Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25

被引：107

作者：

Fejerman, Laura ^{[1
]}

Ahmadiyeh, Nasim ^{[2
]}

Hu, Donglei ^{[1
]}

Huntsman, Scott ^{[1
]}

Beckman, Kenneth B. ^{[3
]}

Caswell, Jennifer L. ^{[1
]}

Tsung, Karen ^{[2
]}

John, Esther M. ^{[4
,5
]}

Torres-Mejia, Gabriela ^{[6
]}

Carvajal-Carmona, Luis ^{[7
,8
]}

Echeverry, Maria Magdalena ^{[7
]}

Tuazon, Anna Marie D. ^{[7
]}

Ramirez, Carolina ^{[8
]}

Gignoux, Christopher R. ^{[9
]}

Eng, Celeste ^{[10
]}

Gonzalez-Burchard, Esteban ^{[10
]}

Henderson, Brian ^{[11
]}

Le Marchand, Loic ^{[12
]}

Kooperberg, Charles ^{[13
]}

Hou, Lifang ^{[14
]}

Agalliu, Ilir ^{[15
]}

Kraft, Peter ^{[16
]}

Lindstroem, Sara ^{[16
]}

Perez-Stable, Eliseo J. ^{[1
]}

Haiman, Christopher A. ^{[11
]}

Ziv, Elad ^{[1
]}

机构：

[1] Univ Calif San Francisco, Inst Human Genet, Dept Med, Div Gen Internal Med, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94122 USA

[3] Univ Minnesota, Genom Ctr, Minneapolis, MN 55455 USA

[4] Canc Prevent Inst Calif, Fremont, CA 94538 USA

[5] Stanford Univ, Sch Med, Stanford Canc Inst, Dept Hlth Res & Policy,Div Epidemiol, Palo Alto, CA 94305 USA

[6] Natl Inst Publ Hlth, Cuernavaca 62100, Morelos, Mexico

[7] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA

[8] Univ Tolima, Res Grp, Ibague 7652000, Colombia

[9] Stanford Univ, Dept Genet, Palo Alto, CA 94305 USA

[10] Univ Calif San Francisco, Inst Human Genet, Dept Med, Div Pulm & Crit Care, San Francisco, CA 94158 USA

[11] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA

[12] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA

[13] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[14] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Dept Prevent Med, Chicago, IL 60611 USA

[15] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA

[16] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

美国国家卫生研究院;

关键词：

BRCA1 MUTATION CARRIERS; MAMMOGRAPHIC DENSITY; SUSCEPTIBILITY LOCUS; GENETIC ANCESTRY; COMMON VARIANTS; RISK VARIANT; POPULATION; FRAMEWORK; ADMIXTURE; ALLELES;

D O I：

10.1038/ncomms6260

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 50 of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P = 9 x 10(-18)), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21-0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49-0.80; P heterogeneity = 0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P = 0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations.

引用

页数：8

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