A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age
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A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age. / Ahsan, Habibul; Halpern, Jerry; Kibriya, Muhammad G; Pierce, Brandon L; Tong, Lin; Gamazon, Eric; McGuire, Valerie; Felberg, Anna; Shi, Jianxin; Jasmine, Farzana; Roy, Shantanu; Brutus, Rachelle; Argos, Maria; Melkonian, Stephanie; Chang-Claude, Jenny; Andrulis, Irene; Hopper, John L; John, Esther M; Malone, Kathi; Ursin, Giske; Gammon, Marilie D; Thomas, Duncan C; Seminara, Daniela; Casey, Graham; Knight, Julia A; Southey, Melissa C; Giles, Graham G; Santella, Regina M; Lee, Eunjung; Conti, David; Duggan, David; Gallinger, Steve; Haile, Robert; Jenkins, Mark; Lindor, Noralane M; Newcomb, Polly; Michailidou, Kyriaki; Apicella, Carmel; Park, Daniel J; Peto, Julian; Fletcher, Olivia; dos Santos Silva, Isabel; Lathrop, Mark; Hunter, David J; Chanock, Stephen J; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lochmann, Magdalena; Beckmann, Lars; Hein, Rebecca; Makalic, Enes; Schmidt, Daniel F; Bui, Quang Minh; Stone, Jennifer; Flesch-Janys, Dieter; Dahmen, Norbert; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Rahman, Nazneen; Turnbull, Clare; Dunning, Alison M; Pharoah, Paul; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Nicolae, Dan; Easton, Douglas F; Cox, Nancy J; Whittemore, Alice S; Familial Breast Cancer Study.
In: CANCER EPIDEM BIOMAR, Vol. 23, No. 4, 01.04.2014, p. 658-69.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age
AU - Ahsan, Habibul
AU - Halpern, Jerry
AU - Kibriya, Muhammad G
AU - Pierce, Brandon L
AU - Tong, Lin
AU - Gamazon, Eric
AU - McGuire, Valerie
AU - Felberg, Anna
AU - Shi, Jianxin
AU - Jasmine, Farzana
AU - Roy, Shantanu
AU - Brutus, Rachelle
AU - Argos, Maria
AU - Melkonian, Stephanie
AU - Chang-Claude, Jenny
AU - Andrulis, Irene
AU - Hopper, John L
AU - John, Esther M
AU - Malone, Kathi
AU - Ursin, Giske
AU - Gammon, Marilie D
AU - Thomas, Duncan C
AU - Seminara, Daniela
AU - Casey, Graham
AU - Knight, Julia A
AU - Southey, Melissa C
AU - Giles, Graham G
AU - Santella, Regina M
AU - Lee, Eunjung
AU - Conti, David
AU - Duggan, David
AU - Gallinger, Steve
AU - Haile, Robert
AU - Jenkins, Mark
AU - Lindor, Noralane M
AU - Newcomb, Polly
AU - Michailidou, Kyriaki
AU - Apicella, Carmel
AU - Park, Daniel J
AU - Peto, Julian
AU - Fletcher, Olivia
AU - dos Santos Silva, Isabel
AU - Lathrop, Mark
AU - Hunter, David J
AU - Chanock, Stephen J
AU - Meindl, Alfons
AU - Schmutzler, Rita K
AU - Müller-Myhsok, Bertram
AU - Lochmann, Magdalena
AU - Beckmann, Lars
AU - Hein, Rebecca
AU - Makalic, Enes
AU - Schmidt, Daniel F
AU - Bui, Quang Minh
AU - Stone, Jennifer
AU - Flesch-Janys, Dieter
AU - Dahmen, Norbert
AU - Nevanlinna, Heli
AU - Aittomäki, Kristiina
AU - Blomqvist, Carl
AU - Hall, Per
AU - Czene, Kamila
AU - Irwanto, Astrid
AU - Liu, Jianjun
AU - Rahman, Nazneen
AU - Turnbull, Clare
AU - Dunning, Alison M
AU - Pharoah, Paul
AU - Waisfisz, Quinten
AU - Meijers-Heijboer, Hanne
AU - Uitterlinden, Andre G
AU - Rivadeneira, Fernando
AU - Nicolae, Dan
AU - Easton, Douglas F
AU - Cox, Nancy J
AU - Whittemore, Alice S
AU - Familial Breast Cancer Study
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.
AB - Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.
KW - Breast Neoplasms
KW - Case-Control Studies
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Middle Aged
KW - Phosphofructokinase-1, Muscle Type
KW - Polymorphism, Single Nucleotide
KW - Tumor Markers, Biological
U2 - 10.1158/1055-9965.EPI-13-0340
DO - 10.1158/1055-9965.EPI-13-0340
M3 - SCORING: Journal article
C2 - 24493630
VL - 23
SP - 658
EP - 669
JO - CANCER EPIDEM BIOMAR
JF - CANCER EPIDEM BIOMAR
SN - 1055-9965
IS - 4
ER -