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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

Year: 2016
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1038/npjbcancer.2016.34
Authors: Edward A Ruiz-Narváez, Kathryn L Lunetta, Chi-Chen Hong, Stephen Haddad, Song Yao, Ting-Yuan David Cheng, Jeannette T Bensen, Elisa V Bandera, Christopher A Haiman, Melissa A Troester, Christine B Ambrosone, Lynn Rosenberg, Julie R Palmer
Institutions: Boston University, Roswell Park Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Rutgers, The State University of New Jersey, Rutgers Cancer Institute, USC Norris Comprehensive Cancer Center
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,790
Awards: Uncoupling obesity from breast cancer in African American women, G1569999668, G1660206989, A GENOME-WIDE BREAST CANCER SCAN IN AFRICAN AMERICANS, G2069482854, G2313542652, G2344417776, mTOR pathway in breast cancer subtypes by race: A molecular pathological study, G299563851, G3465312822, G4119534169, G4592503987, G4907478063, G5824370075, G5850682332, G7011691652, Epidemiology of Breast Cancer Subtypes in African American Women: a Consortium, A Follow-up Study for Causes of Cancer in Black Women, G7697152668, G8820111440, G9000007592, G9000021152, G9000043966, G9000051068, G9000061634, G9000062283, G9000073604, G9000083102, G9000084571, G9000118332, G9000147011, G9000168100, G9000173417, G9000176900, G9000179783, G9000182874, G9000207854, G9000216949, G9000233422, G9000266857, G9000355445, Cancer Center Support Grant
OpenAlex ID: W2533099547
FWCI: 1.444
Cites: 57
Cited by: 11
Related to: 10