Rachel Moon, J Bernadette Moore, Mark A Hull, Michael A Zulyniak
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引用次数: 0
摘要
背景:花生四烯酸(ARA)与结直肠癌(CRC)有关,这是一个重大的公共卫生问题。然而,目前还不确定 ARA 是否会导致结直肠息肉的发生,而结直肠息肉是 CRC 的恶性前体:该研究旨在调查终生暴露于高浓度 ARA 与结直肠息肉发病率之间的关系:来自欧洲、新加坡和中国队列(n = 10,171)的汇总级 GWAS 数据确定了 4 个与血液中 ARA 水平相关的单核苷酸多态性(SNPs)(p < 5 × 10-8)。经过剪枝后,保留了 1 个 SNP(rs174547;p = 3.0 × 10-971)进行两阶段孟德尔随机化:在英国生物数据库(1,391 例;总计 462,933 例)中未观察到 ARA 与结直肠息肉发病率之间的关联(OR = 1.00;95% CI:0.99,1.00;p 值 = 0.50):结论:在一般健康人群中,血液中的 ARA 水平与结直肠息肉发病率无关。这项工作虽然没有提供直接证据,但支持了以下论点:在早期结直肠癌发生过程中,息肉形成的关键因素是 PGE2 等下游脂质介质,而不是 ARA 本身。
Investigation of the Association between High Arachidonic Acid Synthesis and Colorectal Polyp Incidence within a Generally Healthy UK Population: A Mendelian Randomization Approach.
Background: Arachidonic acid (ARA) is associated with colorectal cancer (CRC), a major public health concern. However, it is uncertain if ARA contributes to the development of colorectal polyps which are pre-malignant precursors of CRC.
Objective: The study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence.
Methods: Summary-level GWAS data from European, Singaporean, and Chinese cohorts (n = 10,171) identified 4 single-nucleotide polymorphisms (SNPs) associated with blood ARA levels (p < 5 × 10-8). After pruning, 1 SNP was retained (rs174547; p = 3.0 × 10-971) for 2-stage Mendelian randomization.
Results: No association between ARA and colorectal polyp incidence was observed (OR = 1.00; 95% CI: 0.99, 1.00; p value = 0.50) within the UK Biobank (1,391 cases; 462,933 total).
Conclusions: Blood levels of ARA do not associate with colorectal polyp incidence in a general healthy population. Although not providing direct evidence, this work supports the contention that downstream lipid mediators, such as PGE2 rather than ARA itself, are key for polyp formation during early-stage colorectal carcinogenesis.
期刊介绍:
Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.