PO.CL01.19 · 临床研究
非裔美国成年人中循环鞘脂类与结直肠癌风险
Circulating sphingolipids and colorectal cancer risk in African American adults
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景:肥胖相关的代谢功能障碍可能通过鞘脂类通路促进结直肠癌变。神经酰胺及相关分子调节胰岛素抵抗、炎症和肠道干细胞增殖;然而,将循环鞘脂类与结直肠癌(CRC)相关联的前瞻性数据有限,尤其是在非裔美国人中。
方法:我们在南方社区队列研究(SCCS)中开展了一项巢式病例对照研究,纳入373例非裔美国CRC病例和373例匹配的对照参与者。靶向脂质组学分析定量了165种鞘脂类,包括78种神经酰胺、36种鞘磷脂、30种中性糖鞘脂、14种甘油磷酸胆碱、4种鞘氨醇碱-1-磷酸、4种鞘氨醇碱同系物以及一种神经酰胺-1-磷酸。条件逻辑回归估计了每个标准差(SD)对应的比值比(OR)和95% CI,并对年龄、性别、等分样本冻融循环次数、教育程度、体质指数、吸烟状况、体力活动、能量摄入、纤维摄入、红肉/加工肉摄入以及酒精摄入进行了校正。
结果:参与者年龄为54±9岁,55%为女性。在完全校正的模型中,若干种极长链神经酰胺和一种鞘磷脂在多重比较校正后(FDR q<0.05)显示出与CRC风险具有统计学意义的负相关,包括Cer(d16:1/23:0)、Cer(d16:1/22:0)、Cer(d17:1/22:0)、Cer(d17:1/23:0)、Cer(d18:2/23:0)和SM(d16:1/23:0)(每SD的OR范围为0.76至0.80,p范围为0.001至0.009)。一些先前与代谢性疾病相关的长链二氢神经酰胺和神经酰胺与CRC呈正相关,尽管结果未达到统计学意义(例如,dhCer(d18:0/18:0),OR 1.15,95% CI 0.98-1.35;Cer(d18:1/18:0),OR 1.08,95% CI 0.92-1.26)。
结论:诊断前的极长链神经酰胺分子在非裔美国人中显示出与CRC发病率的保护性关联。研究结果凸显了可用于CRC预防的潜在代谢可干预通路。
致谢:U01CA202979和U01CA272529
查看英文原文 English abstract
Background: Obesity‑related metabolic dysfunction may promote colorectal carcinogenesis through sphingolipid pathways. Ceramides and related species regulate insulin resistance, inflammation, and intestinal stem‑cell proliferation; however, prospective data linking circulating sphingolipids to colorectal cancer (CRC) are limited, particularly in African Americans.
Methods: We conducted a nested case-control study within the Southern Community Cohort Study (SCCS) including 373 African American CRC cases and 373 matched control participants. Targeted lipidomic analysis quantified 165 sphingolipids including 78 ceramides, 36 sphingomyelins, 30 neutral glycosphingolipids, 14 glycerophosphocholines, 4 sphingoid base‑1‑phosphates, 4 sphingoid base homologs, and one ceramide‑1‑phosphate. Conditional logistic regression estimated odds ratios (OR) and 95% CI per standard deviation (SD), adjusting for age, sex, number of aliquot freeze-thaw cycles, education, body mass index, smoking status, physical activity, energy intake, fiber intake, red/processed meat intake, and alcohol intake.
Results: Participants were aged 54±9 years, and 55% were female. In fully adjusted models, several very‑long‑chain ceramides and one sphingomyelin showed statistically significant inverse associations with CRC risk with adjustment for multiple comparisons at FDR q<0.05, including Cer(d16:1/23:0), Cer(d16:1/22:0), Cer(d17:1/22:0), Cer(d17:1/23:0), Cer(d18:2/23:0), and SM(d16:1/23:0) (OR per SD range 0.76 to 0.80, p range 0.001 to 0.009). Some long-chain dihydroceramides and ceramides previously linked to metabolic diseases were positively associated with CRC, though results did not reach statistical significance (e.g., dhCer(d18:0/18:0), OR 1.15, 95% CI 0.98-1.35; Cer(d18:1/18:0), OR 1.08, 95% CI 0.92-1.26).
Conclusions: Pre‑diagnostic very‑long‑chain ceramide species showed protective associations with CRC incidence in African Americans. Findings highlight potential metabolically actionable pathways for CRC prevention.
Acknowledgement: U01CA202979 and U01CA272529
利益披露 Disclosure
S. Salas, None..
S. Richardson, None..
D. Yu, None..
A. Maschek, None..
J. E. Cox, None..
J. Alvarez, None..
E. Onyegba, None..
M. Siddique, None..
S. Moore, None..
M. Gunter, None..
A. Ibele, None..
X. Shu, None..
S. A. Summers, None..
C. M. Ulrich, None..
M. Playdon, None.