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Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women

Jernström, Helena LU ; Deal, Cheri; Wilkin, Françoise; Chu, William; Tao, Yuzhen; Majeed, Noreen; Hudson, Thomas; Narod, Steven A. and Pollak, Michael (2001) In Cancer Epidemiology Biomarkers & Prevention 10(4). p.377-384
Abstract
Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) vary considerably between normal individuals. Recent epidemiological studies have provided evidence that these levels are predictive of risk of several common cancers. To evaluate possible sources of variation of the levels of circulating IGF-I and IGFBP-3 in females, we studied specific candidate genetic and nongenetic factors in 311 nulliparous, premenopausal Caucasian women, 17-35 years of age. Women who used oral contraceptives (OC) had reduced levels of IGF-I (269 versus 301 ng/ml; P = 0.001 adjusted for age) and increased levels of IGFBP-3 (4213 versus 4009 ng/ml; P = 0.002, adjusted for age) compared with nonusers.... (More)
Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) vary considerably between normal individuals. Recent epidemiological studies have provided evidence that these levels are predictive of risk of several common cancers. To evaluate possible sources of variation of the levels of circulating IGF-I and IGFBP-3 in females, we studied specific candidate genetic and nongenetic factors in 311 nulliparous, premenopausal Caucasian women, 17-35 years of age. Women who used oral contraceptives (OC) had reduced levels of IGF-I (269 versus 301 ng/ml; P = 0.001 adjusted for age) and increased levels of IGFBP-3 (4213 versus 4009 ng/ml; P = 0.002, adjusted for age) compared with nonusers. The ratio of IGF-I:IGFBP-3 was associated with the dose of estrogen contained in the OC (P(trend) = 0.006, adjusted for age). We identified a novel single bp polymorphism in the promoter region of the gene encoding IGFBP-3. This polymorphism was related to the level of IGFBP-3 in the circulation. Mean IGFBP-3 levels were 4390, 4130, and 3840 ng/ml for the AA, AC, and CC genotypes, respectively (P(trend) = 0.006, adjusted for age and OC use). We observed no effect of a recently described polymorphism in the promoter region of the gene encoding IGF-I on the plasma IGF-I level, but there was evidence for a modifying effect of this locus on the influence of OC on the IGF-I level. Our results support the view that circulating IGF-I levels and IGFBP-3 levels are complex traits and are influenced by a number of interacting genetic and nongenetic factors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Epidemiology Biomarkers & Prevention
volume
10
issue
4
pages
377 - 384
publisher
American Association for Cancer Research
external identifiers
  • pmid:11319179
  • scopus:0034894561
ISSN
1538-7755
language
English
LU publication?
yes
id
0f22b4c3-69c9-4ac8-abe7-b58c9d7d5214 (old id 1120986)
alternative location
http://cebp.aacrjournals.org/content/10/4/377.long
date added to LUP
2008-06-30 16:47:44
date last changed
2018-05-29 10:36:21
@article{0f22b4c3-69c9-4ac8-abe7-b58c9d7d5214,
  abstract     = {Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) vary considerably between normal individuals. Recent epidemiological studies have provided evidence that these levels are predictive of risk of several common cancers. To evaluate possible sources of variation of the levels of circulating IGF-I and IGFBP-3 in females, we studied specific candidate genetic and nongenetic factors in 311 nulliparous, premenopausal Caucasian women, 17-35 years of age. Women who used oral contraceptives (OC) had reduced levels of IGF-I (269 versus 301 ng/ml; P = 0.001 adjusted for age) and increased levels of IGFBP-3 (4213 versus 4009 ng/ml; P = 0.002, adjusted for age) compared with nonusers. The ratio of IGF-I:IGFBP-3 was associated with the dose of estrogen contained in the OC (P(trend) = 0.006, adjusted for age). We identified a novel single bp polymorphism in the promoter region of the gene encoding IGFBP-3. This polymorphism was related to the level of IGFBP-3 in the circulation. Mean IGFBP-3 levels were 4390, 4130, and 3840 ng/ml for the AA, AC, and CC genotypes, respectively (P(trend) = 0.006, adjusted for age and OC use). We observed no effect of a recently described polymorphism in the promoter region of the gene encoding IGF-I on the plasma IGF-I level, but there was evidence for a modifying effect of this locus on the influence of OC on the IGF-I level. Our results support the view that circulating IGF-I levels and IGFBP-3 levels are complex traits and are influenced by a number of interacting genetic and nongenetic factors.},
  author       = {Jernström, Helena and Deal, Cheri and Wilkin, Françoise and Chu, William and Tao, Yuzhen and Majeed, Noreen and Hudson, Thomas and Narod, Steven A. and Pollak, Michael},
  issn         = {1538-7755},
  language     = {eng},
  number       = {4},
  pages        = {377--384},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women},
  volume       = {10},
  year         = {2001},
}