Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? a systematic review and meta-analysis
Research output: Contribution to journal › Review article › peer-review
Colleges, School and Institutes
- Bristol Eye Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol
- School of Clinical Sciences at North Bristol
- Cardiff and Vale University Health board, University Hospital of Wales
- International Agency for Research on Cancer
- Cancer Research UK Cambridge Institute
- University of Bristol
- University Hospitals Bristol NHS Foundation Trust
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.
|Number of pages||32|
|Journal||Cancer Causes & Control|
|Publication status||Published - 30 Mar 2017|
- Animals, Disease Progression, Humans, Insulin-Like Growth Factor Binding Protein 1/metabolism, Insulin-Like Growth Factor Binding Protein 2/metabolism, Insulin-Like Growth Factor Binding Protein 3/metabolism, Insulin-Like Growth Factor I/metabolism, Insulin-Like Growth Factor II/metabolism, Male, Milk/adverse effects, Prostate/metabolism, Prostatic Neoplasms/metabolism, Risk