Article

Body Size in Early Life and Adult Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3

Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
American journal of epidemiology (Impact Factor: 4.98). 08/2011; 174(6):642-51. DOI: 10.1093/aje/kwr123
Source: PubMed

ABSTRACT Body size in early life has been associated with breast cancer risk. This may be partly mediated through the insulin-like
growth factor (IGF) pathway. The authors assessed whether birth weight, body fatness at ages 5 and 10 years, and body mass
index (BMI; weight (kg)/height (m)2) at age 18 years were associated with plasma concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth
factor binding protein 3 in 6,520 women aged 32–70 years at blood draw from the Nurses’ Health Study (1990–2006) and Nurses’
Health Study II (1997–2005). Birth weight, body fatness in childhood, and BMI at age 18 years were inversely associated with
adult IGF-1 levels. For example, IGF-1 levels were 11.9% lower in women who reported being heaviest at age 10 years than in
those who were leanest at age 10 (P-trend < 0.0001). Further, women who reported their birth weight as ≥10 pounds (≥4.5 kg) (vs. <5.5 pounds (<2.5 kg)) had 7.9%
lower IGF-1 levels (P-trend = 0.002). Women whose BMI at age 18 years was ≥30 (vs. <20) had 14.1% lower IGF-1 levels (P-trend < 0.0001). Similar inverse associations were observed for insulin-like growth factor binding protein 3. These observations
did not vary by adult BMI or menopausal status at blood draw. These findings suggest that altered IGF-1 levels in adulthood
may be a mechanism through which early-life body size influences subsequent breast cancer risk.

Download full-text

Full-text

Available from: Eva S Schernhammer, Jul 05, 2015
0 Followers
 · 
142 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Simple prevention messages based on understandable biologic principles are likely to be adopted. The long-held premise that postmenopausal obesity elevates, but premenopausal obesity reduces, risk for breast cancer is confusing to the public. Furthermore, decades of positive energy balance may be difficult to suddenly reverse at the time of the menopause. In this issue (beginning on page 583), Cecchini et al. suggest that obesity may also be a risk factor for pre-menopausal women 35 and older who have additional risk factors for breast cancer. Although the relative impact of dysregulated energy metabolism depends on many factors including age, hormonal milieu, and competing risk factors, as well as how it is measured, avoiding weight gain after age 30 is increasingly being recognized as a simple way to reduce risk of breast cancer.
    Cancer Prevention Research 04/2012; 5(4):511-4. DOI:10.1158/1940-6207.CAPR-12-0088 · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although earlier studies have indicated an inverse association between corpulence during childhood and the risk for breast cancer in adulthood, no study had evaluated body shape at different ages or body shape evolution in relation to the risk for breast cancer defined by menopausal status and hormone receptor status. Hazard ratios (HR) were estimated using multivariate Cox models in 81 089 women from the French E3N cohort to evaluate the risk for breast cancer associated with body shape (Sørensen's scale) at ages 8, menarche, 20-25, and 35-40 years. Six lifetime body shape trajectories were also estimated according to Nagin's approach to group-based trajectory modeling, and were analyzed in relation to the risk for breast cancer. During follow-up, 3573 breast cancer cases were diagnosed. At age 8 and at menarche, an increasing size of the body was associated with a significantly negative risk for estrogen receptor (ER)+/progesterone receptor (PR)+ postmenopausal breast cancer [both had a Ptrend=0.001; HR=0.80 (0.67-0.94) and HR=0.74 (0.64-0.86), respectively], for the largest body shapes compared with the first body shape. No significant association with body shape was found at the other ages. In terms of body shape evolution throughout life, women with a large body shape at menarche, irrespective of their body shape before or after menarche, tended to have a decreased risk for ER+/PR+ postmenopausal breast cancer compared with women who were constantly lean. Adjustment for current BMI or age at menarche did not modify any associations. Our study found an inverse association between adiposity at menarche and the risk for ER+/PR+ postmenopausal breast cancer, independent of corpulence at other ages. This work should encourage longitudinal studies with hormonal information to examine the underlying biological mechanisms.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2012; 22(1). DOI:10.1097/CEJ.0b013e328355ec04 · 2.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Early life body size and circulating levels of IGF-1 and IGFBP-3 have been linked to increased risks of breast and other cancers, but it is unclear whether these exposures act through a common mechanism. Previous studies have examined the role of IGF-1 and IGFBP-3 genetic variation in relation to adult height and body size, but few studies have examined associations with birthweight and childhood size. Methods We examined whether htSNPs in IGF-1 and the IGFBP-1/IGFBP-3 gene region are associated with the self-reported outcomes of birthweight, body fatness at ages 5 and 10, and body mass index (BMI) at age 18 among healthy women from the Nurses’ Health Study (NHS) and NHSII. We used ordinal logistic regression to model odds ratios (ORs) and 95% confidence intervals (CI) of a one category increase for birthweight and somatotypes at ages 5 and 10. We used linear regression to model associations with BMI at age 18. Results Among 4567 healthy women in NHS and NHSII, we observed no association between common IGF-1 or IGFBP-1/IGFBP-3 SNPs and birthweight, body fatness at ages 5 and 10, or BMI at age 18. Conclusions Common IGF-1 and IGFBP-1/IGFBP-3 SNPs are not associated with body size in early life.
    BMC Public Health 08/2012; 12(1):659. DOI:10.1186/1471-2458-12-659 · 2.32 Impact Factor