Prospective Analysis of Circulating Biomarkers and Ovarian Cancer Risk in the UK Biobank.

IF 3.7 3区医学 Q2 ONCOLOGY

Cancer Epidemiology Biomarkers & Prevention Pub Date : 2024-10-02 DOI:10.1158/1055-9965.EPI-24-0319

Naoko Sasamoto, Cassandra A Hathaway, Mary K Townsend, Kathryn L Terry, Britton Trabert, Shelley S Tworoger

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引用次数: 0

Abstract

Background: Risk factors have a limited ability to predict individuals at high risk of developing ovarian cancer among average-risk women, highlighting the need for discovery of novel biomarkers. In the UK Biobank, we investigated serum biomarkers commonly measured in clinical laboratory tests and ovarian cancer risk.

Methods: We conducted a prospective analysis of 20 serum biomarkers and ovarian cancer risk in 232,037 female UK Biobank participants (including 1,122 incident ovarian cancer cases diagnosed from 2006 to 2020). Multivariable adjusted Cox proportional hazards models were used to examine associations between biomarkers and ovarian cancer risk overall and by histotype. FDR was used to account for multiple testing.

Results: Overall, higher levels of insulin-like growth factor (IGF)-1 [RRquartile 4 vs. 1 = 0.73; 95% confidence interval (CI), 0.60-0.87; P-trend = 0.002/FDR = 0.04], HbA1c (RRquartile 4 vs. 1 = 0.74; 95% CI, 0.62-0.89; P-trend = 0.002/FDR = 0.04), and alanine aminotransferase (RRquartile 4 vs. 1 = 0.76; 95% CI, 0.63-0.91; P-trend = 0.002/FDR = 0.04) were significantly associated with lower ovarian cancer risk. When stratified by histotype, higher IGF1 levels were associated with lower risk of serous (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.58-0.91; P-trend = 0.01/FDR = 0.20) and clear cell tumors (RRquartile 4 vs. 1 = 0.18; 95% CI, 0.07-0.49; P-trend = 0.001/FDR = 0.02), and higher HbA1c levels were associated with lower risk of serous tumors (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.59-0.90; P-trend = 0.004/FDR = 0.08).

Conclusions: We observed that higher levels of circulating IGF1, HbA1c, and alanine aminotransferase were associated with lower ovarian cancer risk.

Impact: These results suggest metabolism of glucose/amino acid and insulin/IGF1 signaling pathway may be contributing to ovarian carcinogenesis. Further research is needed to replicate our findings and elucidate how systemic changes in metabolism impact ovarian carcinogenesis.

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英国生物库中循环生物标志物与卵巢癌风险的前瞻性分析。

背景：在普通风险女性中，风险因素预测卵巢癌高风险个体的能力有限，这凸显了发现新型生物标志物的必要性。在英国生物库中，我们调查了临床实验室检测中常用的血清生物标志物和卵巢癌风险：我们对 232,037 名英国生物库女性参与者（包括 2006-2020 年间诊断出的 1,122 例卵巢癌病例）的 20 种血清生物标志物和卵巢癌风险进行了前瞻性分析。多变量调整考克斯比例危险模型用于研究生物标志物与总体卵巢癌风险和不同组织类型卵巢癌风险之间的关系。假发现率用于考虑多重检验：总体而言，IGF-1（RRquartile 4 vs. 1=0.73，95%CI=0.60-0.87；p-trend=0.002/FDR=0.04）、HbA1c（RRquartile 4 vs. 1=0.74，95%CI=0.62-0.89；p-trend=0.002/FDR=0.04）和丙氨酸氨基转移酶（RRquartile 4 vs. 1=0.76，95%CI=0.63-0.91；p-trend=0.002/FDR=0.04）与较低的卵巢癌风险显著相关。按组织类型分层时，较高的IGF-1水平与较低的浆液性肿瘤（RR四分位数4 vs. 1=0.73，95%CI=0.58-0.91；p-趋势=0.01/FDR=0.20）和透明细胞肿瘤（RR四分位数4 vs. 1=0.18，95%CI=0.58-0.91；p-趋势=0.01/FDR=0.04）风险相关。1=0.18，95%CI=0.07-0.49；p-trend=0.001/FDR=0.02），HbA1c水平越高，患浆液性肿瘤的风险越低（RRquartile 4 vs. 1=0.73，95%CI=0.59-0.90；p-trend=0.004/FDR=0.08）：我们观察到，较高水平的循环 IGF-1、HbA1c 和丙氨酸氨基转移酶与较低的卵巢癌风险相关：这些结果表明，葡萄糖/氨基酸代谢和胰岛素/IGF-1 信号通路可能会导致卵巢癌的发生。我们需要进一步研究，以复制我们的发现，并阐明新陈代谢的系统性变化如何影响卵巢癌的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Epidemiology Biomarkers & Prevention 医学-公共卫生、环境卫生与职业卫生

CiteScore

6.50

自引率

2.60%

发文量

538

审稿时长

1.6 months

期刊介绍： Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.