PMID- 22228098
OWN - NLM
STAT- MEDLINE
DCOM- 20120618
LR  - 20221207
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 21
IP  - 8
DP  - 2012 Apr 15
TI  - Admixture mapping identifies a locus on 6q25 associated with breast cancer risk 
      in US Latinas.
PG  - 1907-17
LID - 10.1093/hmg/ddr617 [doi]
AB  - Among US Latinas and Mexican women, those with higher European ancestry have 
      increased risk of breast cancer. We combined an admixture mapping and genome-wide 
      association mapping approach to search for genomic regions that may explain this 
      observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 
      1272) were genotyped using Affymetrix and Illumina arrays. We inferred 
      locus-specific genetic ancestry and compared the ancestry between cases and 
      controls. We also performed single nucleotide polymorphism (SNP) association 
      analyses in regions of interest. Correction for multiple-hypothesis testing was 
      conducted using permutations (P(corrected)). We identified one region where 
      genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds 
      ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 
      0.65-0.85, P= 1.1 x 10(-5), P(corrected)= 0.02]. A second region on 11p15 showed 
      a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 
      0.68-0.87, P= 4.3 x 10(-5), P(corrected)= 0.08). In both regions, breast cancer 
      risk decreased with higher Indigenous American ancestry in concordance with 
      observations made on global ancestry. The peak of the 6q25 signal includes the 
      estrogen receptor 1 (ESR1) gene and 5' region, a locus previously implicated in 
      breast cancer. Genome-wide association analysis found that a multi-SNP model 
      explained the admixture signal in both regions. Our results confirm that the 
      association between genetic ancestry and breast cancer risk in US Latinas is 
      partly due to genetic differences between populations of European and Indigenous 
      Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will 
      lead to the discovery of the biologically functional variant/s behind this 
      association.
FAU - Fejerman, Laura
AU  - Fejerman L
AD  - Department of Medicine, Division of General Internal Medicine, Institute for 
      Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of 
      California San Francisco, San Francisco, CA 94158, USA.
FAU - Chen, Gary K
AU  - Chen GK
FAU - Eng, Celeste
AU  - Eng C
FAU - Huntsman, Scott
AU  - Huntsman S
FAU - Hu, Donglei
AU  - Hu D
FAU - Williams, Amy
AU  - Williams A
FAU - Pasaniuc, Bogdan
AU  - Pasaniuc B
FAU - John, Esther M
AU  - John EM
FAU - Via, Marc
AU  - Via M
FAU - Gignoux, Christopher
AU  - Gignoux C
FAU - Ingles, Sue
AU  - Ingles S
FAU - Monroe, Kristine R
AU  - Monroe KR
FAU - Kolonel, Laurence N
AU  - Kolonel LN
FAU - Torres-Mejia, Gabriela
AU  - Torres-Mejia G
FAU - Perez-Stable, Eliseo J
AU  - Perez-Stable EJ
FAU - Burchard, Esteban Gonzalez
AU  - Burchard EG
FAU - Henderson, Brian E
AU  - Henderson BE
FAU - Haiman, Christopher A
AU  - Haiman CA
FAU - Ziv, Elad
AU  - Ziv E
LA  - eng
GR  - CA160607/CA/NCI NIH HHS/United States
GR  - AI077439/AI/NIAID NIH HHS/United States
GR  - HL078885/HL/NHLBI NIH HHS/United States
GR  - 5K12HD052163/HD/NICHD NIH HHS/United States
GR  - U01 CA078296/CA/NCI NIH HHS/United States
GR  - R25 CA112355/CA/NCI NIH HHS/United States
GR  - R01-CA77305/CA/NCI NIH HHS/United States
GR  - R01 CA63464/CA/NCI NIH HHS/United States
GR  - R01-63446/PHS HHS/United States
GR  - HL088133/HL/NHLBI NIH HHS/United States
GR  - K01 CA160607/CA/NCI NIH HHS/United States
GR  - R01 ES015794/ES/NIEHS NIH HHS/United States
GR  - R01 CA132839/CA/NCI NIH HHS/United States
GR  - U01 CA69417/CA/NCI NIH HHS/United States
GR  - R37 CA54281/CA/NCI NIH HHS/United States
GR  - R01 HG006399/HG/NHGRI NIH HHS/United States
GR  - R01 CA120120/CA/NCI NIH HHS/United States
GR  - K24 CA169004/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120106
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (LSP1 protein, human)
RN  - 0 (Microfilament Proteins)
SB  - IM
MH  - Breast Neoplasms/classification/*genetics
MH  - Case-Control Studies
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Estrogen Receptor alpha/*genetics
MH  - Female
MH  - Gene Frequency
MH  - *Genetic Loci
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Hispanic or Latino/*genetics
MH  - Humans
MH  - Microfilament Proteins/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - White People/genetics
PMC - PMC3313799
EDAT- 2012/01/10 06:00
MHDA- 2012/06/19 06:00
PMCR- 2013/04/15
CRDT- 2012/01/10 06:00
PHST- 2012/01/10 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/06/19 06:00 [medline]
PHST- 2013/04/15 00:00 [pmc-release]
AID - ddr617 [pii]
AID - 10.1093/hmg/ddr617 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2012 Apr 15;21(8):1907-17. doi: 10.1093/hmg/ddr617. Epub 2012 Jan 
      6.