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- Title
mTOR pathway candidate genes and energy intake interaction on breast cancer risk in Black women from the Women's Circle of Health Study.
- Authors
Ilozumba, Mmadili N.; Yaghjyan, Lusine; Datta, Susmita; Zhao, Jinying; Hong, Chi-Chen; Lunetta, Kathryn L.; Zirpoli, Gary; Bandera, Elisa V.; Palmer, Julie R.; Yao, Song; Ambrosone, Christine B.; Cheng, Ting-Yuan David
- 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.
- Subjects
NEW Jersey; NEW York (State); BREAST tumor prevention; BREAST tumor risk factors; PROTEIN kinases; CONFIDENCE intervals; FOOD consumption; SINGLE nucleotide polymorphisms; ONCOGENES; CASE-control method; SIGNAL peptides; CELLULAR signal transduction; RISK assessment; CANCER patients; TUMOR suppressor genes; DESCRIPTIVE statistics; RESEARCH funding; ODDS ratio; AFRICAN Americans; HORMONE receptor positive breast cancer; DISEASE risk factors
- Publication
European Journal of Nutrition, 2023, Vol 62, Issue 6, p2593
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-023-03176-y