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Carcinogenesis. 2017 Aug 1;38(8):789-796. doi: 10.1093/carcin/bgx055.

Association of breast cancer risk and the mTOR pathway in women of African ancestry in 'The Root' Consortium.

Author information

1
Department of Medicine, Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, IL, USA.
2
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
3
Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
4
Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
5
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
6
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
7
Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
8
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
9
To whom correspondence should be addressed. Tel: +1 773 702 1632; Fax: +1 773 834 1659; Email: folopade@bsd.uchicago.edu

Abstract

Functional studies have elucidated the role of the mammalian target of rapamycin (mTOR) pathway in breast carcinogenesis, but to date, there is a paucity of data on its contribution to breast cancer risk in women of African ancestry. We examined 47628 SNPs in 61 mTOR pathway genes in the genome wide association study of breast cancer in the African Diaspora study (The Root consortium), which included 3686 participants (1657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product (ARTP) test for 10994 SNPs that were not highly correlated (r2 < 0.8). Odds ratio (OR) and 95% confidence interval (CI) were estimated with logistic regression for each single-nucleotide polymorphism. The mTOR pathway was significantly associated with overall and estrogen receptor-negative (ER-) breast cancer risk (P = 0.003 and 0.03, respectively). PRKAG3 (Padj = 0.0018) and RPS6KA3 (Padj = 0.061) were the leading genes for the associations with overall breast cancer risk and ER- breast cancer risk, respectively. rs190843378 in PRKAG3 was statistically significant after gene-level adjustment for multiple comparisons (OR = 0.50 for each T allele, 95% CI = 0.38-0.66, Padj = 3.6E-05), with a statistical power of 0.914. These results provide new insights on the biological relevance of the mTOR pathway in breast cancer progression and underscore the need for more genetic epidemiology studies of breast cancer in the African Diaspora.

PMID:
28582508
PMCID:
PMC5862308
DOI:
10.1093/carcin/bgx055
[Indexed for MEDLINE]
Free PMC Article

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