PMID- 21263130
OWN - NLM
STAT- MEDLINE
DCOM- 20110418
LR  - 20221207
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Linking)
VI  - 103
IP  - 5
DP  - 2011 Mar 2
TI  - Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide 
      association study.
PG  - 425-35
LID - 10.1093/jnci/djq563 [doi]
AB  - BACKGROUND: Genome-wide association studies have identified several common 
      genetic variants associated with breast cancer risk. It is likely, however, that 
      a substantial proportion of such loci have not yet been discovered. METHODS: We 
      compared 296,114 tagging single-nucleotide polymorphisms in 1694 breast cancer 
      case subjects (92% with two primary cancers or at least two affected first-degree 
      relatives) and 2365 control subjects, with validation in three independent series 
      totaling 11,880 case subjects and 12,487 control subjects. Odds ratios (ORs) and 
      associated 95% confidence intervals (CIs) in each stage and all stages combined 
      were calculated using unconditional logistic regression. Heterogeneity was 
      evaluated with Cochran Q and I(2) statistics. All statistical tests were 
      two-sided. RESULTS: We identified a novel risk locus for breast cancer at 9q31.2 
      (rs865686: OR = 0.89, 95% CI = 0.85 to 0.92, P = 1.75 x 10(-10)). This 
      single-nucleotide polymorphism maps to a gene desert, the nearest genes being 
      Kruppel-like factor 4 (KLF4, 636 kb centromeric), RAD23 homolog B (RAD23B, 794 kb 
      centromeric), and actin-like 7A (ACTL7A, 736 kb telomeric). We also identified 
      two variants (rs3734805 and rs9383938) mapping to 6q25.1 estrogen receptor 1 
      (ESR1), which were associated with breast cancer in subjects of northern European 
      ancestry (rs3734805: OR = 1.19, 95% CI = 1.11 to 1.27, P = 1.35 x 10(-7); 
      rs9383938: OR = 1.18, 95% CI = 1.11 to 1.26, P = 1.41 x 10(-7)). A variant 
      mapping to 10q26.13, approximately 300 kb telomeric to the established risk locus 
      within the second intron of FGFR2, was also associated with breast cancer risk, 
      although not at genome-wide statistical significance (rs10510102: OR = 1.12, 95% 
      CI = 1.07 to 1.17, P = 1.58 x 10(-6)). CONCLUSIONS: These findings provide 
      further evidence on the role of genetic variation in the etiology of breast 
      cancer. Fine mapping will be needed to identify causal variants and to determine 
      their functional effects.
FAU - Fletcher, Olivia
AU  - Fletcher O
AD  - Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, 
      UK.
FAU - Johnson, Nichola
AU  - Johnson N
FAU - Orr, Nick
AU  - Orr N
FAU - Hosking, Fay J
AU  - Hosking FJ
FAU - Gibson, Lorna J
AU  - Gibson LJ
FAU - Walker, Kate
AU  - Walker K
FAU - Zelenika, Diana
AU  - Zelenika D
FAU - Gut, Ivo
AU  - Gut I
FAU - Heath, Simon
AU  - Heath S
FAU - Palles, Claire
AU  - Palles C
FAU - Coupland, Ben
AU  - Coupland B
FAU - Broderick, Peter
AU  - Broderick P
FAU - Schoemaker, Minouk
AU  - Schoemaker M
FAU - Jones, Michael
AU  - Jones M
FAU - Williamson, Jill
AU  - Williamson J
FAU - Chilcott-Burns, Sarah
AU  - Chilcott-Burns S
FAU - Tomczyk, Katarzyna
AU  - Tomczyk K
FAU - Simpson, Gemma
AU  - Simpson G
FAU - Jacobs, Kevin B
AU  - Jacobs KB
FAU - Chanock, Stephen J
AU  - Chanock SJ
FAU - Hunter, David J
AU  - Hunter DJ
FAU - Tomlinson, Ian P
AU  - Tomlinson IP
FAU - Swerdlow, Anthony
AU  - Swerdlow A
FAU - Ashworth, Alan
AU  - Ashworth A
FAU - Ross, Gillian
AU  - Ross G
FAU - dos Santos Silva, Isabel
AU  - dos Santos Silva I
FAU - Lathrop, Mark
AU  - Lathrop M
FAU - Houlston, Richard S
AU  - Houlston RS
FAU - Peto, Julian
AU  - Peto J
LA  - eng
GR  - C150/A5660/CRUK_/Cancer Research UK/United Kingdom
GR  - C1178/A3947/CRUK_/Cancer Research UK/United Kingdom
GR  - 076113/WT_/Wellcome Trust/United Kingdom
GR  - BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom
GR  - 085475/WT_/Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110124
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (ACTL7A protein, human)
RN  - 0 (Actins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (KLF4 protein, human)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (RAD23B protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
SB  - IM
MH  - Actins/genetics
MH  - Adult
MH  - Aged
MH  - Breast Neoplasms/ethnology/*genetics
MH  - Case-Control Studies
MH  - Chromosomes, Human, Pair 10
MH  - Chromosomes, Human, Pair 6
MH  - *Chromosomes, Human, Pair 9
MH  - DNA Repair Enzymes/genetics
MH  - DNA-Binding Proteins/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/genetics
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Middle Aged
MH  - Odds Ratio
MH  - *Polymorphism, Single Nucleotide
MH  - Quality Control
MH  - Risk Factors
MH  - Surveys and Questionnaires
MH  - United Kingdom
MH  - White People/*genetics
EDAT- 2011/01/26 06:00
MHDA- 2011/04/19 06:00
CRDT- 2011/01/26 06:00
PHST- 2011/01/26 06:00 [entrez]
PHST- 2011/01/26 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
AID - djq563 [pii]
AID - 10.1093/jnci/djq563 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2011 Mar 2;103(5):425-35. doi: 10.1093/jnci/djq563. Epub 2011 
      Jan 24.