Genetic, Anthropometric, and Lifestyle Factors Associated with IGF-1 and IGFBP-3 Levels in Hispanic and Non-Hispanic White Women

Abstract

Circulating concentrations of IGF-I and IGFBP-3 are associated with risk of pre-menopausal breast cancer. Racial differences in levels of these factors have been reported, and determinants of IGF-I and IGFBP-3 levels within racial and ethnic groups are unclear. In this study we examine genetic, anthropometric, diet, and lifestyle factors that may predict serum levels of IGF-I and IGFBP-3 among Hispanic and non-Hispanic white women. A sample of healthy controls participating in the SHINE (Southwest Hormone, Insulin, Nutrition, and Exercise Study) case-control breast cancer in Arizona, Colorado, New Mexico, and Utah were included in these analyses. Subjects included 210 Hispanic and 284 non-Hispanic white women. Hispanic women had significantly lower levels of IGFBP-3 (mean=3764.3 mcg/ml) after adjusting for age, body size, physical activity, menopausal status, and dietary factors than non-Hispanic white women (mean = 4058.0 mcg/ml; p<0.01). The CC genotype of the -202 A>C polymorphism of the IGFBP3 gene was associated with lower IGFBP-3 levels in both ethnic groups. The frequency of the IGFBP3 C allele differed between Hispanic (0.65) and non-Hispanic white women (0.53), but serum levels of IGFBP-3 were lower for Hispanic women than non-Hispanic after accounting for IGFBP3 genotype. Body size indicators, vigorous physical activity, and dietary factors appeared to influence serum levels of IGF-1 and the ratio of IGF-1 to IGFBP-3 in pre-menopausal women more than in post-menopausal women. On the other hand, using aspirin/NSAIDs appeared to increase IGFBP-3 levels significantly among pre-menopausal Hispanic women. Results from this study suggest that differences in IGFBP-3 levels exist in Hispanic and non-Hispanic white women. These differences could be due to the combined effects of genetic and behavioral factors which could account for ethnic differences in the risk of breast cancer and other chronic diseases.

Prostate Cancer Risk in Relation to Selected Genetic Polymorphisms in Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3, and Insulin-like Growth Factor-I Receptor

“…This is consistent with results from other published studies to date among men and women, and among Caucasians and Asians (33,35,37,(43)(44)(45)(46)(47)(48), suggesting that this polymorphism may be a good surrogate in the evaluation of exposure of target organs to endogenous IGFBP-3 and a good marker for the evaluation of cancer risk. Two prior studies observed a weak and statistically imprecise elevation in risk of prostate cancer associated with having the C allele (39,49).…”

Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies

“…4 It was reported that IGFBP3 could play an anti-apoptotic role in Hs578T breast cancer cells. 43 Besides, body size, vigorous physical activity, and dietary factors could influence IGF1 and IGFBP3 molar ratio in pre-menopausal breast cancer women more than postmenopausal breast cancer women, 44 and they might account for the different roles of IGF1 and IGFBP3 in breast cancer according to menopausal status.…”

Association between IGF1 CA microsatellites and mammographic density, anthropometric measures, and circulating IGF-I levels in premenopausal Caucasian women

“…A positive association was found in one study [18], and no association was reported in two others [16,30]. Among studies that presented data for premenopausal women, results are also inconsistent with a positive association of the 19 allele at 5 0 and IGF-I levels suggested in one study, while no association, and an inverse association among oral contraceptive users only were also reported [10,18,31].…”