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

Laura Fejerman; Nasim Ahmadiyeh; Donglei Hu; Scott Huntsman; Kenneth B. Beckman; Jennifer L. Caswell; Karen Tsung; Esther M. John; Gabriela Torres-Mejia; Luis Carvajal-Carmona; María Magdalena Echeverry; Anna Marie D. Tuazon; Carolina Ramirez; Mabel Elena Bohórquez; Rodrigo Prieto; Ángel Criollo; Carolina Ramírez; Ana Patricia Estrada; John Jairo Suáres; Gilbert Mateus; Jorge Mario Castro; Yesid Sánchez; Raúl Murillo; Martha Lucia Serrano; Carolina Sanabria; Justo Germán Olaya; Alejandro Vélez; Jenny Andrea Carmona; Nancy Guerrero Rodríguez; Cristina Serón Sousa; Cesar Eduardo Alvarez Mendez; Ana Isabel Orduz Galviz; Christopher R. Gignoux; Celeste Eng; Esteban Gonzalez-Burchard; Brian Henderson; Loic Le Marchand; Charles Kooperberg; Lifang Hou; Ilir Agalliu; Peter Kraft; Sara Lindström; Eliseo J. Perez-Stable; Christopher A. Haiman; Elad Ziv

doi:10.1038/ncomms6260

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

Laura Fejerman, Nasim Ahmadiyeh, Donglei Hu, Scott Huntsman, Kenneth B. Beckman, Jennifer L. Caswell, Karen Tsung, Esther M. John, Gabriela Torres-Mejia, Luis Carvajal-Carmona, María Magdalena Echeverry, Anna Marie D. Tuazon, Carolina Ramirez, Mabel Elena Bohórquez, Rodrigo Prieto, Ángel Criollo, Carolina Ramírez, Ana Patricia Estrada, John Jairo Suáres, Gilbert MateusJorge Mario Castro, Yesid Sánchez, Raúl Murillo, Martha Lucia Serrano, Carolina Sanabria, Justo Germán Olaya, Alejandro Vélez, Jenny Andrea Carmona, Nancy Guerrero Rodríguez, Cristina Serón Sousa, Cesar Eduardo Alvarez Mendez, Ana Isabel Orduz Galviz, Christopher R. Gignoux, Celeste Eng, Esteban Gonzalez-Burchard, Brian Henderson, Loic Le Marchand, Charles Kooperberg, Lifang Hou, Ilir Agalliu, Peter Kraft, Sara Lindström, Eliseo J. Perez-Stable, Christopher A. Haiman^*, Elad Ziv

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

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Abstract

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 5′ 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 × 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.

Original language	English (US)
Article number	5260
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6260
State	Published - Oct 20 2014

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms6260

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Fejerman, L., Ahmadiyeh, N., Hu, D., Huntsman, S., Beckman, K. B., Caswell, J. L., Tsung, K., John, E. M., Torres-Mejia, G., Carvajal-Carmona, L., Echeverry, M. M., Tuazon, A. M. D., Ramirez, C., Bohórquez, M. E., Prieto, R., Criollo, Á., Ramírez, C., Estrada, A. P., Suáres, J. J., ... Ziv, E. (2014). Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25. Nature communications, 5, [5260]. https://doi.org/10.1038/ncomms6260

@article{ee929d1212534a9da933a5b41470bb34,

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

abstract = "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 5′ 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 × 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.",

author = "Laura Fejerman and Nasim Ahmadiyeh and Donglei Hu and Scott Huntsman and Beckman, {Kenneth B.} and Caswell, {Jennifer L.} and Karen Tsung and John, {Esther M.} and Gabriela Torres-Mejia and Luis Carvajal-Carmona and Echeverry, {Mar{\'i}a Magdalena} and Tuazon, {Anna Marie D.} and Carolina Ramirez and Boh{\'o}rquez, {Mabel Elena} and Rodrigo Prieto and {\'A}ngel Criollo and Carolina Ram{\'i}rez and Estrada, {Ana Patricia} and Su{\'a}res, {John Jairo} and Gilbert Mateus and Castro, {Jorge Mario} and Yesid S{\'a}nchez and Ra{\'u}l Murillo and {Lucia Serrano}, Martha and Carolina Sanabria and Olaya, {Justo Germ{\'a}n} and Alejandro V{\'e}lez and Carmona, {Jenny Andrea} and Rodr{\'i}guez, {Nancy Guerrero} and {Ser{\'o}n Sousa}, Cristina and Mendez, {Cesar Eduardo Alvarez} and Galviz, {Ana Isabel Orduz} and Gignoux, {Christopher R.} and Celeste Eng and Esteban Gonzalez-Burchard and Brian Henderson and Marchand, {Loic Le} and Charles Kooperberg and Lifang Hou and Ilir Agalliu and Peter Kraft and Sara Lindstr{\"o}m and Perez-Stable, {Eliseo J.} and Haiman, {Christopher A.} and Elad Ziv",

note = "Funding Information: We want to thank the study participants. This work was supported by the National Cancer Institute (K01 CA160607 to L.F., R01 CA120120 and K24 CA169004 to E.Z. and R01 CA132839 to C.A.H.), the Center for Aging in Diverse Communities (CADC) under the Resource Centers for Minority Aging Research programme by the National Institute on Aging (P30-AG15272) and the National Cancer Institute grant from the Special Population Network programme to the University of Texas, San Antonio (Redes En Acci{\'o}n no. U01CA86117). The San Francisco Bay Area Breast Cancer Study was supported by the National Cancer Institute (CA63446 and CA77305), the US Department of Defense (DAMD17-96-1-6071) and the California Breast Cancer Research Program (7PB-0068). The Northern California Breast Cancer Family Registry was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The Multiethnic Cohort Study was supported by the National Institutes of Health grants R01 CA63464 and R37 CA54281, R01 CA132839, 5UM1CA164973. The GALA1 study was supported by The National Institutes of Health (HL078885, AI077439 and HL088133). The Mexico Breast Cancer Study was funded by Consejo Nacional de Ciencia y Tecnolog{\'i}a (SALUD-2002-C01-7462). The COLUMBUS study receives support from GSK Oncology (Ethnic Research Initiative), University of Tolima, University of California Davis and The V Foundation. L.C.-C. is a V Foundation V Scholar. A.M.D.T. is supported by the Howard Hughes Medical Institute, Integrating Medicine into Basic Science fellowship. The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. Genotyping of MEC samples was also supported by the Slim Initiative in Genomic Medicine for the Americas (SIGMA), a joint US–Mexico project funded by the Carlos Slim Health Institute. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",

year = "2014",

month = oct,

day = "20",

doi = "10.1038/ncomms6260",

language = "English (US)",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Fejerman, L, Ahmadiyeh, N, Hu, D, Huntsman, S, Beckman, KB, Caswell, JL, Tsung, K, John, EM, Torres-Mejia, G, Carvajal-Carmona, L, Echeverry, MM, Tuazon, AMD, Ramirez, C, Bohórquez, ME, Prieto, R, Criollo, Á, Ramírez, C, Estrada, AP, Suáres, JJ, Mateus, G, Castro, JM, Sánchez, Y, Murillo, R, Lucia Serrano, M, Sanabria, C, Olaya, JG, Vélez, A, Carmona, JA, Rodríguez, NG, Serón Sousa, C, Mendez, CEA, Galviz, AIO, Gignoux, CR, Eng, C, Gonzalez-Burchard, E, Henderson, B, Marchand, LL, Kooperberg, C, Hou, L, Agalliu, I, Kraft, P, Lindström, S, Perez-Stable, EJ, Haiman, CA & Ziv, E 2014, 'Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25', Nature communications, vol. 5, 5260. https://doi.org/10.1038/ncomms6260

TY - JOUR

T1 - Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25

AU - Fejerman, Laura

AU - Ahmadiyeh, Nasim

AU - Hu, Donglei

AU - Huntsman, Scott

AU - Beckman, Kenneth B.

AU - Caswell, Jennifer L.

AU - Tsung, Karen

AU - John, Esther M.

AU - Torres-Mejia, Gabriela

AU - Carvajal-Carmona, Luis

AU - Echeverry, María Magdalena

AU - Tuazon, Anna Marie D.

AU - Ramirez, Carolina

AU - Bohórquez, Mabel Elena

AU - Prieto, Rodrigo

AU - Criollo, Ángel

AU - Ramírez, Carolina

AU - Estrada, Ana Patricia

AU - Suáres, John Jairo

AU - Mateus, Gilbert

AU - Castro, Jorge Mario

AU - Sánchez, Yesid

AU - Murillo, Raúl

AU - Lucia Serrano, Martha

AU - Sanabria, Carolina

AU - Olaya, Justo Germán

AU - Vélez, Alejandro

AU - Carmona, Jenny Andrea

AU - Rodríguez, Nancy Guerrero

AU - Serón Sousa, Cristina

AU - Mendez, Cesar Eduardo Alvarez

AU - Galviz, Ana Isabel Orduz

AU - Gignoux, Christopher R.

AU - Eng, Celeste

AU - Gonzalez-Burchard, Esteban

AU - Henderson, Brian

AU - Marchand, Loic Le

AU - Kooperberg, Charles

AU - Hou, Lifang

AU - Agalliu, Ilir

AU - Kraft, Peter

AU - Lindström, Sara

AU - Perez-Stable, Eliseo J.

AU - Haiman, Christopher A.

AU - Ziv, Elad

N1 - Funding Information: We want to thank the study participants. This work was supported by the National Cancer Institute (K01 CA160607 to L.F., R01 CA120120 and K24 CA169004 to E.Z. and R01 CA132839 to C.A.H.), the Center for Aging in Diverse Communities (CADC) under the Resource Centers for Minority Aging Research programme by the National Institute on Aging (P30-AG15272) and the National Cancer Institute grant from the Special Population Network programme to the University of Texas, San Antonio (Redes En Acción no. U01CA86117). The San Francisco Bay Area Breast Cancer Study was supported by the National Cancer Institute (CA63446 and CA77305), the US Department of Defense (DAMD17-96-1-6071) and the California Breast Cancer Research Program (7PB-0068). The Northern California Breast Cancer Family Registry was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The Multiethnic Cohort Study was supported by the National Institutes of Health grants R01 CA63464 and R37 CA54281, R01 CA132839, 5UM1CA164973. The GALA1 study was supported by The National Institutes of Health (HL078885, AI077439 and HL088133). The Mexico Breast Cancer Study was funded by Consejo Nacional de Ciencia y Tecnología (SALUD-2002-C01-7462). The COLUMBUS study receives support from GSK Oncology (Ethnic Research Initiative), University of Tolima, University of California Davis and The V Foundation. L.C.-C. is a V Foundation V Scholar. A.M.D.T. is supported by the Howard Hughes Medical Institute, Integrating Medicine into Basic Science fellowship. The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. Genotyping of MEC samples was also supported by the Slim Initiative in Genomic Medicine for the Americas (SIGMA), a joint US–Mexico project funded by the Carlos Slim Health Institute. Publisher Copyright: © 2014 Macmillan Publishers Limited. All rights reserved.

PY - 2014/10/20

Y1 - 2014/10/20

N2 - 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 5′ 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 × 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.

AB - 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 5′ 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 × 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84923773863&partnerID=8YFLogxK

U2 - 10.1038/ncomms6260

DO - 10.1038/ncomms6260

M3 - Article

C2 - 25327703

AN - SCOPUS:84923773863

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 5260

ER -

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

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