PO.PS01.01 · 人群科学
27-羟基胆固醇代谢酶的表达与乳腺癌临床病理特征：多种族队列研究
Expression of 27-hydroxycholesterol metabolizing enzymes and breast cancer clinicopathological characteristics: The Multiethnic Cohort Study
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摘要 Abstract
中文摘要
背景：肥胖是绝经后乳腺癌预后的主要可改变风险因素。肥胖与绝经后乳腺癌之间关联的机制包括较高水平的雌二醇、胆固醇和炎症。循环胆固醇通过甾醇27-羟化酶（CYP27A1）代谢为27-羟基胆固醇（27HC）。27HC由氧化甾醇7α-羟化酶（CYP7B1）分解代谢。27HC可通过在乳腺肿瘤中作为内源性选择性雌激素受体调节剂发挥功能来调控乳腺癌的病理生物学。在本研究中，我们在一个多种族人群中考察了肿瘤组织中CYP27A1和CYP7B1表达水平与乳腺癌临床病理特征之间的关联。
方法：使用来自多种族队列研究中510名绝经后女性（62名非裔美国人、114名日裔美国人、93名拉丁裔、135名夏威夷原住民和106名白人）的浸润性乳腺肿瘤组织，采用NanoString nCounter Breast Cancer 360™（BC360）panel（包括51个额外的自定义基因）进行靶向基因表达谱分析。采用广义有序logistic回归分析考察CYP27A1和CYP7B1基因表达水平与临床病理特征——分期、PAM50分子亚型（Luminal A、B、HER2富集型、基底样型）和NanoString复发风险（ROR）评分之间的关联。
结果：CYP27A1表达与诊断时晚期相较局限期的较低可能性相关（OR=0.87；95% CI 0.74, 1.02）。未观察到CYP7B1与分期的关联。与Luminal A亚型相比，CYP27A1表达与HER2富集型（OR=0.71；95% CI 0.55, 0.92）和Luminal B（OR=0.71；95% CI 0.58, 0.89）亚型的较低可能性相关。与Luminal A相比，CYP7B1表达与基底样型（OR=1.23；95% CI 1.02, 1.49）、HER2富集型（OR=0.59；95% CI 0.43, 0.80）和Luminal B（OR=0.43；95% CI 0.32, 0.58）亚型相关。未观察到CYP27A1与ROR类别（低、中、高）的显著关联。相比之下，CYP7B1表达与较低的复发风险评分相关（ROR中 vs. 低：OR=0.77；95% CI 0.62, 0.96；ROR高 vs. 低：OR=0.56；95% CI 0.40, 0.79）。
结论：本研究发现，在一个多种族女性人群中，乳腺肿瘤中27HC代谢酶CYP27A1和CYP7B1的基因表达水平与分期、乳腺癌亚型和复发风险相关。
查看英文原文 English abstract
Background: Obesity is a major modifiable risk factor for postmenopausal breast cancer prognosis. Mechanisms underlying the association between obesity and post-menopausal breast cancer include higher levels of estradiol, cholesterol, and inflammation. Circulating cholesterol is metabolized into 27-hydroxychlolesterol (27HC) by the sterol 27-hydroxylase enzyme (CYP27A1). 27HC is catabolized by the oxysterol 7alpha-hydroxylase enzyme (CYP7B1). 27HC can regulate breast cancer pathobiology by functioning as an endogenous selective estrogen receptor modulator in breast tumors. In this study, we examined the associations of expression levels of CYP27A1 and CYP7B1 in tumor tissue with clinicopathological characteristics of breast cancer in a multiethnic population.
Methods: Invasive breast tumor tissue from 510 postmenopausal females (62 African American, 114 Japanese American, 93 Latino, 135 Native Hawaiian, and 106 White) in the Multiethnic Cohort Study were used for targeted profiling of gene expression using the NanoString nCounter Breast Cancer 360™ (BC360) Panel, including 51 additional custom genes. Generalized odds logistic regression analysis was conducted to examine associations of gene expression levels for CYP27A1 and CYP7B1 with clinicopathological characteristics -- stage, PAM50 molecular subtype (Luminal A, B, HER2-enriched, Basal-like) and NanoString Risk of Recurrence (ROR) score.
Results: CYP27A1 expression was associated with a lower likelihood of advanced versus localized stage at diagnosis (OR=0.87; 95% CI 0.74, 1.02). No association was observed for CYP7B1 with stage. CYP27A1 expression was associated with a lower likelihood of HER2-enciched (OR=0.71; 95% CI 0.55, 0.92) and Luminal B (OR=0.71; 95% CI 0.58, 0.89) subtypes in comparison to Luminal A subtypes. CYP7B1 expression was associated with Basal-like (OR=1.23; 95% CI 1.02, 1.49), HER2-enriched (OR=0.59; 95% CI 0.43, 0.80), and Luminal B (OR=0.43; 95% CI 0.32, 0.58) subtypes in comparison to Luminal A. No significant association was observed for CYP27A1 and ROR categories (low, intermediate, and high). In contrast, CYP7B1 expression was associated with lower risk of recurrence score (ROR intermediate vs. low: OR=0.77; 95% CI 0.62, 0.96; ROR high vs. low: OR=0.56; 95% CI 0.40, 0.79).
Conclusion: This study identified that gene expression levels of 27HC metabolizing enzymes, CYP27A1 and CYP7B1, in breast tumors were associated stage, breast cancer subtype, and risk of recurrence among a multiethnic population of women.
利益披露 Disclosure
L. W. Loo, None..
Y. Li, None..
K. K. White, None..
J. A. Aparicio, None..
B. Y. Hernandez, None..
A. H. Wu, None..
C. Haiman, None..
L. Le Marchand, None..
L. R. Wilkens, None..
I. Cheng, None.