基于遗传预测的血浆磷脂花生四烯酸浓度与英国生物库和遗传联盟参与者的 10 个特定部位癌症：一项孟德尔随机研究。
Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants: A mendelian randomization study.
机构信息
Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
出版信息
Clin Nutr. 2021 May;40(5):3332-3337. doi: 10.1016/j.clnu.2020.11.004. Epub 2020 Nov 7.
BACKGROUND & AIMS: Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers.
METHODS
Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P = 3.0 × 10] and rs16966952 in PDXDC1 [P = 2.4 × 10]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n = 367,643), FinnGen consortium (n = 135,638), International Lung Cancer Consortium (n = 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254), Breast Cancer Association Consortium (n = 228,951), Ovarian Cancer Association Consortium (n = 66,450), and BioBank Japan (n = 212,453).
RESULTS
Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P = 6.3 × 10) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P = 3.5 × 10) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P = 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary.
CONCLUSION
These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit.
背景与目的
花生四烯酸（AA）可被环加氧酶和脂加氧酶代谢为促炎类二十烷酸，据实验研究表明，其可调节肿瘤细胞的增殖、分化和凋亡。我们采用孟德尔随机化设计，检验了这样一个假说，即较高的血浆磷脂 AA 浓度与 10 个特定部位癌症的风险增加有关。
方法
我们使用了与 Cohorts for Heart and Aging Research in Genomic Epidemiology 联盟中血浆磷脂 AA 浓度相关的两个遗传变异（FADS1 中的 rs174547 [P=3.0×10]和 PDXDC1 中的 rs16966952 [P=2.4×10]）作为遗传工具。这些变体与癌症的关联来自 UK Biobank（n=367643）、FinnGen 联盟（n=135638）、国际肺癌联盟（n=27209）、前列腺癌协会基因组协会（n=140254）、乳腺癌协会联盟（n=228951）、卵巢癌协会联盟（n=66450）和日本生物银行（n=212453）。
结果
较高的遗传预测血浆磷脂 AA 浓度与结直肠癌和肺癌风险增加有关。结果在不同数据源和变体中是一致的。AA 浓度每增加一个标准差的合并比值比为 1.08（95%CI 1.05-1.11；P=6.3×10），结直肠癌；1.07（95%CI 1.05-1.10；P=3.5×10），肺癌。遗传预测的 AA 浓度与食管癌呈正相关（比值比 1.09；95%CI 1.02-1.17；P=0.016），但与胃癌、胰腺癌、膀胱癌、前列腺癌、乳腺癌、子宫癌或卵巢癌无关。
结论
这些结果表明，AA 可能与结直肠癌和肺癌的发生有关，也可能与食管癌有关。应评估具有降低血浆 AA 特性的治疗方法的临床获益。
Zotero 插件