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

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms6260

2041-1723

Laura Fejerman, Nasim Ahmadiyeh, Donglei Hu, Scott Huntsman, Kenneth B. Beckman, Jennifer L. Caswell‐Jin, Karen Tsung, Esther M. John, Gabriela Torres-Mejı́a, Luis G. Carvajal‐Carmona, María Magdalena Echeverry, Anna Marie Tuazon, Carolina Ramírez‐Santana, Luis G. Carvajal‐Carmona, María Magdalena Echeverry, Mábel Bohórquez, Rodrigo Prieto, Ángel Criollo, Carolina Ramírez‐Santana, Ana P. Estrada-Florez, John Jairo Suáres, Gilbert Mateus, Jorge Mario Castro, Yesid Sánchez, Raúl Murillo, Martha Lucía Serrano, Carolina Sanabria, Justo Germán Olaya, Fernando Bolaños, Alejandro Vélez, Jenny Andrea Carmona, Alejandro Vélez, Nancy Rodriguez, Cristina Serón Sousa, Cesar Eduardo Alvarez Mendez, Ana Isabel Orduz Galviz, Christopher R. Gignoux, Celeste Eng, Esteban González-Burchard, Brian E. Henderson, Loı̈c Le Marchand, Charles Kooperberg, Lifang Hou, Ilir Agalliu, Peter Kraft, Sara Lindström, Eliseo J. Pérez‐Stable, Christopher A. Haiman, Elad Ziv,

Cancer Risks and Factors

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.