PMID- 28582508
OWN - NLM
STAT- MEDLINE
DCOM- 20171005
LR  - 20221207
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 38
IP  - 8
DP  - 2017 Aug 1
TI  - Association of breast cancer risk and the mTOR pathway in women of African 
      ancestry in 'The Root' Consortium.
PG  - 789-796
LID - 10.1093/carcin/bgx055 [doi]
AB  - 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.
CI  - (c) The Author 2017. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Wang, Shengfeng
AU  - Wang S
AD  - Department of Medicine, Center for Clinical Cancer Genetics and Global Health, 
      University of Chicago, Chicago, IL, USA.
FAU - Huo, Dezheng
AU  - Huo D
AD  - Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
FAU - Ogundiran, Temidayo O
AU  - Ogundiran TO
AD  - Department of Surgery, College of Medicine, University of Ibadan, Ibadan, 
      Nigeria.
FAU - Ojengbede, Oladosu
AU  - Ojengbede O
AD  - Center for Population and Reproductive Health, College of Medicine, University of 
      Ibadan, Ibadan, Nigeria.
FAU - Zheng, Wei
AU  - Zheng W
AD  - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, 
      Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
FAU - Nathanson, Katherine L
AU  - Nathanson KL
AD  - Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Nemesure, Barbara
AU  - Nemesure B
AD  - Department of Preventive Medicine, State University of New York at Stony Brook, 
      Stony Brook, NY, USA.
FAU - Ambs, Stefan
AU  - Ambs S
AD  - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
FAU - Olopade, Olufunmilayo I
AU  - Olopade OI
AD  - To whom correspondence should be addressed. Tel: +1 773 702 1632; Fax: +1 773 834 
      1659; Email: folopade@bsd.uchicago.edu
FAU - Zheng, Yonglan
AU  - Zheng Y
AUID- ORCID: 0000-0001-9397-0409
AD  - To whom correspondence should be addressed. Tel: +1 773 702 1632; Fax: +1 773 834 
      1659; Email: folopade@bsd.uchicago.edu
LA  - eng
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (PRKAG3 protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 90kDa, polypeptide 3)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*genetics
MH  - Alleles
MH  - Black People/genetics
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinogenesis/genetics/pathology
MH  - Estrogen Receptor alpha/genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - Ribosomal Protein S6 Kinases, 90-kDa/*genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*genetics
PMC - PMC5862308
EDAT- 2017/06/06 06:00
MHDA- 2017/10/06 06:00
PMCR- 2018/08/01
CRDT- 2017/06/06 06:00
PHST- 2017/03/20 00:00 [received]
PHST- 2017/06/02 00:00 [accepted]
PHST- 2017/06/06 06:00 [pubmed]
PHST- 2017/10/06 06:00 [medline]
PHST- 2017/06/06 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - 3861479 [pii]
AID - bgx055 [pii]
AID - 10.1093/carcin/bgx055 [doi]
PST - ppublish
SO  - Carcinogenesis. 2017 Aug 1;38(8):789-796. doi: 10.1093/carcin/bgx055.