PMID- 36882608
OWN - NLM
STAT- MEDLINE
DCOM- 20230510
LR  - 20240502
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 199
IP  - 1
DP  - 2023 May
TI  - mTOR pathway candidate genes and physical activity interaction on breast cancer 
      risk in black women from the women's circle of health study.
PG  - 137-146
LID - 10.1007/s10549-023-06902-6 [doi]
AB  - BACKGROUND: Physical activity has been shown to affect the mammalian target of 
      rapamycin (mTOR) signaling pathway and consequently breast carcinogenesis. Given 
      that Black women in the USA are less physically active, it is not well understood 
      whether there are gene-environment interactions between mTOR pathway genes and 
      physical activity in relation to breast cancer risk in Black women. METHODS: The 
      study included 1398 Black women (567 incident breast cancer cases and 831 
      controls) from the Women's Circle of Health Study (WCHS). We examined 
      interactions between 43 candidate single-nucleotide polymorphisms (SNPs) in 20 
      mTOR pathway genes with levels of vigorous physical activity in relation to 
      breast cancer risk overall and by ER-defined subtypes using Wald test with 2-way 
      interaction term and multivariable logistic regression. RESULTS: AKT1 rs10138227 
      (C > T) and AKT1 rs1130214 (C > A) were only associated with a decreased risk of 
      ER + breast cancer among women with vigorous physical activity (odds ratio 
      [OR] = 0.15, 95% confidence interval (CI) 0.04, 0.56, for each copy of the T 
      allele, p-interaction = 0.007 and OR = 0.51, 95% CI 0.27, 0.96, for each copy of 
      the A allele, p-interaction = 0.045, respectively). MTOR rs2295080 (G > T) was 
      only associated with an increased risk of ER + breast cancer among women with 
      vigorous physical activity (OR = 2.24, 95% CI 1.16, 4.34, for each copy of the G 
      allele; p-interaction = 0.043). EIF4E rs141689493 (G > A) was only associated 
      with an increased risk of ER- breast cancer among women with vigorous physical 
      activity (OR = 20.54, 95% CI 2.29, 184.17, for each copy of the A allele; 
      p-interaction = 0.003). These interactions became non-significant after 
      correction for multiple testing (FDR-adjusted p-value > 0.05). CONCLUSION: Our 
      findings suggest that mTOR genetic variants may interact with physical activity 
      in relation to breast cancer risk in Black women. Future studies should confirm 
      these findings.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Ilozumba, Mmadili N
AU  - Ilozumba MN
AUID- ORCID: 0000-0002-9928-3711
AD  - Department of Epidemiology, University of Florida, Gainesville, FL, USA. 
      Mmadili.Ilozumba@hci.utah.edu.
AD  - Department of Population Health Sciences, Huntsman Cancer Institute, University 
      of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA. 
      Mmadili.Ilozumba@hci.utah.edu.
FAU - Yaghjyan, Lusine
AU  - Yaghjyan L
AD  - Department of Epidemiology, University of Florida, Gainesville, FL, USA.
FAU - Datta, Susmita
AU  - Datta S
AD  - Department of Biostatistics, University of Florida, Gainesville, FL, USA.
FAU - Zhao, Jinying
AU  - Zhao J
AD  - Department of Epidemiology, University of Florida, Gainesville, FL, USA.
FAU - Gong, Zhihong
AU  - Gong Z
AD  - Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Hong, Chi-Chen
AU  - Hong CC
AD  - Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Lunetta, Kathryn L
AU  - Lunetta KL
AD  - Department of Biostatistics, Boston University School of Public Health, Boston, 
      MA, USA.
FAU - Zirpoli, Gary
AU  - Zirpoli G
AD  - Slone Epidemiology Center, Boston University, Boston, MA, USA.
FAU - Bandera, Elisa V
AU  - Bandera EV
AD  - Cancer Epidemiology and Health Outcomes, Rutgers Cancer Institute of New Jersey, 
      New Brunswick, NJ, USA.
FAU - Palmer, Julie R
AU  - Palmer JR
AD  - Slone Epidemiology Center, Boston University, Boston, MA, USA.
FAU - Yao, Song
AU  - Yao S
AD  - Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Ambrosone, Christine B
AU  - Ambrosone CB
AD  - Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Cheng, Ting-Yuan David
AU  - Cheng TD
AD  - Department of Epidemiology, University of Florida, Gainesville, FL, USA. 
      ting-yuan.cheng@osumc.edu.
AD  - Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA. ting-yuan.cheng@osumc.edu.
AD  - Division of Cancer Prevention and Control, Department of Internal Medicine, The 
      Ohio State University, Suite 525, 1590 North High Street, Columbus, OH, 43201, 
      USA. ting-yuan.cheng@osumc.edu.
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
GR  - P01 CA151135/CA/NCI NIH HHS/United States
GR  - R37 CA248371/CA/NCI NIH HHS/United States
GR  - R01 CA185623/CA/NCI NIH HHS/United States
GR  - R01 CA100598/CA/NCI NIH HHS/United States
GR  - R01 CA098663/CA/NCI NIH HHS/United States
GR  - K07 CA201334/CA/NCI NIH HHS/United States
GR  - P30 CA072720/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20230308
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (EIF4E protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
SB  - IM
MH  - Female
MH  - Humans
MH  - Black or African American
MH  - *Breast Neoplasms/etiology/genetics
MH  - Case-Control Studies
MH  - Exercise
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, Estrogen/genetics/metabolism
MH  - Risk Factors
MH  - TOR Serine-Threonine Kinases/genetics
PMC - PMC10695183
MID - NIHMS1944147
OTO - NOTNLM
OT  - Black women
OT  - Breast cancer
OT  - Effect modification
OT  - Physical activity
OT  - mTOR pathway
COIS- Conflict of Interest The authors declare that they have no conflict of interest
EDAT- 2023/03/08 06:00
MHDA- 2023/05/01 06:42
PMCR- 2024/05/01
CRDT- 2023/03/07 23:26
PHST- 2023/01/06 00:00 [received]
PHST- 2023/02/17 00:00 [accepted]
PHST- 2023/05/01 06:42 [medline]
PHST- 2023/03/08 06:00 [pubmed]
PHST- 2023/03/07 23:26 [entrez]
PHST- 2024/05/01 00:00 [pmc-release]
AID - 10.1007/s10549-023-06902-6 [pii]
AID - 10.1007/s10549-023-06902-6 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2023 May;199(1):137-146. doi: 
      10.1007/s10549-023-06902-6. Epub 2023 Mar 8.