Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
International Journal of Cancer (Impact Factor: 5.09). 12/2009; 125(11):2704-10. DOI: 10.1002/ijc.24609
Source: PubMed


Experimental and epidemiological evidence suggests that circulating glucose and insulin may play a role in breast carcinogenesis. However, few cohort studies have examined breast cancer risk in association with glucose and insulin levels, and studies to date have had only baseline measurements of exposure. We conducted a longitudinal study of postmenopausal breast cancer risk using the 6% random sample of women in the Women's Health Initiative clinical trials whose fasting blood samples, provided at baseline and at years 1, 3 and 6, were analyzed for glucose and insulin. In addition, a 1% sample of women in the observational study, who had glucose and insulin measured in fasting blood samples drawn at baseline and in year 3, were included in the analysis. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of baseline and follow-up measurements of serum glucose and insulin with breast cancer risk. All statistical tests were 2-sided. Among 5,450 women with baseline serum glucose and insulin values, 190 incident cases of breast cancer were ascertained over a median of 8.0 years of follow-up. The highest tertile of baseline insulin, relative to the lowest, was associated with a 2-fold increase in risk in the total population (multivariable hazard ratio 2.22, 95% confidence interval 1.39-3.53) and with a 3-fold increase in risk in women who were not enrolled in the intervention arm of any clinical trial (multivariable hazard ratio 3.15, 95% confidence interval 1.61-6.17). Glucose levels showed no association with risk. Analysis of the repeated measurements supported the results of the baseline analysis. These data suggest that elevated serum insulin levels may be a risk factor for postmenopausal breast cancer.

Download full-text


Available from: Geoffrey C Kabat, Nov 21, 2014
  • Source
    • "Another recent study (Anand et al., 2014) has found raised chromosomal abnormalities in diabetic subjects as compared to healthy controls, thus increasing he risk of cancer may be due to genomic instability. Conflicting results have been achieved by studies (Manjer et al., 2001; Muti et al., 2002; Mink et al, 2002; Stattin et al., 2007; Kabat et al., 2009) that have attempted to determine the relationship of increased FBG with cancer. To our knowledge no similar study has been conducted in this region to establish elevated FBG as a risk factor for breast cancer. "

    Full-text · Article · Feb 2015 · Asian Pacific journal of cancer prevention: APJCP
  • Source
    • "The stimulation of cell proliferation is an unfavorable insulin effect in cancer cells. Hyperinsulinemia, both endogenous and exogenous, is considered a factor that may increase cancer risk and cancer progression in diabetic and obese patients (Vigneri et al., 2006; Pisani, 2008; Kabat et al., 2009; LeRoith, 2010; Janghorbani et al., 2012; Karlstad et al., 2013; Sciacca et al., 2013). However, different cancers can behave differently. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperinsulinemia is a likely cause of the increased cancer incidence and mortality in diabetic patients, but its role is difficult to define in vivo. Previous in vitro studies testing the mitogenic potential of insulin and its analogs provided incomplete and sometimes contradictory results. To better evaluate cancer cell responsiveness to insulin, to its analogs and to IGF-I, we measured under identical experimental conditions cell proliferation, invasiveness, and foci formation in six cancer cell lines with different insulin receptor family expression levels. The cancer cells studied have a different expression of insulin receptor (IR), its isoforms (IR-A and IR-B), and of the IGF-I receptor. The data indicate that insulin stimulates proliferation in all cancer cell lines, invasiveness in some, and foci formation in none. Cancer cell responses to insulin (and IGF-I) are not related to receptor expression levels; moreover, hormone-stimulated proliferation and invasiveness are not correlated. IGF-I is a more potent stimulator than insulin in most but not all cancer cell lines. Insulin analogs including M1 and M2 Glargine metabolites stimulate cancer cells similar to insulin. However, exceptions occur for specific analogs in particular cancer cells. In conclusion, in vitro insulin is an effective growth factor for all cancer cells but the biological response to insulin cannot be predicted on the basis of receptor expression levels. In the clinical setting, these observations should be taken in account when deciding treatment for diabetic patients who are at risk of undiscovered cancer or survivors of oncological diseases. J. Cell. Physiol. 9999: XX–XX, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2014 · Journal of Cellular Physiology
  • Source
    • "Table 1 summarizes the main characteristics of the included studies. Of the 22 studies included, 20 were case-control [11], [12], [13], [14], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35] and 2 cross-sectional studies [36], [37]. Breast cancer cases were identified by pathology/medical records in 12 studies and cancer/tumor registries in 7 studies; no information was provided in 3 studies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women. Study Design We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models. Results Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD −0.03, 95%CI −0.32 to 0.27; p = 0.9). Similarly, non-fasting/fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, −0.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMA-IR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p<0.00001). Conclusions Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.
    Full-text · Article · Jun 2014 · PLoS ONE
Show more