Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis

Renehan, Andrew G; Zwahlen, Marcel; Minder, Christoph E.; O’Dwyer, Sarah T; Shalet, Stephen M; Egger, Matthias

doi:10.1016/s0140-6736(04)16044-3

Cited by 1,516 publications

(1,213 citation statements)

References 40 publications

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“…Circulating concentrations of IGF‐I and IGFBP‐3 have been associated with risk of type 2 diabetes, cardiovascular diseases, cancer, and mortality in epidemiological studies (Juul et al ., 2002; Vasan et al ., 2003; Renehan et al ., 2004; Kaplan et al ., 2007; Friedrich et al ., 2009; Burgers et al ., 2011; Rajpathak et al ., 2012). In animal models, diminished IGF‐I/insulin signaling has been associated with extended lifespans (Ziv & Hu, 2011), although the role of the IGF axis in human longevity remains inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

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SummaryThe growth hormone/insulin‐like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF‐related proteins including IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF‐I and IGFBP‐3 concentrations (IGF1, IGFBP3,GCKR,TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP‐3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF‐I and IGFBP‐3 concentrations. The IGF‐I‐decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity‐associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF‐I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF‐I‐ and IGFBP‐3‐associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF‐I and IGFBP‐3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity‐associated loci.

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Section: Introductionmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

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show abstract

“…Previous studies have found heterogeneity by sample media ( e.g . serum or plasma) or type of assay,2 and this should be taken into consideration in future studies. It is also not possible to rule out residual confounding; in particular we were unable to investigate potential confounding factors related to non‐steroidal anti‐inflammatory drugs, infections or birthweight.…”

Section: Discussionmentioning

confidence: 99%

Prediagnostic circulating concentrations of plasma insulin‐like growth factor‐I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Pérez-Cornago

Appleby

Tipper

et al. 2016

Intl Journal of Cancer

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Insulin‐like growth factor (IGF)‐I has cancer promoting activities. However, the hypothesis that circulating IGF‐I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF‐I concentration was measured in pre‐diagnostic plasma samples from a nested case–control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF‐I concentration was not associated with overall lymphoma risk (multivariable‐adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57–1.03], p trend = 0.06). There was no statistical evidence of heterogeneity in this association with IGF‐I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (p heterogeneity for all ≥ 0.05). There were no associations between IGF‐I concentration and risk for specific BCL subtypes, T‐cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF‐I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF‐I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF‐I concentrations with lymphoma subtypes.

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“…However, while low peripheral IGF‐1 is linked to less cancer (Renehan et al ., 2004), it is associated with increased risk for other age‐related diseases in humans (Sonntag et al ., 2012). These observations, coupled with recent evidence that daf2 mutants spend a proportionately greater time in a frail state, despite their longevity phenotype (Bansal et al ., 2015), further highlight the complexity of this axis.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, low IGF‐1 action is relevant to humans because of its link to less cancer risk (Renehan et al ., 2004), an observation that spurred the development of IGF‐1R antagonists as a clinical cancer treatment (Pollak, 2012). Furthermore, our group has reported on a novel, functional mutation in the human IGF‐1R gene ( R407H ) that is enriched in centenarians and results in attenuated IGF‐1R signaling (Suh et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

Central insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline

et al. 2015

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SummaryLow insulin‐like growth factor‐1 (IGF‐1) signaling is associated with improved longevity, but is paradoxically linked with several age‐related diseases in humans. Insulin‐like growth factor‐1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF‐1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole‐body insulin action in aging. Utilizing hyperinsulinemic‐euglycemic clamps, we show that old insulin‐resistant rats with age‐related declines in IGF‐1 level demonstrate markedly improved whole‐body insulin action, when treated with central IGF‐1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF‐1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF‐1 action in the brain and periphery provides a ‘balance’ between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at ‘tipping the balance’ of IGF‐1 action centrally are the optimal approach to achieve healthy aging and longevity in humans.

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Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis

Cited by 1,516 publications

References 40 publications

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Prediagnostic circulating concentrations of plasma insulin‐like growth factor‐I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Central insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline

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