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Michael N Pollak

Publications and source records attributed to Michael N Pollak.

At least 19 recordsLinked to original sources
PubMed2007

Circulating insulin and c-peptide levels and risk of breast cancer among predominately premenopausal women.

Insulin and insulin resistance have been hypothesized to increase the risk of breast cancer as insulin increases breast cell proliferation and inhibits sex hormone binding globulin. Although insulin is directly related to body weight, adiposity is inversely associated with breast cancer risk in premenopausal women but directly related to risk in postmenopausal women. To explore the association between insulin and c-peptide levels and breast cancer risk, we conducted a nested case-control study of predominantly premenopausal women within the Nurses' Health Study II cohort. From 1996 to 1999, blood samples were collected from 29,611 participants. A total of 317 cases were diagnosed after blood collection and before June 2003 and matched to 634 controls; 75% of these women were premenopausal at blood collection. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RR) and 95% confidence intervals (95% CI). Among women with fasting blood samples (n = 211 cases), insulin was suggestively inversely associated with breast cancer risk (highest versus lowest quartile: RR, 0.5; 95% CI, 0.3-1.0; P(trend) = 0.06). Among all women, c-peptide was not associated with breast cancer risk (highest versus lowest quartile: RR, 1.1; 95% CI, 0.7-1.7; P(trend) = 0.79); results were similar among fasting samples. These associations did not differ by age, body mass index, or waist-to-hip ratio. Overall, higher levels of insulin and c-peptide were not associated with a higher risk of breast cancer among predominantly premenopausal women.

Adult↗
PubMed2006

Diabetes mellitus and cancer risk in a population-based case-control study among men from Montreal, Canada.

Diabetics may have a higher risk of cancer, notably liver and pancreatic cancers. Evidence about other cancer types remains sparse. The authors examined potential associations between diabetes and several types of cancer in a large multicancer case-control project carried out in Montreal, Canada, in the 1980s. This report, based on 3,107 male cancer cases and 509 population controls, uses information on diabetes and several covariates collected by interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the associations between diabetes and each of 12 cancer types. Risks of pancreatic and liver cancers were increased among diabetics: adjusted ORs were 2.1 (95% CI: 1.0, 4.3) for pancreatic and 3.1 (95% CI: 1.1, 8.8) for liver cancer. The increased risk of pancreatic cancer was completely restricted to those with recent onset of diabetes; this was likely a manifestation of reverse causality. Conversely, the increased risk of liver cancer was independent of the interval between diabetes and cancer diagnoses. No associations were observed with melanoma, non-Hodgkin's lymphoma, cancers of the esophagus, stomach, colon, rectum, lung, prostate, bladder and kidney. In conclusion, diabetes was associated with an increased risk of liver cancer among men, but with no other cancer type including pancreatic cancer.

Adult↗
PubMed2006

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3).

BACKGROUND: An increasing number of epidemiologic studies are investigating the relationship between serum levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) and risk of cancer, cardiovascular disease, and other diseases. However, little is known regarding the effects of blood specimen processing time on measured levels of total and free IGF-I, and on IGFBP-3, the major binding protein. DESIGN: Two serum separation tubes were collected from each of 12 subjects. One tube was centrifuged as soon as possible following blood collection (a mean of 47 min; range=30-80 min), and serum aliquots were placed into -70 degrees C storage either shortly after centrifugation, or following 2, 4, 10, or 24 h at ambient temperature (measured from the time of blood draw). The second serum separation tube was maintained at ambient temperature for 24h before centrifugation and freezing. Total IGF-I, free IGF-I, and IGFBP-3 levels were determined using commercial enzyme linked immunosorbent assays (ELISAs) commonly employed in epidemiologic studies. The effects of time until centrifugation and freezing on seroassay results were evaluated using generalized estimating equation (GEE) linear regression models and Spearman correlation. RESULTS: Total IGF-I and IGFBP-3 levels did not vary significantly with the amount of time at ambient temperature following centrifugation, even up to 24 h, in blood specimens that were centrifuged soon after collection (all pchi2). However, free IGF-I levels increased significantly with increasing time intervals between centrifugation and freezing in these same specimens (ptrend <0.001). Total IGF-I/IGFBP-3 molar ratio, a crude measure of free IGF-I levels, showed no clear association. In blood specimens that were not centrifuged for 24h, total IGF-I, free IGF-I, and IGFBP-3 were each significantly elevated (each pchi2) compared with results in blood specimens that were centrifuged and frozen soon after collection, whereas the total IGF-I/IGFBP-3 molar ratio was decreased pchi2. Nonetheless, all total IGF-I, free IGF-I, IGFBP-3, and total IGF-I/IGBFBP-3 molar ratio values altered by delays in processing were highly correlated with the values in specimens processed as soon as possible (all Spearman rank correlation coefficients 0.84). CONCLUSIONS: Total IGF-I and IGFBP-3 can be fairly stably measured in serum with commonly used commercial assays regardless of the interval between blood collection and freezing, up to at least 24 h, as long as centrifugation and serum aliquoting take place shortly after blood collection. Free IGF-I levels, however, increase steadily with the time interval until freezing, even if serum separation has been completed soon after blood collection. Because the altered serum values are highly correlated with the referent values, analysis of total IGF-I, free IGF-I, IGFBP-3, and total IGF-I/IGFBP-3 molar ratio data by quartile might help mitigate concerns regarding the effects of delays in processing time.

Adult↗
PubMed2006

C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, and the risk of distal colorectal adenoma in women.

BACKGROUND: Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer. METHODS: We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases and controls were individually matched on year of birth, time period of and indication(s) for endoscopy, and date of blood draw. RESULTS: High concentrations of C-peptide, an indicator of insulin secretion, were statistically significantly associated with risk of distal colorectal adenoma [multivariable relative risk (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01-2.66; P = 0.01], even after including body mass index and physical activity in the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did not show any clear association with risk for adenoma (MVRR top versus bottom quartile, 1.08; 95% CI, 0.56-2.07). These associations did not differ significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was associated with a nonstatistically significant increased risk of colorectal adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44). CONCLUSIONS: High HbA1c and low IGFBP-1 were not clearly associated with increased risk of distal colorectal adenoma. However, our current results and previous associations between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a role throughout the development of colorectal neoplasia.

Adenoma↗
PubMed2006

Reproducibility of plasma steroid hormones, prolactin, and insulin-like growth factor levels among premenopausal women over a 2- to 3-year period.

Few studies have evaluated whether a single blood hormone measurement, as is available in most epidemiologic studies, sufficiently characterizes a premenopausal woman's long-term hormone levels; there is particular concern whether sex steroid hormones, which fluctuate during the menstrual cycle, are reliable. We conducted a prospective study within the Nurses' Health Study II to examine the reproducibility of plasma estrogens, androgens, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3). One blood sample per year over 3 years was collected from 113 premenopausal women during both the follicular and luteal phases of the menstrual cycle. We calculated intraclass correlation coefficients (ICC) across the three samples for all women. Among estrogens, ICCs ranged from 0.38 (estradiol) to 0.60 (estrone sulfate) in the follicular phase and from 0.44 (estrone) to 0.69 (estrone sulfate) in the luteal phase. Among androgens, ICCs ranged from 0.58 (androstenedione) to 0.94 [dehydroepiandrostenedione sulfate (DHEAS)] in the follicular phase and from 0.56 (testosterone) to 0.81 (DHEAS) in the luteal phase. When values were averaged across the follicular and luteal phases, the ICC for prolactin was 0.64 whereas ICCs for IGF-I and IGFBP-3 were 0.86 and 0.82, respectively. The ICC for progesterone in the luteal phase was only 0.29. These data suggest that for androgens, estrone sulfate, prolactin, IGF-I, and IGFBP-3, a single measurement can reliably categorize average levels over at least a 3-year period in premenopausal women. For estrone and estradiol, where ICCs were relatively low, it is important to use reproducibility data such as those to correct for measurement error in epidemiologic studies.

Adult↗
PubMed2006

Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial.

Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency may be due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes.

Adenocarcinoma↗
PubMed2006

Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II.

Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses' Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69-1.39; IGFBP-1, 0.95, 95% CI, 0.63-1.41; IGFBP-3, 1.10, 95% CI, 0.78-1.54; GH, 1.09, 95% CI, 0.82-1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.

Adult↗
PubMed2005

Plasma IGF-I levels and cognitive performance in older women.

BACKGROUND: Emerging biologic and epidemiologic evidence suggests benefits of insulin-like growth factor-I (IGF-I) in cognitive aging. OBJECTIVE: To examine the relation of circulating IGF-I to cognition. METHODS: We measured plasma IGF-I and IGF-binding protein-3 (IGFBP-3) in 590 women aged 60-68 years. An average 10 years later, we administered telephone-based tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, category fluency, and attention. We estimated multivariable-adjusted mean differences in performance across levels of IGF-I/IGFBP-3 molar ratio. RESULTS: On the TICS, each standard deviation (S.D.) increase in molar ratio was significantly associated with better performance: multivariable-adjusted mean difference=0.2 units, 95% confidence interval (0.0,0.4), p=0.05. This effect estimate for each S.D. increase in molar ratio was cognitively equivalent to the mean difference we observed on the TICS between women 1 year apart in age. On a global score combining all tests, there was also a trend of better performance with each S.D. increase in molar ratio (p=0.07). IGF-I levels were not associated with performance in verbal memory. CONCLUSIONS: Higher IGF-I levels may be associated with better general cognition.

Aged↗
PubMed2005

Insulin-like growth factor receptor I targeting in epithelial ovarian cancer.

OBJECTIVES: Preclinical evaluation of the anti-neoplastic activity of an insulin-like growth factor I receptor (IGF-IR) kinase inhibitor in ovarian cancer. METHODS: The OVCAR-3 and OVCAR-4 cell lines were investigated under serum-free tissue culture conditions. IGF-I and IGF-II production were evaluated by standard ELISA and immunohistochemistry. IGF-IR expression and protein levels were evaluated by Western blotting. Cytotoxicity assays were performed in triplicates using the Alamar colorimetric assay. Apoptosis was evaluated by flow cytometry and by Western blotting for PARP. RESULTS: The OVCAR-3 and OVCAR-4 cell lines produce IGF-I and IGF-II, and express IGF-IR, detectable by Western blotting, supporting the existence of an autocrine loop. The existence of this loop justified studies of NVP-AEW541, a small molecular weight inhibitor of the IGF-IR kinase. We observed growth inhibition of the ovarian cancer cell lines, with IC50 between 5 and 15 microM. We also observed that NVP-AEW541 sensitized cells to cisplatin in vitro. Western blotting demonstrated that NVP-AEW541 induced apoptosis at the concentrations that were used in the cytotoxicity assays, and decreased the concentration of the phosphorylated AKT signaling protein downstream of the IGF-IR. CONCLUSIONS: IGF-IR is a potential new molecular target in ovarian cancer. The anti-neoplastic activity of NVP-AEW541 in ovarian cancer was observed at concentrations higher than those previously reported for multiple myeloma, suggesting the possibility that a portion of the observed anti-neoplastic activity could involve targets other than the IGF-IR. Experiments are being conducted to investigate the cytotoxicity profile in vivo and the clinical relevance of NVP-AEW541 in ovarian cancer treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era.

OBJECTIVE: The insulin-like growth factor (IGF) axis is thought to contribute to the growth and progression of prostate cancer. Some prospective studies support a direct association between IGF-1 and prostate cancer, in particular advanced disease, whereas both inverse and direct associations with prostate cancer have been reported for insulin-like growth factor binding protein-3 (IGFBP-3), the major IGF-1 binding protein in circulation. We prospectively investigated the associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer detected in the PSA era. METHODS: We identified 462 prostate cancer cases diagnosed after providing a blood specimen in 1993, but before January 1998 among men in the Health Professionals Follow-up Study. Controls were 462 age-matched men without prostate cancer who had had a PSA test after providing a blood specimen. We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer. RESULTS: Men with higher concentrations of IGF-1 (comparing extreme quartiles OR=1.37, 95% CI 0.92-2.03, p-trend=0.05) and IGFBP-3 (OR=1.62, 95% CI 1.07-2.46, p-trend=0.08) had a higher risk of prostate cancer. After mutual statistical adjustment, these associations were attenuated for both IGF-1 (OR=1.17, 95% CI 0.69-1.99, p-trend=0.29) and IGFBP-3 (OR=1.40, 95% CI 0.80-2.44, p-trend=0.56). We found no significant association of IGF-1 with regionally invasive or metastatic (>/=T3b, N1, or M1) prostate cancer, although the number of these cases was small (n=42). CONCLUSIONS: Our findings for IGF-1 and prostate cancer diagnosed in the PSA era are similar to most previous studies, albeit weaker in magnitude. Our suggestive positive findings for IGFBP-3 are similar to some studies, but in direct contrast to others.

Aged↗
PubMed2005

Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk.

BACKGROUND: Earlier data support the hypothesis that the relation between circulating insulin-like growth factor-I (IGF-I) levels and breast cancer risk differs by menopausal status. The strong association of IGF-I with height in childhood and weak or no association between adult levels and adult height also suggest that IGF levels in young women may better reflect an exposure time period of importance to breast cancer. Few studies have assessed IGF binding protein-1 (IGFBP-1) or free IGF and breast cancer risk. MATERIALS AND METHODS: We conducted a large case-control study nested within the prospective Nurses' Health Study. Plasma concentrations of IGF-I, free IGF, IGFBP-3, and IGFBP-1 were measured in blood samples collected in 1989 to 1990. Eight hundred women were identified who had a diagnosis of invasive or in situ breast cancer after blood collection, up to 1998, 27% of whom were premenopausal at blood collection. To those 800 women, one to two controls were age-matched for a total of 1,129 controls. We used logistic regression models to estimate the relative risk (RR) of breast cancer associated with IGF levels. FINDINGS: Among postmenopausal women, neither IGF-I, IGFBP-3, IGFBP-1, nor free IGF was associated with breast cancer risk [RRs, top versus bottom quintile: IGF-I, 1.0; 95% confidence interval (95% CI), 0.7-1.4; IGFBP-3, 0.8; 95% CI, 0.6-1.1; IGFBP-1, 0.9; 95% CI, 0.6-1.5; and free IGF, 1.0; 95% CI, 0.6-1.4]. Among premenopausal women, IGFBP-3, IGFBP-1, and free IGF similarly were not associated with breast cancer risk (RRs, top versus bottom quintile: IGFBP-3, 1.2; 95% CI, 0.8-2.3; IGFBP-1, 1.5; 95% CI, 0.8-3.0; and free IGF, 1.1; 95% CI, 0.7-2.1). Higher IGF-I plasma levels, however, were associated with a modestly elevated breast cancer risk (RR, 1.6; 95% CI, 1.0-2.6) among the premenopausal women, with a stronger association among premenopausal women ages < or =50 (RR, 2.5; 95% CI, 1.4-4.3); further adjustment for IGFBP-3 did not greatly change these estimates. INTERPRETATION: Circulating IGF-I levels seem to be modestly associated with breast cancer risk among premenopausal women, but not among postmenopausal women. IGFBP-3, IGFBP-1, and free IGF are not associated with breast cancer risk in either premenopausal or postmenopausal women in this cohort.

Adult↗
PubMed2005

Centralized blood processing for the selenium and vitamin E cancer prevention trial: effects of delayed processing on carotenoids, tocopherols, insulin-like growth factor-I, insulin-like growth factor binding protein 3, steroid hormones, and lymphocyte viability.

This experiment examined the effects of delays in separation and freezing of whole blood components on analytes of interest in studies of prostate cancer prevention, in order to evaluate the feasibility of centralized processing of blood for the multisite Selenium and Vitamin E Cancer Prevention Trial. Blood from 40 healthy men was subjected to four treatment protocols, allowing the contrast of immediate processing to delays of 32, 72, and 144 hours. At 32 hours, simulating refrigerated storage and overnight shipping, there was a 2.9% decrease (95% confidence interval, 0.7-5.1) in insulin-like growth factor-I (IGF-I) but no significant change in carotenoids, tocopherols, testosterone, 3alpha-androstanediol glucuronide (AAG), sex hormone-binding globulin (SHBG) or insulin-like growth factor binding protein 3 (IGFBP3). A 144-hour processing delay, simulating weekend blood collection or shipping delay, resulted in significant changes in gamma-tocopherol (-1.5%), IGF-I (-5.7%), IGFBP3 (-2.9%), SHBG (-4.0%), testosterone (+4.7%), and AAG (+5.5%). The rank-order and intraclass correlations between analytes from blood processed immediately and those subjected to delayed processing were 0.96 or higher for carotenoids, tocopherols, AAG, and SHBG, and between 0.87 and 0.95 for IGF-I, IGFBP3, and testosterone. A 32-hour delay decreased lymphocyte viability from 82.5% to 75.0% (P = 0.45), but a 72-hour delay decreased viability to 36.8% (P < 0.001). Overnight shipping and centralized processing is an acceptable approach to blood collection in large multisite trials examining the cancer-related measures proposed in the Selenium and Vitamin E Cancer Prevention Trial. Longer processing delays, however, have small but statistically significant effects on many analytes and substantially decrease lymphocyte viability.

Adult↗
PubMed2005

A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women.

Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-I have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-I to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention.

Adult↗
PubMed2005

Racial differences in premenopausal endogenous hormones.

Differences in breast cancer incidence across racial groups are well documented. African Americans have the highest rates of premenopausal breast cancer and Asians have lower breast cancer rates across all age groups. We hypothesized that levels of premenopausal endogenous hormones and growth factors, risk factors that have been predictive of breast cancer, would differ by race. Using a cross-sectional study design, we tested this hypothesis in the Nurses' Health Study II. We assayed estradiol, progesterone, prolactin, sex hormone binding globulin (SHBG), insulin-like growth factor-I (IGF-I), and IGFBP-3 in 111 African American and 111 Asian American women, matched to 111 Caucasian women on age, day of luteal phase, and day, time, and fasting status at blood collection. We analyzed the association between race and hormone levels using robust linear regression methods. In multivariate models, compared with Caucasians, African Americans had 18% higher levels of estradiol (P < 0.01), 17% higher free estradiol (P < 0.01), 11% lower SHBG (P = 0.05), 11% higher IGF-I (P < 0.01), 25% higher free IGF-I (P < 0.01), and 9% lower IGFBP-3 (P < 0.01) levels. In multivariate models, compared with Caucasian women, Asian Americans had 22% higher calculated free estradiol (P < 0.01), 31% lower SHBG (P < 0.01), and 25% higher free IGF-I (P < 0.01) levels. No racial differences were found in progesterone and prolactin levels. Our study showed hormone differences consistent with breast cancer risk between Caucasians and African Americans but inconsistent with breast cancer risk between Asian Americans and Caucasians. Further research is needed to explore differences across racial groups and the link between endogenous hormones and breast cancer risk.

Adult↗
PubMed2004

Insulin-like growth factors and neoplasia.

Prospective studies suggest that individuals with circulating levels of insulin-like growth factor 1 (IGF-1) at the high end of the normal range are at increased risk for several common cancers. Further data implicate IGF-1 and hyperinsulinism as candidate mediators of the effects of body size on cancer risk and prognosis. Ongoing research seeks to confirm these findings, to clarify the underlying physiology, and to assess their relevance to patterns of cancer incidence. In vivo models have not only provided data consistent with the epidemiological observations, but also suggest that IGF-1 signalling stimulates growth of established cancers. This has led to the development of novel IGF-I receptor targeting therapies which have impressive antineoplastic activity in experimental systems.

Animals↗
PubMed2003

Polymorphic variation at the -202 locus in IGFBP3: Influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk.

Previous reports have suggested an association between circulating IGFBP-3 levels and the risk of premenopausal breast cancer, and a single nucleotide polymorphism (SNP) in the promoter region of IGFBP-3 (nucleotide -202) was shown to influence transcription. There is prior evidence that the action of antiproliferative agents such as retinoids and selective estrogen receptor modulators (SERMs) act in part by upregulating IGFBP3 gene expression. We identified 677 women with incident breast cancer and 834 matched controls from the Nurses' Health Study (NHS) and genotyped them at the -202 locus. For 943 of these women, we had previously measured IGF-I and IGFBP-3 plasma levels, and for 861 of these subjects, plasma retinol levels were available. Age-adjusted mean circulating IGFBP-3 levels were highest in the individuals with the AA genotype and decreased significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4,426 ng/ml, 4,060 ng/ml and 3,697 ng/ml, respectively). We found a positive relation between age-adjusted IGFBP-3 levels and plasma retinol (14% difference in IGFBP-3 in top vs. bottom tertiles of retinol, p for trend < 0.001; Spearman correlation coefficient r = 0.25), which was similar across genotypes at the -202 IGFBP3 locus (interaction term, F = 0.10, p = 0.91). Breast cancer risk was not significantly related to genotype at the -202 locus in our prospective analyses. We confirmed a relation between the -202 IGFBP3 polymorphism and IGFBP-3 serum levels and observed a positive correlation between circulating retinol levels and circulating IGFBP-3 levels, providing further evidence that retinoids may influence IGF physiology. Our data do not demonstrate a significant influence of this locus on breast cancer risk, but we cannot exclude a minor influence or an influence confined to subgroups.

Adult↗