Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

Lin, Wei-Yu, Camp, Nicola J., Ghoussaini, Maya, Beesley, Jonathan, Michailidou, Kyriaki, Hopper, John L., Apicella, Carmel, Southey, Melissa C., Stone, Jennifer, Schmidt, Marjanka K., Broeks, Annegien, Van't Veer, Laura J., Rutgers, Emiel J. Th, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, Pornthep, Fasching, Peter A., Haeberle, Lothar, Ekici, Arif B., Beckmann, Matthias W., Peto, Julian, Dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Sawyer, Elinor J., Cheng, Timothy, Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Marme, Frederik, Surowy, Harald M., Burwinkel, Barbara, Guenel, Pascal, Truong, Therese, Menegaux, Florence, Mulot, Claire, Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Benitez, Javier, Zamora, M. Pilar, Arias Perez, Jose Ignacio, Menendez, Primitiva, Gonzalez-Neira, Anna, Pita, Guillermo, Rosario Alonso, M., Alvarez, Nuria, Herrera, Daniel, Anton-Culver, Hoda, Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Stegmaier, Christa, Meindl, Alfons, Lichtner, Peter, Schmutzler, Rita K., Mueller-Myhsok, Bertram, Brauch, Hiltrud, Bruening, Thomas, Ko, Yon-Dschun, Tessier, Daniel C., Vincent, Daniel, Bacot, Francois, Nevanlinna, Heli, Aittomaeki, Kristiina, Blomqvist, Carl, Khan, Sofia, Matsuo, Keitaro, Ito, Hidemi, Iwata, Hiroji, Horio, Akiyo, Bogdanova, Natalia V., Antonenkova, Natalia N., Doerk, Thilo, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Wu, Anna H., Tseng, Chiu-Chen, Van den Berg, David, Stram, Daniel O., Neven, Patrick, Wauters, Els, Wildiers, Hans, Lambrechts, Diether, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Bonanni, Bernardo, Couch, Fergus J., Wang, Xianshu, Vachon, Celine, Purrington, Kristen, Giles, Graham G., Milne, Roger L., Mclean, Catriona, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Simard, Jacques, Goldberg, Mark S., Labreche, France, Dumont, Martine, Teo, Soo Hwang, Yip, Cheng Har, Hassan, Norhashimah, Vithana, Eranga Nishanthie, Kristensen, Vessela, Zheng, Wei, Deming-Halverson, Sandra, Shrubsole, Martha J., Long, Jirong, Winqvist, Robert, Pylkaes, Katri, Jukkola-Vuorinen, Arja, Kauppila, Saila, Andrulis, Irene L., Knight, Julia A., Glendon, Gord, Tchatchou, Sandrine, Devilee, Peter, Tollenaar, Robert A. E. M., Seynaeve, Caroline, Van Asperen, Christi J., Garcia-Closas, Montserrat, Figueroa, Jonine, Lissowska, Jolanta, Brinton, Louise, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Brand, Judith S., Hooning, Maartje J., Hollestelle, Antoinette, Van den Ouweland, Ans M. W., Jager, Agnes, Li, Jingmei, Liu, Jianjun, Humphreys, Keith, Shu, Xiao-Ou, Lu, Wei, Gao, Yu-Tang, Cai, Hui, Cross, Simon S., Reed, Malcolm W. R., Blot, William, Signorello, Lisa B., Cai, Qiuyin, Pharoah, Paul D. P., Perkins, Barbara, Shah, Mitul, Blows, Fiona M., Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Hartman, Mikael, Miao, Hui, Chia, Kee Seng, Putti, Thomas Choudary, Hamann, Ute, Luccarini, Craig, Baynes, Caroline, Ahmed, Shahana, Maranian, Mel, Healey, Catherine S., Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Sangrajrang, Suleeporn, Gaborieau, Valerie, Brennan, Paul, Mckay, James, Slager, Susan, Toland, Amanda E., Yannoukakos, Drakoulis, Shen, Chen-Yang, Hsiung, Chia-Ni, Wu, Pei-Ei, Ding, Shian-ling, Ashworth, Alan, Jones, Michael, Orr, Nick, Swerdlow, Anthony J., Tsimiklis, Helen, Makalic, Enes, Schmidt, Daniel F., Bui, Quang M., Chanock, Stephen J., Hunter, David J., Hein, Rebecca, Dahmen, Norbert, Beckmann, Lars, Aaltonen, Kirsimari, Muranen, Taru A., Heikkinen, Tuomas, Irwanto, Astrid, Rahman, Nazneen, Turnbull, Clare A., Waisfisz, Quinten, Meijers-Heijboer, Hanne E. J., Adank, Muriel A., Van der Luijt, Rob B., Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Easton, Douglas F. and Cox, Angela (2015) Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk. Human Molecular Genetics, 24 1: 285-298. doi:10.1093/hmg/ddu431


Author Lin, Wei-Yu
Camp, Nicola J.
Ghoussaini, Maya
Beesley, Jonathan
Michailidou, Kyriaki
Hopper, John L.
Apicella, Carmel
Southey, Melissa C.
Stone, Jennifer
Schmidt, Marjanka K.
Broeks, Annegien
Van't Veer, Laura J.
Rutgers, Emiel J. Th
Muir, Kenneth
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pornthep
Fasching, Peter A.
Haeberle, Lothar
Ekici, Arif B.
Beckmann, Matthias W.
Peto, Julian
Dos-Santos-Silva, Isabel
Fletcher, Olivia
Johnson, Nichola
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Sawyer, Elinor J.
Cheng, Timothy
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Marme, Frederik
Surowy, Harald M.
Burwinkel, Barbara
Guenel, Pascal
Truong, Therese
Menegaux, Florence
Mulot, Claire
Bojesen, Stig E.
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Benitez, Javier
Zamora, M. Pilar
Arias Perez, Jose Ignacio
Menendez, Primitiva
Gonzalez-Neira, Anna
Pita, Guillermo
Rosario Alonso, M.
Alvarez, Nuria
Herrera, Daniel
Anton-Culver, Hoda
Brenner, Hermann
Dieffenbach, Aida Karina
Arndt, Volker
Stegmaier, Christa
Meindl, Alfons
Lichtner, Peter
Schmutzler, Rita K.
Mueller-Myhsok, Bertram
Brauch, Hiltrud
Bruening, Thomas
Ko, Yon-Dschun
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Nevanlinna, Heli
Aittomaeki, Kristiina
Blomqvist, Carl
Khan, Sofia
Matsuo, Keitaro
Ito, Hidemi
Iwata, Hiroji
Horio, Akiyo
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Doerk, Thilo
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Wu, Anna H.
Tseng, Chiu-Chen
Van den Berg, David
Stram, Daniel O.
Neven, Patrick
Wauters, Els
Wildiers, Hans
Lambrechts, Diether
Chang-Claude, Jenny
Rudolph, Anja
Seibold, Petra
Flesch-Janys, Dieter
Radice, Paolo
Peterlongo, Paolo
Manoukian, Siranoush
Bonanni, Bernardo
Couch, Fergus J.
Wang, Xianshu
Vachon, Celine
Purrington, Kristen
Giles, Graham G.
Milne, Roger L.
Mclean, Catriona
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick
Le Marchand, Loic
Simard, Jacques
Goldberg, Mark S.
Labreche, France
Dumont, Martine
Teo, Soo Hwang
Yip, Cheng Har
Hassan, Norhashimah
Vithana, Eranga Nishanthie
Kristensen, Vessela
Zheng, Wei
Deming-Halverson, Sandra
Shrubsole, Martha J.
Long, Jirong
Winqvist, Robert
Pylkaes, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Andrulis, Irene L.
Knight, Julia A.
Glendon, Gord
Tchatchou, Sandrine
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Van Asperen, Christi J.
Garcia-Closas, Montserrat
Figueroa, Jonine
Lissowska, Jolanta
Brinton, Louise
Czene, Kamila
Darabi, Hatef
Eriksson, Mikael
Brand, Judith S.
Hooning, Maartje J.
Hollestelle, Antoinette
Van den Ouweland, Ans M. W.
Jager, Agnes
Li, Jingmei
Liu, Jianjun
Humphreys, Keith
Shu, Xiao-Ou
Lu, Wei
Gao, Yu-Tang
Cai, Hui
Cross, Simon S.
Reed, Malcolm W. R.
Blot, William
Signorello, Lisa B.
Cai, Qiuyin
Pharoah, Paul D. P.
Perkins, Barbara
Shah, Mitul
Blows, Fiona M.
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Hartman, Mikael
Miao, Hui
Chia, Kee Seng
Putti, Thomas Choudary
Hamann, Ute
Luccarini, Craig
Baynes, Caroline
Ahmed, Shahana
Maranian, Mel
Healey, Catherine S.
Jakubowska, Anna
Lubinski, Jan
Jaworska-Bieniek, Katarzyna
Durda, Katarzyna
Sangrajrang, Suleeporn
Gaborieau, Valerie
Brennan, Paul
Mckay, James
Slager, Susan
Toland, Amanda E.
Yannoukakos, Drakoulis
Shen, Chen-Yang
Hsiung, Chia-Ni
Wu, Pei-Ei
Ding, Shian-ling
Ashworth, Alan
Jones, Michael
Orr, Nick
Swerdlow, Anthony J.
Tsimiklis, Helen
Makalic, Enes
Schmidt, Daniel F.
Bui, Quang M.
Chanock, Stephen J.
Hunter, David J.
Hein, Rebecca
Dahmen, Norbert
Beckmann, Lars
Aaltonen, Kirsimari
Muranen, Taru A.
Heikkinen, Tuomas
Irwanto, Astrid
Rahman, Nazneen
Turnbull, Clare A.
Waisfisz, Quinten
Meijers-Heijboer, Hanne E. J.
Adank, Muriel A.
Van der Luijt, Rob B.
Hall, Per
Chenevix-Trench, Georgia
Dunning, Alison
Easton, Douglas F.
Cox, Angela
Title Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
0964-6906
Publication date 2015-01-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddu431
Open Access Status DOI
Volume 24
Issue 1
Start page 285
End page 298
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
1312 Molecular Biology
Abstract Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 12 Apr 2016, 01:07:02 EST by Matthew Lamb on behalf of School of Medicine