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mTOR pathway candidate genes and physical activity interaction on breast cancer risk in black women from the women’s circle of health study

  • Epidemiology
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Abstract

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.

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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); and the Breast Cancer Research Foundation (C.B.A., C–CH).

Author information

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

    Zhihong Gong, 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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  4. Jinying Zhao
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  5. Zhihong Gong
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  6. Chi-Chen Hong
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  11. Song Yao
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  12. Christine B. Ambrosone
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  13. Ting-Yuan David Cheng
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Contributions

MNI and TYC contributed to study conception and design. ZG, JRP, SY, CCH, EVB, and CBA contributed to data acquisition. MNI contributed to writing of the initial draft. MNI contributed to data analysis. MNI, TYC, and LY contributed to data interpretation. KLL, TYC, LY, SD, and JZ contributed to the statistical methods. MNI, TYC, LY, SD, JZ, ZG, GZ, SY, and EB revised the paper. Writing—final review and approval were performed by 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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The authors declare that they have no conflict of interest.

Ethical approval

The WCHS protocol was approved by the Institutional Review Boards at Roswell Park Cancer Institute, the Rutgers Cancer Institute of New Jersey, Mount Sinai School of Medicine, and participating hospitals in New York. The current study was approved by the University of Florida’s institutional review board.

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Signed informed consent was obtained from all individual participants included in the study.

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Ilozumba, M.N., Yaghjyan, L., Datta, S. et al. mTOR pathway candidate genes and physical activity interaction on breast cancer risk in black women from the women’s circle of health study. Breast Cancer Res Treat 199, 137–146 (2023). https://doi.org/10.1007/s10549-023-06902-6

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