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mTOR pathway candidate genes and energy intake interaction on breast cancer risk in Black women from the Women’s Circle of Health Study

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Abstract

Background

Excessive energy intake has been shown to affect the mammalian target of the rapamycin (mTOR) signaling pathway and breast cancer risk. It is not well understood whether there are gene-environment interactions between mTOR pathway genes and energy intake in relation to breast cancer risk.

Methods

The study included 1642 Black women (809 incident breast cancer cases and 833 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 and quartiles of energy intake in relation to breast cancer risk overall and by ER− defined subtypes using Wald test with a 2-way interaction term.

Results

AKT1 rs10138227 (C > T) was only associated with a decreased overall breast cancer risk among women in quartile (Q)2 of energy intake, odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.40, 0.91 (p-interaction = 0.042). Similar results were found in ER− tumors. AKT rs1130214 (C > A) was associated with decreased overall breast cancer risk in Q2 (OR = 0.63, 95% CI 0.44, 0.91) and Q3 (OR = 0.65, 95% CI 0.48, 0.89) (p-interaction = 0.026). HIF-1α C1772T rs11549465 (C > T) was associated with decreased overall breast cancer risk in Q4 (OR = 0.29, 95% CI 0.14, 0.59, p-interaction = 0.007); the results were similar in ER+ tumors. These interactions became non-significant after correction for multiple comparisons.

Conclusion

Our findings suggest that mTOR genetic variants may interact with energy intake in relation to breast cancer risk, including the ER− subtype, in Black women. Future studies should confirm these findings.

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Data availability

Data will be made available on request.

Abbreviations

AKT1:

AKT Serine/Threonine Kinase 1 or Protein Kinase B

BMI:

Body mass index

CI:

Confidence intervals

EGF:

Epidermal growth factor

EIF4E:

Eukaryotic initiation factor 4EER: estrogen receptor

HIF1A:

Hypoxia inducible factor 1 subunit alpha

HIF-1:

Hypoxia-inducible factor-1

IGF-I:

Insulin-like growth factor I

4E-BP1:

Eukaryotic initiation factor 4E-binding protein 1

FFQs:

Food frequency questionnaires

mTOR:

Mammalian target of rapamycin

mTORC1:

MTOR complex 1

mTORC2:

MTOR complex 2

OR:

Odds ratio

PDGF:

Platelet-derived growth factor

PI3K:

Phosphatidylinositol 3-kinase

Q:

Quartile

RPS6KB1:

Ribosomal protein S6 kinase B1

SNPs:

Single-nucleotide polymorphisms

S6K1:

P70 ribosomal S6 kinase 1

TSC2:

Tuberous sclerosis complex 2

WCHS:

Women’s Circle of Health Study

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Funding

This work was supported by grants from the US National Institutes of Health, The National Cancer Institute (grant number P01 CA151135 J.R.P. and C.B.A, R01CA098663 to J.R.P.; R01 CA100598 to C.B.A. and E.V.B; R01 CA185623, P30 CA016056, P30 CA072720, K07 CA201334, R37 CA248371); the Breast Cancer Research Foundation (C.B.A., C–CH).

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Authors and Affiliations

  1. Department of Epidemiology, University of Florida, Gainesville, FL, USA

    Mmadili N. Ilozumba, Lusine Yaghjyan, Jinying Zhao & Ting-Yuan David Cheng

  2. Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA

    Mmadili N. Ilozumba

  3. Department of Biostatistics, University of Florida, Gainesville, FL, USA

    Susmita Datta

  4. Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Chi-Chen Hong, Song Yao, Christine B. Ambrosone & Ting-Yuan David Cheng

  5. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    Kathryn L. Lunetta

  6. Slone Epidemiology Center, Boston University, Boston, MA, USA

    Gary Zirpoli & Julie R. Palmer

  7. Cancer Epidemiology and Health Outcomes, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Elisa V. Bandera

  8. 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 David Cheng

Authors
  1. Mmadili N. Ilozumba
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  2. Lusine Yaghjyan
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  3. Susmita Datta
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  4. Jinying Zhao
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  5. Chi-Chen Hong
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  6. Kathryn L. Lunetta
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  10. Song Yao
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  11. Christine B. Ambrosone
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  12. Ting-Yuan David Cheng
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Contributions

Study conception and design: MNI, TYC. Data acquisition: JZ, JRP, SY, CCH, EVB, CBA. Writing—initial draft: MNI. Data analysis: MNI. Data interpretation: MNI, TYC, LY. Contributed to the statistical methods: KLL, TYC, LY, SD, JZ. Revised the paper: MNI, TYC, LY, SD, JZ, GZ, SY, EB. Writing—final review and approval: all authors. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mmadili N. Ilozumba or Ting-Yuan David Cheng.

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Ilozumba, M.N., Yaghjyan, L., Datta, S. et al. mTOR pathway candidate genes and energy intake interaction on breast cancer risk in Black women from the Women’s Circle of Health Study. Eur J Nutr 62, 2593–2604 (2023). https://doi.org/10.1007/s00394-023-03176-y

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