FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation

被引：93

作者：

Udler, Miriam S. ^{[1
,3
]}

Meyer, Kerstin B. ^{[4
]}

Pooley, Karen A. ^{[1
]}

Karlins, Eric ^{[3
]}

Struewing, Jeffery P. ^{[5
]}

Zhang, Jinghui ^{[5
]}

Doody, David R. ^{[6
]}

MacArthur, Stewart ^{[4
]}

Tyrer, Jonathan ^{[2
]}

Pharoah, Paul D. ^{[1
,2
]}

Luben, Robert ^{[1
]}

Bernstein, Leslie ^{[7
]}

Kolonel, Laurence N. ^{[8
]}

Henderson, Brian E. ^{[9
]}

Le Marchand, Loic ^{[9
]}

Ursin, Giske ^{[9
,11
]}

Press, Michael F. ^{[10
]}

Brennan, Paul ^{[12
]}

Sangrajrang, Suleeporn ^{[13
]}

Gaborieau, Valerie ^{[12
]}

Odefrey, Fabrice ^{[12
]}

Shen, Chen-Yang ^{[14
]}

Wu, Pei-Ei ^{[14
]}

Wang, Hui-Chun ^{[14
]}

Kang, Daehee ^{[15
]}

Yoo, Keun-Young ^{[15
]}

Noh, Dong-Young ^{[15
]}

Ahn, Sei-Hyun ^{[16
]}

Ponder, Bruce A. J. ^{[2
,4
]}

Haiman, Christopher A. ^{[9
]}

Malone, Kathleen E. ^{[6
]}

Dunning, Alison M. ^{[2
]}

Ostrander, Elaine A. ^{[3
]}

Easton, Douglas F. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[2] Univ Cambridge, Dept Oncol, Cambridge, England

[3] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA

[4] Li Ka Shing Ctr, CRUK Cambridge Res Inst, Cambridge CB2 0RE, England

[5] US Natl Canc Inst, Lab Populat Genet, Bethesda, MD USA

[6] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[7] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA

[8] Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA

[9] USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA

[10] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA

[11] Univ Oslo, Dept Nutr, Oslo, Norway

[12] Int Agcy Res Canc, F-69372 Lyon, France

[13] Natl Canc Inst, Bangkok, Thailand

[14] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[15] Seoul Natl Univ, Coll Med, Seoul, South Korea

[16] Natl Canc Ctr, Goyang, South Korea

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 09期

关键词：

GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM PATTERNS; GROWTH-FACTOR RECEPTOR-2; MULTIETHNIC COHORT; LOS-ANGELES; WOMEN; SUSCEPTIBILITY; POPULATIONS; GENES; POLYMORPHISM;

D O I：

10.1093/hmg/ddp078

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent, but a causative variant has not yet been conclusively identified. We hypothesized that the weaker linkage disequilibrium across this associated region in populations of African ancestry might help refine the set of candidate-causal single nucleotide polymorphisms (SNPs) previously identified by our group. Eight candidate-causal SNPs were evaluated in 1253 African American invasive BC cases and 1245 controls. A significant association with BC risk was found with SNP rs2981578 (unadjusted per-allele odds ratio = 1.20, 95% confidence interval 1.03-1.41, P-trend = 0.02), with the odds ratio estimate similar to that reported in European and Asian subjects. To extend the fine-mapping, genotype data from the African American studies were analyzed jointly with data from European (n = 7196 cases, 7275 controls) and Asian (n = 3901 cases, 3205 controls) studies. In the combined analysis, SNP rs2981578 was the most strongly associated. Five other SNPs were too strongly correlated to be excluded at a likelihood ratio of < 1/100 relative to rs2981578. Analysis of DNase I hypersensitive sites indicated that only two of these map to highly accessible chromatin, one of which, SNP rs2981578, has previously been implicated in up-regulating FGFR2 expression. Our results demonstrate that the association of SNPs in FGFR2 with BC risk extends to women of African American ethnicity, and illustrate the utility of combining association analysis in datasets of diverse ethnic groups with functional experiments to identify disease susceptibility variants.

引用

页码：1692 / 1703

页数：12

共 22 条

[21] Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women
Ruiz-Narvaez, Edward A.
Rosenberg, Lynn
Yao, Song
Rotimi, Charles N.
Cupples, Adrienne L.
Bandera, Elisa V.
Ambrosone, Christine B.
Adams-Campbell, Lucile L.
Palmer, Julie R.
CARCINOGENESIS, 2013, 34 (02) : 287 - 291
[22] Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women
Rebbeck, Timothy R.
DeMichele, Angela
Tran, Teo V.
Panossian, Saarene
Bunin, Greta R.
Troxel, Andrea B.
Strom, Brian L.
CARCINOGENESIS, 2009, 30 (02) : 269 - 274

← 1 2 3 →