Objective: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGFbinding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. Design and methods: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre-and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. Results: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre-and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. Conclusions: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

OBJECTIVE -To investigate whether hyperglycemia is associated with increased cancer risk. RESEARCH DESIGN AND METHODS -In the VästerbottenIntervention Project of northern Sweden, fasting and postload plasma glucose concentrations were available for 33,293 women and 31,304 men and 2,478 incident cases of cancer were identified. Relative risk (RR) of cancer for levels of fasting and postload glucose was calculated with the use of Poisson models, with adjustment for age, year of recruitment, fasting time, and smoking status. Repeated measurements 10 years after baseline in almost 10,000 subjects were used to correct RRs for random error in glucose measurements.RESULTS -Total cancer risk in women increased with rising plasma levels of fasting and postload glucose, up to an RR for the top versus bottom quartile of 1.26 (95% CI 1.09 -1.47) (P trend Ͻ0.001) and 1.31 (1.12-1.52) (P trend ϭ 0.001), respectively. Correction for random error in glucose measurements increased these risks up to 1.75 (1.32-2.36) and 1.63 (1.26 -2.18), respectively. For men, corresponding uncorrected RR was 1.08 (0.92-1.27) (P trend ϭ 0.25) and 0.98 (0.83-1.16) (P trend ϭ 0.99), respectively. Risk of cancer of the pancreas, endometrium, urinary tract, and of malignant melanoma was statistically significantly associated with high fasting glucose with RRs of 2.49 (1.23-5.45) (P trend ϭ 0.006), 1.86 (1.09 -3.31) (P trend ϭ 0.02), 1.69 (0.95-3.16) (P trend ϭ 0.049), and 2.16 (1.14 -4.35) (P trend ϭ 0.01), respectively. Adjustment for BMI had no material effect on risk estimates.CONCLUSIONS -The association of hyperglycemia with total cancer risk in women and in women and men combined for several cancer sites, independently of obesity, provides further evidence for an association between abnormal glucose metabolism and cancer. Diabetes Care 30:561-567, 2007T ype 2 diabetes, an extreme state of glucose intolerance, is associated with elevated plasma levels of glucose and insulin, both before and after its diagnosis, and is associated with an increased risk of cancers of the liver, pancreas, colon, endometrium, kidney, and breast (1,2). Less is known, however, about the effect on cancer risk of moderately elevated glucose levels among nondiabetic subjects.Recently, total cancer risk was reported to be modestly increased in women and men with elevated levels of fasting glucose in a very large cohort study of 1.3 million Korean men and women with 53,833 incident cases of cancer (3). Five substantially smaller prospective studies (4 -8) with a total number of ϳ11,000 incident cases of cancer also have reported data on associations between fasting or postload glucose and cancer incidence or mortality. Here, we report the results from a prospective study in northern Sweden, with the aim to estimate the relationship of hyperglycemia, as measured by fasting and postload glucose, with the risk of cancer overall and the risk of cancer at specific organ sites. RESEARCH DESIGN AND METHODS The Northern Sweden Health and Disease CohortThe Västerbotten Interventio...

Purpose: Angiogenesis is a necessary step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a major mediator of breast cancer angiogenesis. Therefore, we investigated the association of polymorphisms in the VEGF gene with breast cancer risk and prognostic characteristics of the tumors in a large case-control study. Experimental Design: We examined three polymorphisms in the VEGF gene (−2578C/A, −1154G/A, and +936C/T) in 571 familial breast cancer cases from Poland and Germany and −2578C/A, −634G/C, and +936C/T polymorphisms in 974 unselected breast cancer cases from Sweden together with ethnically and geographically selected controls. Results: None of the polymorphisms or any haplotype was significantly associated with either familial or unselected breast cancers. Our study suggests that the +936C/T polymorphism is unlikely to be associated with breast cancer. We also analyzed the unselected cases for genotypes or haplotypes that associated with tumor characteristics. The −634CC genotype and the −2578/−634 CC haplotype were significantly associated with high tumor aggressiveness (large tumor size and high histologic grade, P < 0.01) and the −2578AA genotype and the −2578/−634 AG haplotype with low histologic grade tumors (P = 0.04). The genotypes and haplotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Conclusions: Although none of the polymorphisms studied in the VEGF gene was found to influence susceptibility to breast cancer significantly, some of the VEGF genotypes and haplotypes may influence tumor growth through an altered expression of VEGF and tumor angiogenesis.

In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age.

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