Kuang Xiaogen, Wu Bingquan, Hu Dan, Matsika Juliet, Cheng Chunliang, Xiao Jiatong, Cai Zhiyong, Li Mingyong, Chen Jinbo, Zhou Weimin, Liu Bolong
Departments of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
Discov Oncol. 2025 Jul 1;16(1):1226. doi: 10.1007/s12672-025-03010-3.
This study used Mendelian randomization (MR) to investigate the causal association between circulating fatty acids (FAs) and the incidence of 10 human cancer types.
Single nucleotide polymorphisms (SNPs) significantly associated with circulating FAs were selected from 500,000 UK Biobank blood samples and 114,999 plasma samples from a large GWAS. Summary-level data on 174,006 cancer patients were obtained from the FinnGen biobank. The inverse variance weighted method was used for causal estimation, with additional analyses including MR-Egger regression, weighted median, weighted mode, Cochrane Q test, MR-PRESSO global test, and leave-one-out analyses. Multivariable Mendelian randomization (MVMR) was applied to adjust for potential confounders.
This study found a genetically causal effect of polyunsaturated FAs on kidney cancer incidence (OR: 1.528; 95% CI 1.164-2.266; P = 0.001), which remained significant after Bonferroni adjustment. The causal impact of omega-6, omega-3, and linoleic acid on kidney cancer risk was also observed (omega-6: OR = 1.586, P = 0.002; omega-3: OR = 1.311, P = 0.014; linoleic acid: OR = 1.527, P = 0.007). MVMR confirmed the consistent causal relationship (OR = 1.553, P = 0.0047) after adjusting for multiple variables. Results were validated in a larger cohort.
Higher circulating polyunsaturated FAs, especially omega-6, were associated with an increased risk of kidney cancer. Suggestive associations were found in small cell lung, rectal, bladder, pancreatic, and esophageal cancer.
本研究采用孟德尔随机化（MR）方法来探究循环脂肪酸（FAs）与10种人类癌症类型发病率之间的因果关系。
从500,000份英国生物银行血样和来自一项大型全基因组关联研究（GWAS）的114,999份血浆样本中筛选出与循环脂肪酸显著相关的单核苷酸多态性（SNPs）。从芬兰基因库获得了174,006名癌症患者的汇总数据。采用逆方差加权法进行因果估计，其他分析包括MR-Egger回归、加权中位数、加权众数、Cochrane Q检验、MR-PRESSO全局检验和留一法分析。应用多变量孟德尔随机化（MVMR）来调整潜在的混杂因素。
本研究发现多不饱和脂肪酸对肾癌发病率存在基因因果效应（比值比：1.528；95%置信区间1.164 - 2.266；P = 0.001），经Bonferroni校正后仍具有显著性。还观察到ω-6、ω-3和亚油酸对肾癌风险的因果影响（ω-6：比值比 = 1.586，P = 0.002；ω-3：比值比 = 1.311，P = 0.014；亚油酸：比值比 = 1.527，P = 0.007）。多变量孟德尔随机化在调整多个变量后证实了一致的因果关系（比值比 = 1.553，P = 0.0047）。结果在更大的队列中得到验证。
循环中多不饱和脂肪酸水平升高，尤其是ω-6，与肾癌风险增加有关。在小细胞肺癌、直肠癌、膀胱癌、胰腺癌和食管癌中发现了提示性关联。
