Background and aims The increase in breast cancer incidence over recent decades has been accompanied by an increase in the frequency of metabolic syndrome. Several studies suggest that breast cancer risk is associated with the components of metabolic syndrome (high serum glucose and triglycerides, low HDL-cholesterol, high blood pressure, and abdominal obesity), but no prospective study has investigated risk in relation to the presence of explicitly defined metabolic syndrome. We investigated associations between metabolic syndrome, its components, and breast cancer risk in a nested case-control study on postmenopausal women of the ORDET cohort. Methods and results After a median follow-up of 13.5 years, 163 women developed breast cancer; metabolic syndrome was present in 29.8%. Four matched controls per case were selected by incidence density sampling, and rate ratios were estimated by conditional logistic regression. Metabolic syndrome (i.e. presence of three or more metabolic syndrome components) was significantly associated with breast cancer risk (rate ratio 1.58 [95% confidence interval 1.07–2.33]), with a significant risk increase for increasing number of components (P for trend 0.004). Among individual metabolic syndrome components, only low serum HDL-cholesterol and high triglycerides were significantly associated with increased risk. Conclusions This prospective study indicates that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women. Although serum HDL-cholesterol and triglycerides had the strongest association with breast cancer, all components may contribute to increased risk by multiple interacting mechanisms. Prevention or reversal of metabolic syndrome by life-style changes may be effective in preventing breast cancer in postmenopausal women.

Background: Endogenous sex hormone levels have been associated with increased breast cancer risk in postmenopausal women in several prospective studies. However, it remains unclear to what extent serum hormone-breast cancer associations differ with receptor status. Methods: Associations between serum sex hormone levels and breast cancer risk were assessed in a nested case-control study on postmenopausal women of the ORDET cohort. After a median follow-up of 13.5 years, 165 women developed breast cancer. Relative risks of developing breast cancer were estimated by conditional logistic regression. Results: Total and free testosterone levels were directly associated with breast cancer risk [relative risk, 3.28 (95% confidence interval, 1.93-5.55) and 2.86 (95% confidence interval, 1.66-4.94), respectively, for highest versus lowest quartile]. When relations between hormone level and risk of breast cancer expressing various receptor combinations were assessed, high total testos-

High circulating glucose, insulin resistance and obesity appear to be associated with increased risk of breast cancer (BC). We sought further insight into the relation of these variables to BC. We assessed associations of BC risk with serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) index and sex-binding hormone globulin (SHBG) in women recruited to the ORDET cohort who gave blood samples in [1987][1988][1989][1990][1991][1992]. After a median 13.5 years of follow-up, 356 women developed BC. Four matched controls per case were selected by incidence density sampling, and rate ratios (RR) were estimated by conditional logistic regression. Women in the highest glucose quartile had a significantly greater risk of BC than those in the lowest glucose quartile (RR 1.63; 95% CI: 1.14-2.32; p for trend of 0.003). The association was significant in pre and post menopausal women separately and in women diagnosed after 55 years. Women in the highest HOMA-IR quartile had higher BC risk than the lowest quartile (RR 1.44; 95% CI: 1.03-2.02). Significantly increased BC risk in women diagnosed after 55 years was also present in the highest HOMA-IR quartile; in the same group decreased BC risk was significantly associated with high SHBG. The results of this study add to the existing epidemiological evidence that hyperglycemia and insulin resistance increase BC risk.Hypoxia is widespread in solid tumors 1 selecting tumor cells adapted to hypoxic conditions. Anaerobic use of glucose through enhanced glycolysis is one adaptation to hypoxia present in most solid tumors. 2 Most solid tumors also have high rates of glucose uptake, 3 and recent molecular studies show that several of the multiple genetic alterations causing cancer development directly affect glycolysis and the cellular response to hypoxia. 3 These findings add weight to the hypothesis that hyperglycemia and hyperinsulinemia (consequence of insulin resistance) play a role in cancer growth. 3,4 Hyperglycemia and hyperinsulinemia result from dysregulation of insulin secretion, and of insulin action at the cellular level. 5 Elevated insulin may also play a role in cancer promotion, particularly breast cancer (BC), by up-regulating ovarian steroid secretion and other growth factors such as IGF-1. 6,7 Prospective studies addressing the relationship between BC and prediagnostic levels of glucose have yielded conflicting results. Stattin et al. 8 found that fasting glucose was significantly associated with BC risk in women below 49 years, whereas Rapp et al. 9 and Bjørge et al. 10 found significantly increased risk only among elderly women. Our previous study on the ORDET cohort found that high fasting glucose was related to BC risk, but the association was significant only in premenopausal women. 11 Other cohort studies found no significant association between serum glucose levels and BC. [12][13][14][15] As regards the roles of insulin and C-peptide, a metaanalysis of epidemiological studies 16 published in 2008 reported that although...

The effects of transportation and delay in processing of blood samples on the concentration of biomarkers are significant in epidemiological studies for which specimens are collected from participants at locations other than a designated center or laboratory. These sources of variability in measurement were studied by collecting two sets of blood samples from 51 men between 26 and 50 years of age. The first set was sent immediately to the laboratory for processing. The second set was transported by car for one hour and then returned to the laboratory for processing. Both sets were stored together at -80 degrees C until the end of the study. Several blood constituents were evaluated. Vitamins, liver enzymes, and electrolytes showed no changes in concentration after transport by car for one hour. There were decreases in the concentrations of red and white blood cells, high-density-lipoprotein cholesterol, glucose, and creatinine after transportation. The transported total cholesterol, total testosterone, free testosterone, alkaline phosphatase, total bilirubin, and thiobarbituric acid-reactive substances increased in concentration. Although transportation and delay in processing of blood samples do not appear to greatly impact relative risk estimates, epidemiologists should be aware of these potential sources of variability in measurement and consider the consequences in their particular study.