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

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Resumen

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.

Idioma original	Inglés
Número de artículo	5260
Publicación	Nature Communications
Volumen	5
DOI	https://doi.org/10.1038/ncomms6260
Estado	Publicada - 20 oct. 2014
Publicado de forma externa	Sí

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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, Artículo 5260. https://doi.org/10.1038/ncomms6260

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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",

year = "2014",

month = oct,

day = "20",

doi = "10.1038/ncomms6260",

language = "Ingl{\'e}s",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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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

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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U2 - 10.1038/ncomms6260

DO - 10.1038/ncomms6260

M3 - Artículo en revista científica indexada

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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