Insulin and IGF In female colon, breast, uterine cancer

Project: Research project

Project Details


DESCRIPTION (provided by applicant): Increasing evidence indicates that high
serum insulin-like growth factor-1 (IGF-1) is associated with elevated risk of
colorectal, breast, and endometrial cancer. Three Insulin Resistance
Syndrome-related conditions, type 2 diabetes, obesity, and sedentary lifestyle,
are also associated with greater risk of these cancers, and hyperinsulinemia is
hypothesized to drive these relationships, at least in part. Insulin shares 40
percent homology with IGF-1, and biologic studies suggest both are mitogens.
However, few epidemiologic studies have evaluated cancer risk based on insulin
levels, and none have been prospective with sufficient sample size or adequate
control for confounders. Similarly, there are sparse epidemiologic data
regarding free IGF-1 and cancer, even though the unbound form is the main
bioactive component. A cross-sectional study by our group found free IGF-I more
strongly associated with breast cancer than total IGF-1. To provide definitive
evidence of their associations with cancer, a prospective study of insulin and
free IGF-1 is necessary. Therefore, the purpose of this application is to
determine the effects of high serum insulin and free IGF-1 on risk of incident
colorectal, breast and endometrial cancer in postmenopausal women. Specimens
and data will be obtained from the Observational Study of the Women's Health
Initiative (WHI), a large (n=93,725), ethnically and geographically diverse
cohort of postmenopausal women aged 50-79. We propose conducting a case-cohort
study, testing baseline serum for fasting glucose, insulin, total and free
IGF-1, IGF binding protein-3 (IGFBP-3), and total estradiol. Follow-up will
average 7 years, with cases excluded if diagnosed in the first 18 months. Our
specific aims are to study: (1) The independent effects of high serum insulin
and free IGF-1 on risk of colorectal (n=500), breast (n=900) and endometrial
cancers (n=300); (2) Among the subcohort (controls; n=900), the factors related
to levels of total IGF-1, free IGF-1, and IGFBP-3; (3) Whether type 2 diabetes
is an independent risk factor for colorectal, breast and endometrial cancers,
controlling for insulin resistance, IGF-1 and IGFBP-3.
Effective start/end date1/15/0212/31/07


  • Medicine(all)
  • Oncology
  • Cancer Research


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