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

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.

• Authors: Mmadili N Ilozumba, Lusine Yaghjyan, Susmita Datta, Jinying Zhao, Zhihong Gong, Chi-Chen Hong, Kathryn L Lunetta, Gary Zirpoli, Elisa V Bandera, Julie R Palmer, Song Yao, Christine B Ambrosone, Ting-Yuan David Cheng
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 199 Issue 1 Pg. 137-146 (May 2023) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 36882608 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• MTOR protein, human
• Receptors, Estrogen
• TOR Serine-Threonine Kinases
• EIF4E protein, human
• AKT1 protein, human

Topics

• Female
• Humans
• Black or African American
• Breast Neoplasms (etiology, genetics)
• Case-Control Studies
• Exercise
• Genetic Association Studies
• Genetic Predisposition to Disease
• Polymorphism, Single Nucleotide
• Receptors, Estrogen (genetics, metabolism)
• Risk Factors
• TOR Serine-Threonine Kinases (genetics)