Department of Epidemiology, University of Florida, Gainesville, FL, USA.
Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Eur J Nutr. 2023 Sep;62(6):2593-2604. doi: 10.1007/s00394-023-03176-y. Epub 2023 May 20.
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.
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.
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.
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.
已有研究表明，能量摄入过多会影响哺乳动物雷帕霉素靶蛋白（mTOR）信号通路并增加乳腺癌风险。但是，目前尚不清楚 mTOR 通路基因与能量摄入之间是否存在基因-环境相互作用，以及这种相互作用与乳腺癌风险之间的关系。
本研究纳入了来自女性健康研究圈（WCHS）的 1642 名黑人女性（809 例乳腺癌新发病例和 833 例对照）。我们通过 Wald 检验和双向交互项，分析了 20 个 mTOR 通路基因中的 43 个候选单核苷酸多态性（SNP）与能量摄入四分位的交互作用与乳腺癌总体发病风险及雌激素受体（ER）定义的亚型发病风险之间的关系。
AKT1 rs10138227（C>T）仅与能量摄入四分位（Q）2 的女性乳腺癌总体发病风险降低相关，比值比（OR）为 0.60，95%置信区间（CI）为 0.40-0.91（p 交互 = 0.042）。在 ER+肿瘤中也观察到了类似的结果。AKT rs1130214（C>A）与能量摄入 Q2（OR = 0.63，95% CI 0.44-0.91）和 Q3（OR = 0.65，95% CI 0.48-0.89）的乳腺癌总体发病风险降低相关（p 交互 = 0.026）。HIF-1α C1772T rs11549465（C>T）与能量摄入 Q4 的乳腺癌总体发病风险降低相关（OR = 0.29，95% CI 0.14-0.59，p 交互 = 0.007）；在 ER+肿瘤中也观察到了类似的结果。这些交互作用在经过多重比较校正后变得无统计学意义。
本研究结果提示，mTOR 基因变异可能与能量摄入相互作用，进而影响黑人女性的乳腺癌发病风险，包括 ER- 型乳腺癌。未来的研究应进一步证实这些结果。
