Identification of novel genetic markers of breast cancer survival
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Identification of novel genetic markers of breast cancer survival. / Guo, Qi; Schmidt, Marjanka K; Kraft, Peter; Canisius, Sander; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Kar, Siddhartha; Beesley, Jonathan; Dunning, Alison M; Shah, Mitul; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Lambrechts, Diether; Weltens, Caroline; Leunen, Karin; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Blomqvist, Carl; Aittomäki, Kristiina; Fagerholm, Rainer; Muranen, Taru A; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Broeks, Annegien; Hogervorst, Frans B; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; kConFab Investigators.
In: National Cancer Institute. Journal (Online), Vol. 107, No. 5, 5, 05.2015, p. 1-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of novel genetic markers of breast cancer survival
AU - Guo, Qi
AU - Schmidt, Marjanka K
AU - Kraft, Peter
AU - Canisius, Sander
AU - Chen, Constance
AU - Khan, Sofia
AU - Tyrer, Jonathan
AU - Bolla, Manjeet K
AU - Wang, Qin
AU - Dennis, Joe
AU - Michailidou, Kyriaki
AU - Lush, Michael
AU - Kar, Siddhartha
AU - Beesley, Jonathan
AU - Dunning, Alison M
AU - Shah, Mitul
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Eriksson, Mikael
AU - Lambrechts, Diether
AU - Weltens, Caroline
AU - Leunen, Karin
AU - Bojesen, Stig E
AU - Nordestgaard, Børge G
AU - Nielsen, Sune F
AU - Flyger, Henrik
AU - Chang-Claude, Jenny
AU - Rudolph, Anja
AU - Seibold, Petra
AU - Flesch-Janys, Dieter
AU - Blomqvist, Carl
AU - Aittomäki, Kristiina
AU - Fagerholm, Rainer
AU - Muranen, Taru A
AU - Couch, Fergus J
AU - Olson, Janet E
AU - Vachon, Celine
AU - Andrulis, Irene L
AU - Knight, Julia A
AU - Glendon, Gord
AU - Mulligan, Anna Marie
AU - Broeks, Annegien
AU - Hogervorst, Frans B
AU - Haiman, Christopher A
AU - Henderson, Brian E
AU - Schumacher, Fredrick
AU - Le Marchand, Loic
AU - Hopper, John L
AU - Tsimiklis, Helen
AU - Apicella, Carmel
AU - kConFab Investigators
N1 - © The Author 2015. Published by Oxford University Press.
PY - 2015/5
Y1 - 2015/5
N2 - BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival.METHODS: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided.RESULTS: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust.CONCLUSIONS: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.
AB - BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival.METHODS: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided.RESULTS: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust.CONCLUSIONS: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.
KW - Breast Neoplasms
KW - European Continental Ancestry Group
KW - Female
KW - Genetic Markers
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Prognosis
KW - Receptors, Estrogen
KW - Survival Analysis
U2 - 10.1093/jnci/djv081
DO - 10.1093/jnci/djv081
M3 - Journal article
C2 - 25890600
VL - 107
SP - 1
EP - 9
JO - National Cancer Institute. Journal (Online)
JF - National Cancer Institute. Journal (Online)
SN - 1460-2105
IS - 5
M1 - 5
ER -
ID: 159082276