Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium

The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin...

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Main Authors:	Ruiz-Narváez, Edward A, Lunetta, Kathryn L, Hong, Chi-Chen, Haddad, Stephen, Yao, Song, Cheng, Ting-Yuan David, Bensen, Jeannette T, Bandera, Elisa V, Haiman, Christopher A, Troester, Melissa A, Ambrosone, Christine B, Rosenberg, Lynn, Palmer, Julie R
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142758/

id	pubmed-5142758
recordtype	oai_dc
spelling	pubmed-51427582016-12-07 Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium Ruiz-Narváez, Edward A Lunetta, Kathryn L Hong, Chi-Chen Haddad, Stephen Yao, Song Cheng, Ting-Yuan David Bensen, Jeannette T Bandera, Elisa V Haiman, Christopher A Troester, Melissa A Ambrosone, Christine B Rosenberg, Lynn Palmer, Julie R Article The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin/IGF, growth hormone, and leptin pathways to identify genetic variation associated with risk of breast cancer overall, and for estrogen receptor (ER) subtypes. Tag single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina SNP array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs genotyped or imputed in 3,663 breast cancer cases, (1,983 ER-positive and 1,098 ER-negative) and 4,687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African-American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint test to determine the association of each gene with overall breast cancer and ER subtypes. The most significant gene associations (P⩽0.01) were BAIAP2 and CALM2 for overall breast cancer; BAIAP2 and CSNK2A1 for ER+ breast cancer; and BRAF, BAD, and MAPK3 for ER− breast cancer. The association of BAD with ER− breast cancer was explained by a two-SNP risk model; all other associations were best explained by one-SNP risk models. In total, six genes and seven SNPs had suggestive associations with overall breast cancer or ER subtypes in African-American women. Nature Publishing Group 2016-10-26 /pmc/articles/PMC5142758/ /pubmed/27942580 http://dx.doi.org/10.1038/npjbcancer.2016.34 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ruiz-Narváez, Edward A Lunetta, Kathryn L Hong, Chi-Chen Haddad, Stephen Yao, Song Cheng, Ting-Yuan David Bensen, Jeannette T Bandera, Elisa V Haiman, Christopher A Troester, Melissa A Ambrosone, Christine B Rosenberg, Lynn Palmer, Julie R
spellingShingle	Ruiz-Narváez, Edward A Lunetta, Kathryn L Hong, Chi-Chen Haddad, Stephen Yao, Song Cheng, Ting-Yuan David Bensen, Jeannette T Bandera, Elisa V Haiman, Christopher A Troester, Melissa A Ambrosone, Christine B Rosenberg, Lynn Palmer, Julie R Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
author_facet	Ruiz-Narváez, Edward A Lunetta, Kathryn L Hong, Chi-Chen Haddad, Stephen Yao, Song Cheng, Ting-Yuan David Bensen, Jeannette T Bandera, Elisa V Haiman, Christopher A Troester, Melissa A Ambrosone, Christine B Rosenberg, Lynn Palmer, Julie R
author_sort	Ruiz-Narváez, Edward A
title	Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
title_short	Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
title_full	Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
title_fullStr	Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
title_full_unstemmed	Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
title_sort	genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in african-american women: the amber consortium
description	The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin/IGF, growth hormone, and leptin pathways to identify genetic variation associated with risk of breast cancer overall, and for estrogen receptor (ER) subtypes. Tag single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina SNP array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs genotyped or imputed in 3,663 breast cancer cases, (1,983 ER-positive and 1,098 ER-negative) and 4,687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African-American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint test to determine the association of each gene with overall breast cancer and ER subtypes. The most significant gene associations (P⩽0.01) were BAIAP2 and CALM2 for overall breast cancer; BAIAP2 and CSNK2A1 for ER+ breast cancer; and BRAF, BAD, and MAPK3 for ER− breast cancer. The association of BAD with ER− breast cancer was explained by a two-SNP risk model; all other associations were best explained by one-SNP risk models. In total, six genes and seven SNPs had suggestive associations with overall breast cancer or ER subtypes in African-American women.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142758/
_version_	1613763590582435840

Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium

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