Article(id=1324050700187087654, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202511465, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1764086400000, receivedDateStr=2025-11-26, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793607886597, onlineDateStr=2026-11-02, pubDate=1778342400000, pubDateStr=2026-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793607886597, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793607886597, creator=13701087609, updateTime=1793607886597, updator=13701087609, issue=Issue{id=1324050669933572771, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='9', pageStart='1537', pageEnd='1728', issueExtLink='null', onlineDate='null', pubDate='1778342400000', pubDateStr='2026-05-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793607879384, creator='13701087609', updateTime=1793670100562, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324311644528050975, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324311644528050976, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1605, endPage=1612, ext={EN=ArticleExt(id=1324050700413580071, articleId=1324050700187087654, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Disease burden and causal association of breast cancer attributable to excessive red meat intake globally, columnId=1228016572783063333, journalTitle=Modern Preventive Medicine, columnName=Nutrition and Food Hygiene, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the spatiotemporal trends in the global disease burden of breast cancer attributable to excessive red meat intake from 1990 to 2021, explore the causal relationship between red meat consumption and breast cancer, and provide a scientific basis for nutritional interventions in breast cancer.

Methods

Based on data from the Global Burden of Disease (GBD) study, mortality and disability-adjusted life years (DALYs) were used as evaluation indicators. Joinpoint regression and age-period-cohort models were employed to analyze trends and effects. Mendelian randomization (MR) was utilized to infer the causal association between red meat consumption and breast cancer.

Results

The disease burden exhibited a distribution pattern characterized by “low in Africa and Asia, and medium-to-high in Europe, the Americas, and Oceania”. From 1990 to 2021, the age-standardized mortality rate and DALY rate decreased by 19.22% and 14.87%, respectively, with a slight increase observed after 2015. Between 2019 and 2021, indicators in both males and females showed a short-term increase. The average annual percentage changes in mortality and DALYs were -0.717% and -0.536%, respectively. The decline in mortality was slightly greater in females than in males, while the decline in DALYs was greater in males. The peak disease burden occurred in the 47.5-52.5 years age group, with a resurgence of risk observed in the 1992 birth cohort. MR analysis confirmed a causal relationship between high beef intake and breast cancer (univariate IVW OR=1.511; multivariable IVW OR=3.390), while no definitive association was found for pork or lamb.

Conclusion

The global disease burden of breast cancer attributable to excessive red meat intake has generally declined, though spatial and gender differences exist, along with a recent resurgence. Excessive beef consumption is a potential risk factor for breast cancer. Differentiated nutritional intervention strategies should be developed, focusing on controlling excessive beef intake and monitoring red meat consumption trends in younger cohorts.

, authors=Zi-yu WANG1, Zhao-cheng LIU2, Hui-yu ZHAO1, Jia-he GAO1, Xiao-ru XU2, Yang-xuan GONG2, Yu-xia ZHANG3, Li-ping ZHANG1, authorsList=Zi-yu WANG, Zhao-cheng LIU, Hui-yu ZHAO, Jia-he GAO, Xiao-ru XU, Yang-xuan GONG, Yu-xia ZHANG, Li-ping ZHANG, authorCompany=null, correspAuthors=Li-ping ZHANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1324050705778094906, articleId=1324050700187087654, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=全球红肉摄入过多所致乳腺癌疾病负担与因果关联研究, columnId=1228016573034721597, journalTitle=现代预防医学, columnName=营养与食品卫生, runingTitle=null, highlight=null, articleAbstract=
目的

分析1990—2021年全球红肉摄入过多所致乳腺癌疾病负担的时空趋势,探究红肉与乳腺癌的因果关系,为乳腺癌营养干预提供科学依据。

方法

基于全球疾病负担数据,以死亡率、伤残调整生命年(disability-adjusted life years,DALY)为评估指标,通过joinpoint回归、年龄-时期-队列模型分析趋势及效应,结合孟德尔随机化推断红肉与乳腺癌的因果关联。

结果

该疾病负担呈非洲、亚洲低,欧洲、美洲、大洋洲中高的分布特征;1990—2021年年龄标化死亡率、DALY分别下降19.2%、14.9%,2015年后小幅回升,2019—2021年男性、女性相关指标均短期上升;死亡率、DALY的年度平均变化百分比分别为-0.717%、-0.536%,女性死亡率降幅略高于男性,男性DALY降幅更高;47.5~52.5岁为负担峰值,1992年出生队列风险回升;孟德尔随机化证实牛肉过量摄入与乳腺癌发病存在因果关联(单/多变量IVW法OR=1.511、3.390),猪、羊肉则无明确关联。

结论

全球红肉摄入过多所致乳腺癌疾病负担整体下降,存在空间、性别差异及近期回升特征,牛肉过量是乳腺癌潜在危险因素。应制定差异化营养干预策略,管控牛肉过量摄入并关注年轻队列红肉消费趋势。

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王梓毓(2004—),女,硕士在读,研究方向:流行病与卫生统计学

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Chinese food composition table [M]. 7th ed.Beijing: Peking University Medical Press, 2023. 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Scientific research report supporting the dietary guidelines for Chinese residents(2022) [R]. Beijing: People's Medical Publishing House, 2022. (In Chinese), articleTitle=Scientific research report supporting the dietary guidelines for Chinese residents(2022), refAbstract=null), Reference(id=1324050722421093295, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, doi=null, pmid=null, pmcid=null, year=2020, volume=147, issue=5, pageStart=1354, pageEnd=1373, url=null, language=null, rfNumber=[30], rfOrder=38, authorNames=Chang VC, Cotterchio M, Bondy SJ, journalName=International Journal of Cancer. Journal International du Cancer, refType=null, unstructuredReference=Chang VC, Cotterchio M, Bondy SJ, et al. Iron intake, oxidative stress-related genes and breast cancer risk [J]. International Journal of Cancer. Journal International du Cancer, 2020, 147(5): 1354-1373., articleTitle=Iron intake, oxidative stress-related genes and breast cancer risk, refAbstract=null), Reference(id=1324050722500785072, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=10, pageStart=3601, pageEnd=null, url=null, language=null, rfNumber=[31], rfOrder=39, authorNames=Händel MN, Rohde JF, Jacobsen R, journalName=Nutrients, refType=null, unstructuredReference=Händel MN, Rohde JF, Jacobsen R, et al. Processed meat consumption and the risk of cancer:a critical evaluation of the constraints of current evidence from epidemiological studies [J]. Nutrients, 2021, 13(10): 3601., articleTitle=Processed meat consumption and the risk of cancer:a critical evaluation of the constraints of current evidence from epidemiological studies, refAbstract=null)], funds=[Fund(id=1324050717685724039, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, awardId=S202410760122, language=CN, fundingSource=新疆医科大学第十九期大学生创新训练计划项目(S202410760122), fundOrder=null, country=null), Fund(id=1324050717748638600, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, awardId=2025001FYJKS CZLKJZX650124499, language=CN, fundingSource=新疆维吾尔自治区卫生健康科技计划项目(2025)(2025001FYJKS CZLKJZX650124499), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1324050707644560187, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, xref=1., ext=[AuthorCompanyExt(id=1324050707652948796, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, companyId=1324050707644560187, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Institute of Medical Engineering Interdisciplinary Research, College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, Xinjiang 830017, China), AuthorCompanyExt(id=1324050707673920317, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, companyId=1324050707644560187, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.新疆医科大学医学工程技术学院医工交叉研究所,新疆 乌鲁木齐 830017)]), AuthorCompany(id=1324050707757806398, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, xref=2., ext=[AuthorCompanyExt(id=1324050707766195007, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, companyId=1324050707757806398, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.新疆医科大学基础医学院)]), AuthorCompany(id=1324050707854275392, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, xref=3., ext=[AuthorCompanyExt(id=1324050707862664001, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, companyId=1324050707854275392, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.乌鲁木齐妇幼保健医院临床营养科)])], figs=[ArticleFig(id=1324050714342863730, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Figure 1, caption=Spatial distribution analysis of the global burden of breast cancer caused by excessive red meat intake in 2021, figureFileSmall=3sfaXcBhO/8EQfkogk3mWg==, figureFileBig=k2yiUAXb+IQBJcPJrEtLoA==, tableContent=null), ArticleFig(id=1324050714430944115, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=图1, caption=2021 年全球因红肉摄入过多所致乳腺癌疾病负担空间分布分析

注:A为2021年全球归因于红肉摄入过多乳腺癌死亡分布;B为2021年全球归因于红肉摄入过多乳腺癌DALY分布;上述分类阈值基于2021年GSD数据的四分位数分布确定,并结合既往研究和公共卫生意义进行校准;底图采用中华人民共和国自然资源部标准地图,审图号为GS(2016)1666号,底图无修改;疾病负担数据来源于GBD 2021数据库。

, figureFileSmall=3sfaXcBhO/8EQfkogk3mWg==, figureFileBig=k2yiUAXb+IQBJcPJrEtLoA==, tableContent=null), ArticleFig(id=1324050714779071349, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Figure 2, caption=The changing trend of the global burden of breast cancer caused by excessive red meat intake, figureFileSmall=sE5bQthd8xWR2D+rL7XZDg==, figureFileBig=yR5jrhJRD1RHuJV+tXk0Sg==, tableContent=null), ArticleFig(id=1324050716477764472, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=图2, caption=全球因红肉摄入过多所致乳腺癌疾病负担变化趋势, figureFileSmall=sE5bQthd8xWR2D+rL7XZDg==, figureFileBig=yR5jrhJRD1RHuJV+tXk0Sg==, tableContent=null), ArticleFig(id=1324050716570039161, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Figure 3, caption=Joinpoint regression analysis of breast cancer attributable to excessive red meat intake globally, figureFileSmall=SZWdXnhIeI3eT/LqNLLAzg==, figureFileBig=13M3weWgAVjkmWOQviNvEQ==, tableContent=null), ArticleFig(id=1324050716658119546, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=图3, caption=全球因红肉摄入过多所致乳腺癌joinpoint回归分析

注:A为全球男性因红肉摄入过多所致乳腺癌死亡率的joinpoint回归分析;B为全球女性因红肉摄入过多所致乳腺癌死亡率的joinpoint回归分析;C为全球全性别因红肉摄入过多所致乳腺癌死亡率的joinpoint回归分析;D为全球男性因红肉摄入过多所致乳腺癌DALY的joinpoint回归分析;E为全球女性因红肉摄入过多所致乳腺癌DALY的joinpoint回归分析;F为全球全性别因红肉摄入过多所致乳腺癌DALY的joinpoint回归分析;*表示α=0.05时,APC的差异具有统计学意义。

, figureFileSmall=SZWdXnhIeI3eT/LqNLLAzg==, figureFileBig=13M3weWgAVjkmWOQviNvEQ==, tableContent=null), ArticleFig(id=1324050716750394235, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Figure 4, caption=Results of APC model analysis of global breast cancer mortality attributable to excessive red meat intake, figureFileSmall=+aFVZYtouP8MTGqGDwWRHQ==, figureFileBig=JgSs73uB0NVPvFS9lcVhog==, tableContent=null), ArticleFig(id=1324050716855251836, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=图4, caption=全球因红肉摄入过多所致乳腺癌死亡率的APC模型结果分析

注:A为年龄偏离;B为纵向年龄曲线;C为横断年龄曲线;D为时期偏离;E为拟合时间趋势;F为时期风险比;G为队列偏离;H为队列风险比;I为含净漂移的局部漂移。

, figureFileSmall=+aFVZYtouP8MTGqGDwWRHQ==, figureFileBig=JgSs73uB0NVPvFS9lcVhog==, tableContent=null), ArticleFig(id=1324050716930749309, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Figure 5, caption=APC model analysis of disability-adjusted life years for breast cancer attributable to excessive red meat intake globally, figureFileSmall=6GeAzLcnXC/20kgkZDGR4g==, figureFileBig=dR1Fomlj9BNIl6fT4HqmQg==, tableContent=null), ArticleFig(id=1324050717002052478, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=图5, caption=全球因红肉摄入过多所致乳腺癌DALY的APC模型结果分析

注:A为年龄偏离;B为纵向年龄曲线;C为横断年龄曲线;D为时期偏离;E为拟合时间趋势;F为时期风险比;G为队列偏离;H为队列风险比;I为含净漂移的局部漂移。

, figureFileSmall=6GeAzLcnXC/20kgkZDGR4g==, figureFileBig=dR1Fomlj9BNIl6fT4HqmQg==, tableContent=null), ArticleFig(id=1324050717073355647, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Table 1, caption=

Joinpoint regression analysis results of breast cancer caused by excessive red meat intake worldwide

, figureFileSmall=null, figureFileBig=null, tableContent=
指标人群分组AAPC(%,95% CI)P值
死亡率总体-0.717 0(-0.749 8~ -0.677 9)< 0.001
男性-0.516 0(-0.422 8~ -0.574 6)< 0.001
女性-0.656 0(-0.687 7~ -0.617 4)< 0.001
DALY总体-0.536 0(-0.577 7~ -0.503 3)< 0.001
男性-0.642 7(-0.544 0~ -0.708 0)< 0.001
女性-0.517 8(-0.558 8~ -0.485 4)< 0.001
), ArticleFig(id=1324050717144658816, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=表1, caption=

全球因红肉摄入过多所致乳腺癌joinpoint回归分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
指标人群分组AAPC(%,95% CI)P值
死亡率总体-0.717 0(-0.749 8~ -0.677 9)< 0.001
男性-0.516 0(-0.422 8~ -0.574 6)< 0.001
女性-0.656 0(-0.687 7~ -0.617 4)< 0.001
DALY总体-0.536 0(-0.577 7~ -0.503 3)< 0.001
男性-0.642 7(-0.544 0~ -0.708 0)< 0.001
女性-0.517 8(-0.558 8~ -0.485 4)< 0.001
), ArticleFig(id=1324050717241127809, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Table 2, caption=

Mendelian randomization of data source labeling for various types of red meat

, figureFileSmall=null, figureFileBig=null, tableContent=
GWAS ID性状年份(年)联盟/机构病例数对照数样本量SNPs数量
ukb-b-5640Pork intake2018MRC-IEU460 162—460 1629 851 867
ukb-b-14179Mutton intake2018MRC-IEU460 006—460 0069 851 867
ukb-b-2862Beef intake2018MRC-IEU461 053—461 0539 851 867
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MR红肉各种类数据来源标注

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GWAS ID性状年份(年)联盟/机构病例数对照数样本量SNPs数量
ukb-b-5640Pork intake2018MRC-IEU460 162—460 1629 851 867
ukb-b-14179Mutton intake2018MRC-IEU460 006—460 0069 851 867
ukb-b-2862Beef intake2018MRC-IEU461 053—461 0539 851 867
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Univariate mendelian randomization analysis of the causal relationship between red meat intake and breast cancer

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暴露因素水平多效性检验异质性检验
MR-Egger回归MR-PRESSOIVWMR-Egger法
Egger截距P值全局检验P值Q值P值Q值P值
牛肉摄入量0.0070.67421.9180.11019.1410.08518.8220.064
猪肉摄入量-0.0030.88216.9900.18014.1610.16614.1250.118
羊肉摄入量-0.0170.01458.7330.00254.5890.00343.8460.029
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红肉摄入与乳腺癌因果关系的单因素MR分析

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暴露因素水平多效性检验异质性检验
MR-Egger回归MR-PRESSOIVWMR-Egger法
Egger截距P值全局检验P值Q值P值Q值P值
牛肉摄入量0.0070.67421.9180.11019.1410.08518.8220.064
猪肉摄入量-0.0030.88216.9900.18014.1610.16614.1250.118
羊肉摄入量-0.0170.01458.7330.00254.5890.00343.8460.029
), ArticleFig(id=1324050717517951877, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=EN, label=Table 4, caption=

Multivariatble mendelian randomization analysis of red meat intake and breast cancer

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调整因素结局指标SNPs数量多变量IVW (95% CI)P值多变量MR-Egger法
OR (95%CI)
P值多变量
MR-Egger截距
水平多效性
检验P值
羊肉摄入量乳腺癌280.710(0.290~1.760)0.4600.650(0.210~2.050)0.464
牛肉摄入量143.390(1.470~7.860)0.0043.120(1.070~9.080)0.0360.0010.802
猪肉摄入量110.490(0.150~1.580)0.2300.460(0.130~1.630)0.234
), ArticleFig(id=1324050717585060742, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050700187087654, language=CN, label=表4, caption=

红肉摄入与乳腺癌的多变量MR分析

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调整因素结局指标SNPs数量多变量IVW (95% CI)P值多变量MR-Egger法
OR (95%CI)
P值多变量
MR-Egger截距
水平多效性
检验P值
羊肉摄入量乳腺癌280.710(0.290~1.760)0.4600.650(0.210~2.050)0.464
牛肉摄入量143.390(1.470~7.860)0.0043.120(1.070~9.080)0.0360.0010.802
猪肉摄入量110.490(0.150~1.580)0.2300.460(0.130~1.630)0.234
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全球红肉摄入过多所致乳腺癌疾病负担与因果关联研究
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王梓毓 1 , 刘兆成 2 , 赵慧宇 1 , 高家贺 1 , 徐潇洳 2 , 龚扬轩 2 , 张玉霞 3 , 张利萍 1
现代预防医学 | 营养与食品卫生 2026,53(9): 1605-1612
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现代预防医学 |营养与食品卫生 2026 , 53 (9) : 1605 -1612
全球红肉摄入过多所致乳腺癌疾病负担与因果关联研究
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王梓毓1, 刘兆成2, 赵慧宇1, 高家贺1, 徐潇洳2, 龚扬轩2, 张玉霞3, 张利萍1
作者信息
  • 1.新疆医科大学医学工程技术学院医工交叉研究所,新疆 乌鲁木齐 830017
  • 2.新疆医科大学基础医学院
  • 3.乌鲁木齐妇幼保健医院临床营养科
通讯作者:
张利萍,E-mail:
作者简介:

王梓毓(2004—),女,硕士在读,研究方向:流行病与卫生统计学

Disease burden and causal association of breast cancer attributable to excessive red meat intake globally
Zi-yu WANG1, Zhao-cheng LIU2, Hui-yu ZHAO1, Jia-he GAO1, Xiao-ru XU2, Yang-xuan GONG2, Yu-xia ZHANG3, Li-ping ZHANG1
Affiliations
  • Institute of Medical Engineering Interdisciplinary Research, College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, Xinjiang 830017, China
出版时间: 2026-05-10 doi: 10.20043/j.cnki.MPM.202511465
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目的

分析1990—2021年全球红肉摄入过多所致乳腺癌疾病负担的时空趋势,探究红肉与乳腺癌的因果关系,为乳腺癌营养干预提供科学依据。

方法

基于全球疾病负担数据,以死亡率、伤残调整生命年(disability-adjusted life years,DALY)为评估指标,通过joinpoint回归、年龄-时期-队列模型分析趋势及效应,结合孟德尔随机化推断红肉与乳腺癌的因果关联。

结果

该疾病负担呈非洲、亚洲低,欧洲、美洲、大洋洲中高的分布特征;1990—2021年年龄标化死亡率、DALY分别下降19.2%、14.9%,2015年后小幅回升,2019—2021年男性、女性相关指标均短期上升;死亡率、DALY的年度平均变化百分比分别为-0.717%、-0.536%,女性死亡率降幅略高于男性,男性DALY降幅更高;47.5~52.5岁为负担峰值,1992年出生队列风险回升;孟德尔随机化证实牛肉过量摄入与乳腺癌发病存在因果关联(单/多变量IVW法OR=1.511、3.390),猪、羊肉则无明确关联。

结论

全球红肉摄入过多所致乳腺癌疾病负担整体下降,存在空间、性别差异及近期回升特征,牛肉过量是乳腺癌潜在危险因素。应制定差异化营养干预策略,管控牛肉过量摄入并关注年轻队列红肉消费趋势。

乳腺癌  /  红肉摄入过多  /  疾病负担  /  年龄-时期-队列
Objective

To analyze the spatiotemporal trends in the global disease burden of breast cancer attributable to excessive red meat intake from 1990 to 2021, explore the causal relationship between red meat consumption and breast cancer, and provide a scientific basis for nutritional interventions in breast cancer.

Methods

Based on data from the Global Burden of Disease (GBD) study, mortality and disability-adjusted life years (DALYs) were used as evaluation indicators. Joinpoint regression and age-period-cohort models were employed to analyze trends and effects. Mendelian randomization (MR) was utilized to infer the causal association between red meat consumption and breast cancer.

Results

The disease burden exhibited a distribution pattern characterized by “low in Africa and Asia, and medium-to-high in Europe, the Americas, and Oceania”. From 1990 to 2021, the age-standardized mortality rate and DALY rate decreased by 19.22% and 14.87%, respectively, with a slight increase observed after 2015. Between 2019 and 2021, indicators in both males and females showed a short-term increase. The average annual percentage changes in mortality and DALYs were -0.717% and -0.536%, respectively. The decline in mortality was slightly greater in females than in males, while the decline in DALYs was greater in males. The peak disease burden occurred in the 47.5-52.5 years age group, with a resurgence of risk observed in the 1992 birth cohort. MR analysis confirmed a causal relationship between high beef intake and breast cancer (univariate IVW OR=1.511; multivariable IVW OR=3.390), while no definitive association was found for pork or lamb.

Conclusion

The global disease burden of breast cancer attributable to excessive red meat intake has generally declined, though spatial and gender differences exist, along with a recent resurgence. Excessive beef consumption is a potential risk factor for breast cancer. Differentiated nutritional intervention strategies should be developed, focusing on controlling excessive beef intake and monitoring red meat consumption trends in younger cohorts.

Breast cancer  /  Excessive red meat intake  /  Disease burden  /  Age-period-cohort
王梓毓, 刘兆成, 赵慧宇, 高家贺, 徐潇洳, 龚扬轩, 张玉霞, 张利萍. 全球红肉摄入过多所致乳腺癌疾病负担与因果关联研究. 现代预防医学, 2026 , 53 (9) : 1605 -1612 . DOI: 10.20043/j.cnki.MPM.202511465
Zi-yu WANG, Zhao-cheng LIU, Hui-yu ZHAO, Jia-he GAO, Xiao-ru XU, Yang-xuan GONG, Yu-xia ZHANG, Li-ping ZHANG. Disease burden and causal association of breast cancer attributable to excessive red meat intake globally[J]. Modern Preventive Medicine, 2026 , 53 (9) : 1605 -1612 . DOI: 10.20043/j.cnki.MPM.202511465
2021年全球疾病负担(Global Burden of Disease,GBD)研究显示,红肉摄入过多为乳腺癌首要可改变危险因素,可导致全球81 506例乳腺癌归因死亡(占12.072%)、2 451 719例归因伤残调整寿命年(disability-adjusted life years,DALY,占11.864%),人群归因死亡率与DALY率分别为1.033/10万、31.068/10万[1]。既往研究多关注红肉与乳腺癌的整体关联,缺乏对不同红肉种类的特异性效应及疾病负担长期趋势的系统解析。本研究基于1990—2021年GBD数据,采用多模型整合分析,系统探讨红肉过量相关乳腺癌疾病负担的时空分布特征,并明确不同红肉类型与乳腺癌的因果关联,为乳腺癌精准营养防控提供科学依据。
本研究疾病负担与人口统计学数据来源于2021年GBD数据库(https://vizhub.healthdata.org/gbd-results/)[2]。红肉摄入标准参照GBD研究统一界定:未加工红肉日均摄入量>23 g/d(95% UI:18~27 g/d)则视为过量摄入。该阈值经剂量-反应荟萃分析验证。未加工红肉为猪肉、牛肉、羊肉等哺乳动物肌肉,不包含禽肉、鱼类、蛋类及加工肉制品。红肉摄入量数据来自英国生物样本库(UK Biobank)队列,该队列包括每种肉类类型的460 162、460 006和461 053名欧洲血统个体(http://www.nealelab.is/uk-biobank)。乳腺癌数据来自乳腺癌协会联合会,含122 977例病例和105 974例对照[3]。
线性回归趋势拟合过程以年份为自变量(x)、对应指标数值为因变量(y),构建回归方程y=ax+b,通过最小二乘法求解回归系数。以斜率a量化指标年度平均变化趋势,结合折线图可视化结果,依托数据拐点划分研究阶段,对比指标回归结果差异,解析疾病负担演变规律。
本研究采用Joinpoint 5.3.0.0软件分析红肉摄入过多所致乳腺癌的年龄标化死亡率(age-standardized mortality rate,ASMR),年龄标准化DALY率(age standardized DALYs rate,ASDR)趋势,分析前对数据进行了自然对数变换,以满足模型假设,通过网格搜索确定连接点位置,采用置换检验和贝叶斯准则优化模型[4-5]。通过计算年度变化百分比(annual percentage change,APC)、平均年度变化百分比(average annual percentage change,AAPC)及其95%置信区间评估趋势变化[6-7]。
年龄-时期-队列(age-period-cohort,APC)模型用于区分年龄、时期和出生队列对健康结局的独立影响[8]。本研究基于对数线性回归构建模型,其基本形式为:
其中μij为第i个年龄组在第j个时期的结局变量,α为截距,、、分别表示年龄、时期和队列的效应,εij为随机误差,且满足k=时期j-年龄i的队列关系[9-10]。
本研究采用两样本MR设计,分析猪肉、羊肉、牛肉摄入与乳腺癌发病风险的因果关联,以控制观察性研究的混杂偏倚与反向因果。MR以与暴露密切相关且不受传统混杂因素干扰的遗传变异[主要为单核苷酸多态性(single nucleotide polymorphisms,SNPs)]作为工具变量,用于推断暴露与结局的因果关系[11]。本研究选取与红肉摄入量显著相关的SNPs作为工具变量[12],利用基因型在配子形成阶段即已固定、且独立于后天混杂因素与反向因果的特性,无偏估计暴露因素对结局变量的因果效应。通过单变量MR(uvMR)评估红肉摄入对乳腺癌的独立因果效应,并采用多变量MR(mvMR)校正膳食及生活方式等混杂,进一步分析其直接因果效应。
为保障结果稳健性,本研究开展系列敏感性分析:采用Cochran Q检验工具变量异质性,MR-Egger回归截距项评估水平多效性,MR-PRESSO法识别并剔除异常位点,以验证因果关联的稳定性。
本研究采用GBD 2021数据,分析1990—2021年204个国家和地区红肉摄入过多所致乳腺癌的死亡率、DALY、ASMR、ASDR,年龄按5岁间隔分为25~29岁至≥95岁共14组。
MR分析中工具变量筛选标准[13-14]:首先,将与猪肉、羊肉或牛肉摄入量显著相关的SNPs(P<5×10-8)确定为潜在工具变量[14]。为确保所选SNP的独立性,采用严格参数进行连锁不平衡聚类(LDR2<0.001, kb=10 000)。通过数据协调函数排除模糊性回文SNP。计算剩余各SNPs的F统计量(F=β2/se2),剔除F值<10的变异以减少弱工具变量偏倚[15]。
红肉摄入过多所致乳腺癌疾病负担存在显著洲际差异。非洲、亚洲为低负担地区,该区域的莫桑比克、也门、阿富汗、索马里及印度,其死亡率(<0.3/10万)与DALY率(4.09/10万~10.26/10万)均落入全球极低水平区间。相反,欧洲、美洲及大洋洲为中高负担地区,塞尔维亚、希腊等国的死亡率处于3.62/10万~6.6/10万的中等区间,库克群岛、摩纳哥、巴哈马等国家/地区的DALY率则显著偏高,其中库克群岛的DALY率(156.68/10万)为全球各国家/地区最高。见图1。
1990—2021年全球该疾病ASMR与ASDR呈现总体下降趋势且存在阶段性波动。ASMR从1.16/10万降至0.937/10万,累积下降19.2%,年均下降0.62%,趋势斜率为-0.009/年;ASDR从33.61/10万降至28.61/10万,累积下降14.9%,年均下降0.48%,趋势斜率为-0.237/年,两者均于2015年后小幅回升。见图2。
joinpoint回归分析进一步揭示了红肉摄入过多所致乳腺癌疾病负担的性别差异与趋势转折特征,女性ASMR整体降幅略高于男性,而男性ASDR降幅高于女性。见表1、图3。
不同阶段ASMR趋势同样存在性别差异。男性在1990—2001、2004—2009和2019—2021年呈显著上升趋势,仅2001—2004和2009—2019年呈非显著下降;女性除1990—1993年无统计学变化外,1993—2002、2002—2006和2006—2014年持续显著下降,无明显上升阶段。
ASDR的性别差异与ASMR既有共性也有区别。男性与自身ASMR趋势相似,1990—2001、2004—2009和2019—2021年显著上升,其余阶段非显著下降;女性则在1994—2002、2002—2006和2006—2013年显著下降,仅2019—2021年出现显著上升。
死亡率与DALY均呈显著长期下降趋势,死亡率净漂移(-0.837%/年)略快于DALY(-0.787%/年)。Wald检验均拒绝NetDrift=0假设(死亡率:χ2=1 182.040,P<0.001;DALY:χ2=651.910,v=1,P<0.001)。年龄、时期及队列效应均存在独立且显著的异质性(均P<0.001)。模型各参数标准差均接近0,提示估计精度高、拟合稳定;时期与队列效应对死亡率及DALY均呈正向影响。见图4、5。
年龄效应呈非线性特征。死亡率与DALY年龄偏离值随年龄增长升至峰值(死亡率为47.5~52.5岁,DALY为52.5岁)后下降,97.5岁转为负值;死亡率年龄曲线呈指数上升,DALY曲线先快速上升、后趋稳再升高,横断面趋势更为显著。
时期偏离值整体波动下降,2010年达谷值,2012年后回升,2020年时期偏离值分别为0.018、0.020;以2005年为参照,2020年时期RR分别为0.900、0.906。队列偏离值呈同步波动趋势,1992年出生队列风险回升(死亡率 RR=0.884,DALY RR=0.895)。
局部漂移显示,死亡率自27.5岁、DALY自37.5岁后进入负向区间,47.5岁后趋于稳定,97.5岁略有回升。各指标95% CI多不重叠且不包含0,组间差异与趋势均具有统计学意义。
本研究选用UKB数据,在单变量MR分析中,采用MR-PRESSO法筛查并剔除离群SNPs;剔除rs1421085、rs62396185、rs12247907、rs7791463共4个位点后,以逆方差加权法(inverse variance weighting,IVW)估计因果效应。结果显示,牛肉摄入量与乳腺癌发病风险存在显著因果关联,Cochran Q检验与MR-Egger截距检验未提示存在异质性或水平多效性。见表2、3。
猪肉、羊肉摄入量的MR分析同样经MR-PRESSO剔除离群SNPs(猪肉:rs11211124;羊肉:rs9379832、rs35797675)后行IVW估计,未发现二者与乳腺癌发病风险存在统计学意义的因果关联。
多变量MR分析在校正牛肉、猪肉及羊肉摄入量后进一步证实,牛肉摄入量仍与乳腺癌发病风险显著相关,见表4。IVW结果显示,遗传预测的牛肉摄入量每增加1个单位,乳腺癌发病风险显著升高,MR-Egger结果方向与显著性一致。本研究未发现猪肉或羊肉摄入量与乳腺癌存在因果关联的证据。
本研究基于1990—2021年GBD数据,整合疾病负担分析、joinpoint回归、APC模型及MR模型,构建“现象描述-拐点定位-效应分解-因果验证”递进式研究框架,系统解析红肉摄入过多所致乳腺癌疾病负担的时空特征、人群差异及因果关联,为乳腺癌精准营养防控提供多维度科学依据[16]。结果显示,全球红肉相关乳腺癌疾病负担存在显著空间异质性、时间波动及性别差异,且牛肉摄入过量与乳腺癌发病存在明确因果关联。整体下降趋势证实防控成效,但近期反弹、队列回升等结构性风险更值得关注。
空间分布上,红肉相关乳腺癌疾病负担呈“非洲、亚洲较低,欧洲、美洲、大洋洲较高”格局,与各地区膳食结构、经济发展水平密切相关。亚洲、非洲国家以植物性饮食为主,红肉消费偏低,疾病负担较轻[17];欧洲、美洲及大洋洲国家未加工红肉(尤其是牛肉)摄入总量偏高,其含有的杂环胺、多环芳烃等致癌物(多由高温烹饪未加工红肉产生)可升高乳腺癌发病风险[18]。库克群岛、摩纳哥等高负担地区因红肉摄入过多、诊疗体系不完善,导致确诊偏晚、DALY升高,提示需同步强化膳食干预与医疗服务建设[19]。
时间趋势显示,1990—2021年全球红肉相关乳腺癌ASMR与ASDR整体下降,得益于筛查普及、诊疗优化及膳食指导推广[20],验证了宏观防控策略的有效性;但2015年后小幅回升,2019—2021年受新冠疫情影响,筛查中断、未加工红肉居家烹饪频次增加、摄入量上升,疾病负担阶段性反弹,提示干预不可松懈。Joinpoint回归显示存在明显性别差异,提示需制定分性别精准防控策略。
APC模型解析显示,疾病负担在47.5~52.5岁达峰值,与更年期激素变化、乳腺组织对致癌因素敏感性升高有关[21-22];高龄人群负担快速上升,需加强干预。时期效应波动下降印证公共卫生措施有效;1992年出生队列风险回升,与年轻人群西式饮食及红肉消费增加一致[23],预示未来防控压力可能回升。Joinpoint识别的拐点(女性2010年、全球2012年、男性2014年)与APC时期效应趋势高度吻合,提示拐点后疾病负担反弹与年轻队列牛肉摄入增加相关。
MR分析证实,牛肉摄入过量是乳腺癌发病的潜在危险因素,而猪肉、羊肉摄入与乳腺癌无明确统计学因果关联[24]。牛肉中饱和脂肪酸、血红素铁含量显著高于猪肉、羊肉[25-29],可通过炎症、氧化应激及DNA损伤升高发病风险;且猪肉、羊肉加工比例低、烹饪温度温和,或为因果效应存在差异的关键原因。多变量MR进一步排除混杂,验证牛肉与乳腺癌因果关系稳健性,为精准干预提供靶点。
各模型结果相互验证:APC模型提示时期与队列效应驱动疾病负担趋势,MR证实牛肉为关键危险因素,并解释47.5~52.5岁年龄峰值的潜在机制[30-31],强化效应分解结果可靠性。
本研究存在局限性。数据主要来源于欧洲血统人群,普适性有待多种族队列验证;未充分纳入社会经济、教育及其他膳食混杂因素;MR仍存在残余多效性等偏倚风险;APC模型受年龄-时期-队列共线性影响,效应估计存在一定不确定性;未覆盖马肉等小众红肉,羊肉工具变量存在水平多效性,需扩大样本并优化工具变量进一步校正。
综上,1990—2021年全球红肉摄入相关乳腺癌疾病负担整体下降,但空间异质性、性别差异及近期反弹趋势仍需重视,牛肉摄入过量是乳腺癌重要危险因素。未来应实施区域差异化膳食干预:高消费地区严控加工牛肉摄入,推广优质蛋白替代;低负担但消费上升地区加强早期营养教育;重点针对47.5~52.5岁女性及1992年后出生队列开展靶向膳食指导。后续需纳入多种族队列,开展多中心前瞻性研究,深入解析牛肉成分与乳腺癌的分子机制,为精准营养防控提供更高等级证据。
  • 新疆医科大学第十九期大学生创新训练计划项目(S202410760122)
  • 新疆维吾尔自治区卫生健康科技计划项目(2025)(2025001FYJKS CZLKJZX650124499)
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2026年第53卷第9期
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doi: 10.20043/j.cnki.MPM.202511465
  • 接收时间:2025-11-26
  • 首发时间:2026-11-02
  • 出版时间:2026-05-10
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  • 收稿日期:2025-11-26
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新疆医科大学第十九期大学生创新训练计划项目(S202410760122)
新疆维吾尔自治区卫生健康科技计划项目(2025)(2025001FYJKS CZLKJZX650124499)
作者信息
    1.新疆医科大学医学工程技术学院医工交叉研究所,新疆 乌鲁木齐 830017
    2.新疆医科大学基础医学院
    3.乌鲁木齐妇幼保健医院临床营养科

通讯作者:

张利萍,E-mail:
参考文献
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https://castjournals.cast.org.cn/joweb/xdyfyx/CN/10.20043/j.cnki.MPM.202511465
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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