摄入牛奶是否通过对胰岛素样生长因子（IGFs）的影响促进前列腺癌的发生或发展？一项系统综述和荟萃分析。
Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis.
作者信息
Harrison Sean, Lennon Rosie, Holly Jeff, Higgins Julian P T, Gardner Mike, Perks Claire, Gaunt Tom, Tan Vanessa, Borwick Cath, Emmet Pauline, Jeffreys Mona, Northstone Kate, Rinaldi Sabina, Thomas Stephen, Turner Suzanne D, Pease Anna, Vilenchick Vicky, Martin Richard M, Lewis Sarah J
机构信息
School of Social and Community Medicine, University of Bristol, Bristol, UK.
MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
出版信息
Cancer Causes Control. 2017 Jun;28(6):497-528. doi: 10.1007/s10552-017-0883-1. Epub 2017 Mar 30.
PURPOSE
To establish whether the association between milk intake and prostate cancer operates via the insulin-like growth factor (IGF) pathway (including IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3).
METHODS
Systematic review, collating data from all relevant studies examining associations of milk with IGF, and those examining associations of IGF with prostate cancer risk and progression. Data were extracted from experimental and observational studies conducted in either humans or animals, and analyzed using meta-analysis where possible, with summary data presented otherwise.
RESULTS
One hundred and seventy-two studies met the inclusion criteria: 31 examining the milk-IGF relationship; 132 examining the IGF-prostate cancer relationship in humans; and 10 animal studies examining the IGF-prostate cancer relationship. There was moderate evidence that circulating IGF-I and IGFBP-3 increase with milk (and dairy protein) intake (an estimated standardized effect size of 0.10 SD increase in IGF-I and 0.05 SD in IGFBP-3 per 1 SD increase in milk intake). There was moderate evidence that prostate cancer risk increased with IGF-I (Random effects meta-analysis OR per SD increase in IGF-I 1.09; 95% CI 1.03, 1.16; n = 51 studies) and decreased with IGFBP-3 (OR 0.90; 0.83, 0.98; n = 39 studies), but not with other growth factors. The IGFBP-3 -202A/C single nucleotide polymorphism was positively associated with prostate cancer (pooled OR for A/C vs. AA = 1.22; 95% CI 0.84, 1.79; OR for C/C vs. AA = 1.51; 1.03, 2.21, n = 8 studies). No strong associations were observed for IGF-II, IGFBP-1 or IGFBP-2 with either milk intake or prostate cancer risk. There was little consistency within the data extracted from the small number of animal studies. There was additional evidence to suggest that the suppression of IGF-II can reduce tumor size, and contradictory evidence with regards to the effect of IGFBP-3 suppression on tumor progression.
CONCLUSION
IGF-I is a potential mechanism underlying the observed associations between milk intake and prostate cancer risk.
目的
确定牛奶摄入量与前列腺癌之间的关联是否通过胰岛素样生长因子（IGF）途径（包括IGF-I、IGF-II、IGFBP-1、IGFBP-2和IGFBP-3）发挥作用。
方法
系统综述，整理所有相关研究的数据，这些研究考察了牛奶与IGF的关联，以及IGF与前列腺癌风险和进展的关联。数据从在人类或动物中进行的实验性和观察性研究中提取，并尽可能使用荟萃分析进行分析，其他情况则呈现汇总数据。
结果
172项研究符合纳入标准：31项研究考察了牛奶与IGF的关系；132项研究考察了人类中IGF与前列腺癌的关系；10项动物研究考察了IGF与前列腺癌的关系。有中等证据表明，循环中的IGF-I和IGFBP-3随着牛奶（和乳制品蛋白）摄入量的增加而升高（估计每增加1个标准差的牛奶摄入量，IGF-I增加0.10个标准差，IGFBP-3增加0.05个标准差）。有中等证据表明，前列腺癌风险随着IGF-I的升高而增加（随机效应荟萃分析，IGF-I每增加1个标准差，比值比为1.09；95%置信区间为1.03，1.16；n = 51项研究），随着IGFBP-3的升高而降低（比值比为0.90；0.83，0.98；n = 39项研究），但与其他生长因子无关。IGFBP-3 -202A/C单核苷酸多态性与前列腺癌呈正相关（A/C与AA相比的合并比值比为1.22；95%置信区间为0.84，1.79；C/C与AA相比的比值比为1.51；1.03，2.21，n = 8项研究）。未观察到IGF-II、IGFBP-1或IGFBP-2与牛奶摄入量或前列腺癌风险之间有强关联。从少数动物研究中提取的数据一致性较差。有额外证据表明，抑制IGF-II可减小肿瘤大小，而关于抑制IGFBP-3对肿瘤进展的影响存在相互矛盾的证据。
结论
IGF-I是牛奶摄入量与前列腺癌风险之间观察到的关联背后的潜在机制。
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