Predictors of Variation in Serum IGFI and IGFBP3 Levels in Healthy African American and White Men

Hoyo, Cathrine; Grubber, Janet M.; Demark‐Wahnefried, Wendy; Lobaugh, Bruce; Jeffreys, Amy S.; Grambow, Steven C.; Marks, Jeffrey R.; Keku, T. O.; Walther, Phillip J; Schildkraut, Joellen M.

doi:10.1016/s0027-9684(15)30981-0

Cited by 8 publications

(5 citation statements)

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“…While some studies reported correlation with reduced IGF-I levels [23, 25], others found that the IGF-I (CA) 19 repeat did not predict plasma levels [27, 65]. However, these findings are consistent with those of our previous reports where the effects of the IGF-I (CA) 19 polymorphism on circulating concentrations of IGF-I varied considerably by race/ethnicity [66], and associated with prostate cancer risk [67]. A recent study in a Chinese population, further analyzed the potential causes of these ethnic differences and found that the IGF-I (CA) 19 repeat by itself is not the primary regulatory element of IGF-I expression [68].…”

Section: Discussionsupporting

confidence: 88%

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

Keku

Vidal

Oliver

et al. 2012

Cancer Causes Control

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Purpose Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)n repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. Methods Participants were African Americans (231cases, 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens, and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5′-exonuclease (Taqman) assay. The IGF-I (CA)n repeat was assayed by PCR, and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Results The IGF-I (CA)19 repeat was higher in White controls (50%) than African American controls (31%). Whites homozygous for the IGF-I (CA)19 repeat had a nearly two fold increase in risk of colon cancer (OR=1.77; 95%CI=1.15–2.73), but not African Americans (OR= 0.73, 95%CI 0.50–1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR= 0.49, 95%CI 0.28–0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p- trend < 0.05). Conclusions These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.

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Section: Discussionsupporting

confidence: 88%

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

Keku

Vidal

Oliver

et al. 2012

Cancer Causes Control

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“…Previous literature shows considerable inter-individual variation of IGF-1 4, 13, 14 and a relatively low intra-individual variation 15, 16 indicating that IGF-1 levels represent a relatively stable individual physiological characteristic. Therefore, sharp increases in IGF-1 in the aging population (against age-related decrease) may surface as a reflection of more complex underlying disturbances in GH/IGF-1 homeostasis.…”

Section: Discussionmentioning

confidence: 91%

Increase in circulating levels of IGF‐1 and IGF‐1/IGFBP‐3 molar ratio over a decade is associated with colorectal adenomatous polyps

Soubry

Il’yasova

Sedjo

et al. 2011

Intl Journal of Cancer

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High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risk of several cancers. Regarding colorectal cancer, these associations are generally weak. We hypothesized that an increase in IGF-1 over time would be a stronger risk factor for cancer-related outcomes than the actual levels. In this analysis we utilized existing data from the Insulin Resistance and Atherosclerosis Study (IRAS). Circulating IGF-1 levels and molar ratios of IGF-1 to IGF binding protein 3 (IGFBP-3) were measured at three time points, within a 10-year follow-up period. We examined the associations of increase of the two variables with the presence of colorectal adenoma at the end of follow-up among participants with normal glucose tolerance at baseline. This included 143 individuals, from which 24 were diagnosed with adenomatous polyps. Although the mean levels of IGF-1 and IGF-1/IGFBP-3 decline with age, approximately 30% of the participants showed an increase of at least fifteen percent (“ever increase”) in one or both of these variables, compared to baseline. We found a positive association between “ever increase” in IGF-1 o r IGF-1/IGFBP-3 and the presence of colorectal adenoma: ORs were 3.81 (95% CI: 1.30-10.8) and 2.83 (95% CI: 1.00-8.22), respectively. No association was found when analyzing the actual levels of both variables at any time point. Our data suggest that an increase in circulating IGF-1 or IGF-1/IGFBP-3 may represent a disturbed GH/IGF1 homeostasis, which could favor the development of precancerous lesions, such as colorectal adenoma.

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“…For example, factors such as obesity have been thought to cause variations in IGFBP-3. 78 This could be true considering the fact that we demonstrated this population to have an increased body mass index. 79 Also, IGFBP-3 could be working along with other factors associated with persistence of cervical lesions.…”

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confidence: 67%

Serum Lipids, Insulin-Like Growth Factor Binding Protein-3 and Treatment Outcomes in Women with and without Cervical Lesions in South Western Uganda: A Cohort Study

Ssedyabane,

Randall,

Tusubira

et al. 2023

PLMI

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There is a documented association between cervical cancer and metabolic syndrome. In this study, we determined the association between lipids, insulin-like growth factor binding protein-3 (IGFBP-3) and treatment outcomes for cervical lesions at Mbarara Regional Referral Hospital (MRRH) in south western Uganda. Patients and Methods: In this prospective cohort study, we recruited 94 cases and 94 controls at the cervical cancer clinic of MRRH, and followed them for 12 months. Cases were confirmed with cytology and/or histology. With consent, we collected demographic data and measured lipids and IGFBP-3 both at baseline and after 12 months. The lipid profile was measured using a Cobas 6000 Chemistry Analyzer, whereas IGFBP-3 was measured using a MAGLUMI fully automated chemiluminescence immunoassay analyzer. Abnormal values for lipids were defined using WHO recommended cut-offs. IGFBP-3 concentrations were divided into two categories of low concentration (<3.29 µg/mL) and raised concentration (≥3.29 µg/mL). Statistical analyses were conducted in STATA version 17 using logistic regression analysis. A p-value of <0.05 was taken to be statistically significant. Results:The average (mean ± SD) age of our participants was 38.7±8.2 years for controls and 34.5±7.8 years for cases. The average serum IGFBP-3 concentration was 3.769±1.098 µg/mL among cases with cleared lesions and 3.505±0.979 µg/mL among cases whose lesions persisted. A serum IGFBP-3 concentration of less than 3.291 µg/mL was likely to be associated with clearance of cervical lesions (AOR 1.65, p=0.67), although this was not statistically significant. A serum triglyceride concentration of 35-135 mg/dL was also likely to be associated with clearance of cervical lesions (AOR 2.41, p=0.46), although this was also not statistically significant. Conclusion:Although not statistically significant, reduced serum concentrations of IGFBP-3 and triglyceride may be associated with clearance of cervical lesions. Lipid management may be of benefit in the treatment of cervical lesions.

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Predictors of Variation in Serum IGFI and IGFBP3 Levels in Healthy African American and White Men

Cited by 8 publications

References 45 publications

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

Increase in circulating levels of IGF‐1 and IGF‐1/IGFBP‐3 molar ratio over a decade is associated with colorectal adenomatous polyps

Serum Lipids, Insulin-Like Growth Factor Binding Protein-3 and Treatment Outcomes in Women with and without Cervical Lesions in South Western Uganda: A Cohort Study

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