L.
Couch, Fergus J.
Olson, Janet E.
Wang, Xianshu
Fredericksen, Zachary
Schurmann, Peter
Waltes, Regina
Bremer Michael
Devilee, Peter
van Asperen, Christie J.
Tollenaar, Rob A. E. M.
Caroline Seynaeve
Hall, Per
Czene, Kamila
Humphreys, Keith
Liu, Jianjun
Ahmed, Shahana
Dunning, Alison M.
Maranian, Melanie
Pharoah, Paul D. P.
Chenevix-Trench, Georgia
Beesley, Jonathan
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Zalutsky, Iosif V.
Anton-Culver, Hoda
Ziogas, Argyrios
Brauch, Hiltrud
Ko, Yon-Dschun
Hamann, Ute
Fasching, Peter A.
Strick, Reiner
Ekici, Arif B.
Beckmann, Matthias W.
Giles, Graham G.
Severi, Gianluca
Baglietto, Laura
English, Dallas R.
Milne, Roger L.
Benitez, Javier
Arias, Jose Ignacio
Pita, Guillermo
Nordestgaard, Borge G.
Bojesen, Stig E.
Flyger, Henrik
Kang, Daehee
Yoo, Keun-Young
Noh, Dong Young
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Garcia-Closas, Montserrat
Chanock, Stephen
Lissowska, Jolanta
Brinton, Louise A.
Chang-Claude, Jenny
Wang-Gohrke, Shan
Broeks, Annegien
Schmidt, Marjanka K.
van Leeuwen, Flora E.
Van't Veer, Laura J.
Margolin, Sara
Lindblom, Annika
Humphreys, Manjeet K.
Morrison, Jonathan
Platte, Radka
Easton, Douglas F.
Peto, Julian
Title Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls
Formatted title
Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls
Journal name Cancer Epidemiology, Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
Publication date 2010-09
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-10-0374
Volume 19
Issue 9
Start page 2143
End page 2151
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2011
Language eng
Formatted abstract
Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious.
Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium.
Results: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (Ptrend = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; Ptrend = 0.02).
Conclusions: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer.
Impact: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility. ©2010 AACR.
Keyword Genome-wide association
Susceptibility alleles
Confer susceptibility
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Authors Georgia Chenevix-Trench for the kConFab Investigators and the AOCS Group; Julian Peto for the Breast Cancer Association Consortium; Ute Hamann for the GENICA Consortium

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
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Created: Thu, 31 Mar 2011, 13:15:58 EST by Debbie Banks on behalf of School of Medicine