目的 采用孟德尔随机化（Mendelian randomization,MR）方法分析相对糖摄入量与乳腺癌的因果关系。方法 对相对糖摄入量与乳腺癌的全基因组关联研究（genome-wide association study,GWAS）数据进行MR分析,将与相对糖摄入量强相关的单核苷酸多态性（single nucleotide polymorphisms,SNPs）作为工具变量（instrumental variables,IV）,采用MR-Egger、加权中位数、逆方差加权（inverse-variance weighted,IVW）、简单模式及加权模式等5种分析方法评估相对糖摄入量与乳腺癌之间的因果关联。采用Cochran's Q检验检测异质性,MR-Egger回归进行多效性分析,“留一法”进行敏感性分析。结果 共筛选出9个与相对糖摄入量强相关的SNPs作为IV,IVW、MR-Egger、简单模式等5种方法均显示相对糖摄入量与乳腺癌之间不存在因果关系（P>0.05）;Cochran's Q检验显示存在一定的异质性（P<0.10）;MR-Egger回归多效性分析显示不存在多效性（P>0.05）;“留一法”敏感性分析显示MR分析结果具有稳定性。结论 相对糖摄入量与乳腺癌之间未发现因果关系,相对糖摄入量不是乳腺癌的风险因素。
Abstract
Objective To analyze the causal relationship between relative sugar intake and breast cancer using Mendelian randomization (MR). Methods The genome-wide association study (GWAS) data on relative sugar intake and breast cancer were analyzed by MR, and single nucleotide polymorphisms (SNPs) strongly associated with relative sugar intake were used as instrumental variables (IV), and five analysis methods were used to evaluate the causal relationship between relative sugar intake and breast cancer, including the MR-Egger, the weighted median, the inverse-variance weighted (IVW), the simple model and weighted model were used to assess the causal association between relative sugar intake and breast cancer using five analytical methods. Cochran's Q test was used to detect heterogeneity, MR-Egger regression for multivariate analysis, and “leave-one-out” method for sensitivity analysis. Results A total of nine SNPs strongly associated with relative sugar intake were screened as IV, and five methods, including IVW, MR-Egger, and simple model, showed that there was no causality between relative sugar intake and breast cancer (P>0.05); Cochran's Q test showed that there existed a certain degree of heterogeneity (P<0.10); and the multivariate analysis of MR-Egger regression revealed that The MR-Egger regression analysis showed that there was no pleiotropy (P>0.05); the sensitivity analysis of the “leave-one-out” method showed that the results of the MR analysis were stable. Conclusion There is no causal relationship between relative sugar intake and breast cancer, and relative sugar intake is not a risk factor for breast cancer.
关键词
乳腺癌 /
相对糖摄入量 /
孟德尔随机化 /
因果律 /
全基因组关联研究
Key words
breast cancer /
relative sugar intake /
mendelian randomization /
causal law /
genome-wide association study
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参考文献
[1] 王裕新, 潘凯枫, 李文庆.2022全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2024, 10(03): 1-16.
[2] LEI S, ZHENG R, ZHANG S, et al.Global patterns of breast cancer incidence and mortality: A population-based cancer registry data analysis from 2000 to 2020.[J]. Cancer Commun (Lond), 2021, 41(11): 1183-1194.
[3] 邬昊, 吕青. 全球及中国乳腺癌的流行病学趋势及防控启示: 2018-2022年《全球癌症统计报告》解读[J]. 中国普外基础与临床杂志, 2024, 31(07): 796-802.
[4] WANG X, SUN H, PAN S, et al.Causal relationships between relative intake from the macronutrients and alzheimer's disease: a two-sample mendelian randomization study.[J]. J Alzheimers Dis, 2022, 87(2): 665-673.
[5] LALIOTI A, VERZELETTI L, TIBERIO P, et al.Common misconceptions about diet and breast cancer: an unclear issue to dispel[J]. Cancers (Basel), 2024, 16(2): 306.
[6] EPNER M, YANG P, WAGNER RW, et al.. Understanding the link between sugar and cancer: an examination of the preclinical and clinical evidence[J]. Cancers (Basel), 2022, 14(24): 6042.
[7] JIANG Y, Pan Y, Rhea PR, et al.A sucrose-enriched diet promotes tumorigenesis in mammary gland in part through the 12-lipoxygenase pathway[J]. Cancer Res, 2016, 76(1): 24-29.
[8] PISHDAD S, JOOLA P, BOURBOUR F, et al.Association between different types of dietary carbohydrate and breast cancer[J]. Clin Nutr ESPEN, 2021, 46: 259-263.
[9] ROMANOS-NANCLARES A, COLLINS LC, HU FB, et al.Sugar-sweetened beverages, artificially sweetened beverages, and breast cancer risk: results from 2 prospective US cohorts[J]. J Nutr, 2021, 151(9): 2768-2779.
[10] FERENCE BA, HOLMES MV, SMITH GD.Using mendelian randomization to improve the design of randomized trials.[J]. Cold Spring Harb Perspect Med, 2021, 11(7): a040980.
[11] 于天琦, 徐文涛, 苏雅娜, 等. 孟德尔随机化研究基本原理、方法和局限性[J]. 中国循证医学杂志, 2021, 21(10): 1227-1234.
[12] JIANG L, ZHENG Z, FANG H, YANG J.A generalized linear mixed model association tool for biobank-scale data[J]. Nat Genet, 2021, 53(11): 1616-1621.
[13] MEDDENS SFW, DE VLAMING R, BOWERS P, et al.Genomic analysis of diet composition finds novel loci and associations with health and lifestyle[J]. Mol Psychiatry, 2021, 26(6): 2056-2069.
[14] HEMANI G, ZHENG J, ELSWORTH B, , et al. The MR-Base platform supports systematic causal inference across the human phenome.[J]. Elife, 2018, 7 7: e34408.
[15] BURGESS S, THOMPSON SG.Mendelian Randomization: Methods for Causal Inference Using Genetic Variants[M]. Florida: CRC Press, 2021.
[16] MOUNIER N, KUTALIK Z.Bias correction for inverse variance weighting Mendelian randomization.[J]. Genet Epidemiol, 2023, 47(4): 314-331.
[17] 王嘉琪, 唐伟, 黄晓, 等. 孟德尔随机化探究Omega-3脂肪酸与乳腺癌发病风险的因果关系[J]. 肿瘤防治研究, 2024, 51(07): 567-572.
[18] 刘宗超, 李哲轩, 张阳, 等.2020全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2021, 7(02): 1-14.
[19] XN L U, DU HZ, TF ZHANG.饮食模式或与乳腺癌风险相关[J]. 肿瘤代谢与营养电子杂志, 2023, 10(02): 229.
[20] DUCHAINE CS, DUMAS I, DIORIO C.Consumption of sweet foods and mammographic breast density: a cross-sectional study.[J]. BMC Public Health, 2014, 14: 554.
[21] 董浩. 膳食成分影响乳腺癌发病及预后[D]. 北京: 北京协和医学院, 2024.
[22] MIRICESCU D, TOTAN A, STANESCU-SPINU II, et al.PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects.[J]. Int J Mol Sci, 2020, 22(1): 173.
[23] 王佳妮, 李青, 徐兵河. 组蛋白去乙酰化酶抑制剂在HR阳性HER-2阴性晚期乳腺癌的研究进展[J]. 中国肿瘤临床, 2023, 50(17): 897-900.
[24] DORANS KS, BAZZANO LA, QI L, et al.Effects of a low-carbohydrate dietary intervention on hemoglobin A1c: a randomized clinical trial.[J]. JAMA JAMA Netw Open, 2022, 5(10): e2238645.
[25] 李露, 张贤益, 汤小芳, 等. 膳食中碳水化合物与代谢综合征的研究进展[J]. 食品科学, 2019, 40(07): 268-273.
[26] LI S, WEN CP, TU H, et al.Metabolic syndrome including both elevated blood pressure and elevated fasting plasma glucose is associated with higher mortality risk: a prospective study[J]. Diabetol Metab Syndr, 2025, 17(1): 72.
[27] NOLL PRES, NOLL M, ZANGIROLAMI-RAIMUNDO J, et al.Life habits of postmenopausal women: association of menopause symptom intensity and food consumption by degree of food processing[J]. Maturitas, 2022, 156: 1-11.
基金
国家级大学生创新训练计划项目“青年癌症患者生育力保存影响因素模型构建与实证研究”（S202410541124）; 湖南中医药大学研究生创新课题“青少年与青年癌症患者生育力保存决策优化方案构建与验证”（2024CX186）
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