Insulin‐like growth factor pathway genes and blood concentrations, dietary protein and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

Abstract

It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested case-control studies within large North-American and European cohorts. Per allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (P<0.01), but not with IGFBP-3 concentrations (P>0.10) or with risk of prostate cancer (P>0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance (SSTR5 (somatostatin receptor 5) -rs197056 [uncorrected P for interaction, 0.001]; SSTR5-rs197057 [uncorrected P for interaction, 0.002]). We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein.

The association of plasma IGF-I with dietary, lifestyle, anthropometric, and early life factors in postmenopausal women

“…Others have also reported similar associations between total protein intake and circulating IGF-I in men, women, and children [3,4,[13][14][15][16][17][18]. Similarly, others have shown positive associations between dairy protein [3,4,14], milk [13,18], and dairy products [3,18] intakes and circulating IGF-I concentrations [19].…”

Dairy intake and semen quality among men attending a fertility clinic

“…While not part of our original hypothesis, this finding may reflect known effects of low-fat dairy intake on circulating insulin growth factor-1 (IGF-1) and insulin levels. Low-fat milk intake is associated with higher circulating levels of IGF-1 in free living populations (31, 32) and increases IGF-1 levels in feeding trials (33, 34). Intake of protein from animal sources, which appeared to account for the association between low-fat dairy and sperm concentration, increases post-prandial insulinemia in animal and human feeding experiments (35, 36).…”

Role of Environmental Chemicals, Processed Food Derivatives, and Nutrients in the Induction of Carcinogenesis

“…Additionally, high consumption of dairy products seems to increase IGF-1 level, implicated in prostate cancer risk [167,169], colon CSC proliferation [171], colon CSC chemoresistance [172] and acquisition of a glioma CSC malignant phenotype [173] (Figure 2). …”

“…Importantly, dairy product consumption is known to increase the insulin-like growth factor 1 (IGF-1) level, which has implication in the risk of prostate cancer [167,169]. The IGF-1 receptor/ligand system plays a crucial role in cancer cell progression and metastasis [170].…”