Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)?
A systematic review and meta-analysis
Harrison, S, Lennon, R, Holly, JMP, Higgins, J, Gardner, MP, Perks, C, Gaunt, T, Tan, V, Borwick, C, Emmett, P, Jeffreys, M, Northstone, K, Rinaldi, S, Thomas, S, Turner, S, Pease, A, Vilenchik, V, Martin, R & Lewis, S, 2017, Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)?: A systematic review and meta-analysis. Cancer Causes and Control.
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 analysed using meta-analysis where possible, with summary data presented otherwise.
Results: One hundred and seventy two studies met 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 standardised 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 tumour size, and contradictory evidence with regards to the effect of IGFBP-3 suppression on tumour progression.
Conclusion: IGF-I is a potential mechanism underlying the observed associations between milk intake and prostate cancer risk.
Full details in the University publications repository