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The National Center for Advancing Translational Science (NCATS) seeks to improve upon the translational process to advance research and treatment across all diseases and conditions and bring these interventions to all who need them. Addressing the racial/ethnic health disparities and health inequities that persist in screening, diagnosis, treatment, and health outcomes (e.g., morbidity, mortality) is central to NCATS’ mission to deliver more interventions to all people more quickly. Working toward this goal will require enhancing diversity, equity, inclusion, and accessibility (DEIA) in the translational workforce and in research conducted across the translational continuum, to support health equity. This paper discusses how aspects of DEIA are integral to the mission of translational science (TS). It describes recent NIH and NCATS efforts to advance DEIA in the TS workforce and in the research we support. Additionally, NCATS is developing approaches to apply a lens of DEIA in its activities and research – with relevance to the activities of the TS community – and will elucidate these approaches through related examples of NCATS-led, partnered, and supported activities, working toward the Center’s goal of bringing more treatments to all people more quickly.

The internal research program of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health aims to fundamentally transform the preclinical translational research process to get more treatments to more people more quickly. The program develops and implements innovative scientific and operational approaches that accelerate and enhance translation across many diverse projects. Cross-disciplinary team science is a defining feature of our organization, with scientists at all levels engaged in multiple research teams. Here, we share our systems approach to nurturing cross-disciplinary team science, which leverages organizational policies, structures, and processes. Policies including the organizational mission statement, principles for ethical conduct of research, performance review criteria, and training program objectives and approaches reinforce the value of team science to achieve the program’s scientific goals. Structures including an organizational structure designed around solving translational problems, co-location of employees in a single state-of-the-art scientific facility, and shared-use laboratories, expertise and instrumentation facilitate collaboration. Processes including fluid team assembly, specialized project management, cross-agency partnerships, and decision making based on clear screening criteria and milestones enable effective team assembly and functioning. We share evidence of the impact of these approaches on the science and commercialization of findings and discuss pathways to broad adoption of similar approaches.

The National Center for Advancing Translational Sciences (NCATS) defines translational science as "the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process." A major goal of translational science is to determine commonalities across projects to identify principles for addressing persistent bottlenecks in this process. To meet this goal, translational scientists must be conversant in multiple disciplines, work in teams, and understand the larger translational science ecosystem. The development of these skills through translational science training opportunities, such as the translational science training offered by the NCATS intramural research program, prepares fellows for a variety of career options. The unique structure of the NCATS intramural program and the career outcomes of its alumni are described herein to demonstrate the distinct features of this training environment, the productivity of fellows during their time in training, and how this prepares fellows to be competitive for a variety of science careers. To date, the NCATS intramural research program has trained 213 people, ranging from high school to postdoctoral levels. These alumni have transitioned into a wide array of career functions, types, and sectors.

This study was conducted in 2016–2017 to better understand formal and informal leadership roles and activities of alumni from postdoctoral research training programs in cancer prevention. Data were obtained from surveys of 254 employed scientists who completed cancer prevention postdoctoral training within the National Cancer Institute (NCI) Cancer Prevention Fellowship Program, or at US research institutions through NCI-sponsored National Research Service Award (NRSA) individual postdoctoral fellowship (F32) grants, from 1987 to 2011. Fifteen questions categorized under Organizational Leadership, Research Leadership, Professional Society/Conference Leadership, and Broader Scientific/Health Community Leadership domains were analyzed. About 75% of respondents had at least one organizational leadership role or activity during their careers, and 13–34% reported some type of research, professional society/conference, or broader scientific/health community leadership within the past 5 years. Characteristics independently associated with leadership from regression models were being in earlier postdoctoral cohorts (8 items, range for statistically significant ORs = 2.8 to 10.8) and employment sector (8 items, range for statistically significant ORs = 0.4 to 11.7). Scientists whose race/ethnicity was other than white were less likely to report organizational leadership or management responsibilities (OR = 0.4, 95% CI 0.2–0.9). Here, many alumni from NCI-supported cancer prevention postdoctoral programs were involved in leadership, with postdoctoral cohort and employment sector being the factors most often associated with leadership roles and activities. Currently, there is relatively little research on leadership roles of biomedical scientists in general, or in cancer prevention specifically. This study begins to address this gap and provide a basis for more extensive studies of leadership roles and training of scientists.

The field of cancer prevention incorporates research all along the spectrum from basic science studies at the laboratory bench to epidemiology, behavioral sciences, and clinical studies, with the convergence of evidence from these different approaches aimed at implementing public health interventions that reduce the burden of this disease. Due to the necessity of multiple disciplines interacting in order to achieve a public health outcome, traditional discipline-specific training may not be adequately preparing the cancer prevention research workforce. We propose that cancer prevention researchers establish defined professional competencies which will allow them to shape the future directions of the field as well as to collaborate effectively in multidisciplinary teams, disseminate new findings beyond their own scientific circles, and advocate for their implementation for the public good. We previously proposed that these core competencies focus on knowledge of issues in other research fields, interdisciplinary communication, and leadership/teamwork. Here, we describe the reorganization of an existing course to incorporate activities deliberately designed to foster these competencies. We provide details about the course structure, student feedback, and ideas for future versions of this course. We hope this framework will be useful to others who are engaged in the collective effort to develop leaders in the field of cancer prevention research.

Introduction: The National Cancer Institute Principles and Practice of Cancer Prevention and Control course is a 4-week course encompassing a variety of cancer prevention and control topics that is open to attendees from medical, academic, government, and related institutions around the world. Themes related to the challenges health disparities present to cancer prevention efforts and potential solutions to these issues emerged from facilitated group discussions among the 2012 course participants. Materials and Methods: Small-group discussion sessions with participants (n 85 from 33 different countries) and facilitators (n 9) were held once per week throughout the 4-week course. Facilitators prepared open-ended questions related to course topics. Participants provided responses reflecting their opinions of topics on the basis of experiences in their countries. A thematic analysis was conducted to explore themes emerging from the discussion groups. Results: The varied influences of health disparities on cancer prevention efforts among 30 countries represented prominent themes across discussion groups. Participants discussed the interplay of individual characteristics, including knowledge and culture, interpersonal relationships such as family structure and gender roles, community and organizational factors such as unequal access to health care and access to treatment, and national-level factors including policy and government structure. Conclusion: The ideas and solutions presented here are from a geographically and professionally diverse group of individuals. The collective discussion highlighted the pervasiveness of health disparities across all areas represented by course participants and suggested that disparities are the largest impediment to achieving cancer prevention goals.

Studies examining career satisfaction of biomedical scientists are limited, especially in the context of prior postdoctoral training. Here we focused on career satisfaction defined as satisfaction with one's career trajectory and perceived salary competitiveness among a predominantly Ph.D.-trained population of scientists who completed cancer prevention-related postdoctoral training between 1987-2011. National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP) alumni (n = 114), and previous recipients of NCI-sponsored Ruth L. Kirschstein National Research Service Award (NRSA/F32) postdoctoral fellowships (n = 140) completed online surveys. Associations of career satisfaction and perception of salary competitiveness with demographic, training, and employment-related factors were examined using logistic regression. Overall, 61% reported high levels of satisfaction with their career trajectory to-date. Higher salary (odds ratio [OR] = 2.86, 95% confidence interval [95% CI]: 1.07-7.69) and having more leadership roles (OR = 2.26, 95% CI:1.04-4.90) were independently associated with higher career satisfaction. Persons with race/ethnicity other than white (OR = 0.40, 95% CI: 0.20-0.82) or age ≥ 50 (OR = 0.40, 95%CI: 0.17-0.94) had lower career satisfaction levels. There were no statistically significant differences in career satisfaction levels by gender, scientific discipline, or employment sector. 74% perceived their current salary as competitive, but persons with 5-9, or ≥10 years in their current position reported lower levels (OR = 0.31, 95% CI: 0.15-0.65; and OR = 0.37, 95% CI: 0.16-0.87, respectively), as did individuals in government positions (OR = 0.33, 95% CI: 0.11-0.98). These data add to the understanding of career satisfaction of those with advanced training in biomedical research by examining these measures in relation to prior postdoctoral research training and across multiple career sectors.

We sought to determine if maternal characteristics are associated with angiogenic profile in the first and second trimester of normotensive pregnancies.Circulating levels of maternal placental like growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt1), and soluble endoglin (sEng) were measured in serum samples collected during the first (median 11.3 weeks) and second trimester (median 17.1 weeks) of 182 normotensive pregnancies. Diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were measured at the same visits when samples were collected to measure angiogenic factors. Linear regression analysis was used to examine associations of the angiogenic measures with maternal characteristics. The association between blood pressure measures and concentrations of angiogenic factors was evaluated using Spearman correlation and linear regression analysis.In adjusted analyses, nulliparous women had higher sFlt1 concentrations in both first (p=0.06) and second (p=0.001) trimester. Higher BMI was associated with greater sFlt1 concentrations in both the first (p=0.004) and second trimester (p=0.008), but significantly lower sEng concentrations in both trimesters (p=0.002 for first trimester and p=0.0009 for second). Nulliparity and higher BMI also were associated with higher sFlt1/PLGF anti-angiogenic ratios in both first (p=0.05 and p=0.007, respectively) and second trimesters (p=0.003 and p=0.02, respectively). First trimester sFlt1 levels were weakly correlated with first trimester SBP (r(s)=0.18, p=0.03) and MAP (r(s)=0.16, p=0.04). Second trimester sEng levels were inversely associated with second trimester MAP (r(s)=-0.17, p=0.05). Including blood pressure measures in the linear regression models did not change the reported associations of angiogenic factors with maternal characteristics.These results demonstrate that even early in normotensive pregnancies maternal characteristics are associated with variations in angiogenic profile across this population.

Problem Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. preeclampsia) and spontaneous (e.g. preterm labor and membrane rapture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions.

Background: Studies support the hypothesis that high circulating levels of the hormone prolactin increase breast cancer risk. It remains unclear if genetic factors are associated with interindividual variation in circulating prolactin and subsequent breast cancer risk. We examined the relationship between single nucleotide polymorphisms (SNPs) in prolactin (PRL) and prolactin receptor (PRLR), serum prolactin levels and breast cancer risk in a population based case-control study. Methods: We genotyped 8 PRL and 20 PRLR tag SNPs in 1943 cases and 2229 controls (82% and 89% of enrolled, respectively). Cases were women 20-74 years old, diagnosed with in situ or invasive breast cancer between 2000 and 2003, and living in Warsaw or Lodz, Poland. Controls were cancer-free women selected from a population registry, matched to cases on age and city. Blood samples were provided at the study interview. Serum prolactin levels were measured in a subset of 773 controls using the Bayer Advia Centaur immunoassay. Odds ratios and 95% CIs for genotype-breast cancer associations were estimated using unconditional logistic regression, adjusting for age and city. Geometric mean prolactin levels and 95% confidence intervals (CI) were estimated using linear regression, adjusting for age, city, blood collection time, and day of menstrual cycle (premenopausal). Log-additive model Wald P-values were used to test for linear trends. Analyses were stratified by menopausal status, and all statistical tests were 2-sided (alpha=0.05). To account for multiple comparisons, P-values were adjusted using the Benjamini and Hochberg method. Results: Three PRLR SNPs were nominally associated with breast cancer: in premenopausal women, rs249537 (per-allele OR 1.39, 95% CI 1.07 - 1.82, P=0.0140); and in postmenopausal women, rs7718468 (per-allele OR 1.16, 95% CI 1.03 — 1.30, P=0.0137) and rs13436213 (per-allele OR 1.13 95% CI 1.01 — 1.26, P=0.0397). We examined serum prolactin levels by genotype for these three SNPs to determine whether the potential risk alleles were associated with increased circulating prolactin, but mean serum prolactin levels were similar by genotype in controls: rs249537 TT=3.83 ng/ml, CT=5.51 ng/ml, CC=5.50 ng/ml, P-trend=0.8381; rs7718468 CC=6.41 ng/ml, CT=6.86 ng/ml, TT=6.47 ng/ml, P-trend=0.5643; and rs13436213 AA=6.48 ng/ml, AG=6.52 ng/ml, GG=6.29 ng/ml, P-trend=0.4766. None of the nominal associations between PRLR genotypes and breast cancer risk were significant after adjusting for multiple comparisons (multiple comparison adjusted P-values: rs249537 P=0.4340; rs7718468 P=0.4340; rs13436213 P=0.8205). PRL SNPs were not associated with breast cancer risk in premenopausal or postmenopausal women. Discussion: Our data do not support an association between PRL or PRLR tag SNPs and breast cancer. Though some associations were nominally significant, these results may be due to random error and require further study. Furthermore, data do not support a relationship between riskassociated SNPs and differences in prolactin levels. Future research should focus on non-genetic factors that affect circulating prolactin levels. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-05.

Endogenous estrogen plays an integral role in the etiology of breast and endometrial cancer, and conceivably ovarian cancer. However, the underlying mechanisms and the importance of patterns of estrogen metabolism and specific estrogen metabolites have not been adequately explored. Long-standing hypotheses, derived from laboratory experiments, have not been tested in epidemiologic research because of the lack of robust, rapid, accurate measurement techniques appropriate for large-scale studies. We have developed a stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS(2)) method that can measure concurrently all 15 estrogens and estrogen metabolites (EM) in urine and serum with high sensitivity (level of detection=2.5-3.0fmol EM/mL serum), specificity, accuracy, and precision [laboratory coefficients of variation (CV's) < or =5% for nearly all EM]. The assay requires only extraction, a single chemical derivatization, and less than 0.5mL of serum or urine. By incorporating enzymatic hydrolysis, the assay measures total (glucuronidated+sulfated+unconjugated) EM. If the hydrolysis step is omitted, the assay measures unconjugated EM. Interindividual differences in urinary EM concentrations (pg/mL creatinine), which reflect total EM production, were consistently large, with a range of 10-100-fold for nearly all EM in premenopausal and postmenopausal women and men. Correlational analyses indicated that urinary estrone and estradiol, the most commonly measured EM, do not accurately represent levels of total urinary EM or of the other EM. In serum, all 15 EM were detected as conjugates, but only 5 were detected in unconjugated form. When we compared our assay methods with indirect radioimmunoassays for estrone, estradiol, and estriol and enzyme-linked immunosorbent assays for 2-hydroxyestrone and 16alpha-hydroxyestrone, ranking of individuals agreed well for premenopausal women [Spearman r (r(s))=0.8-0.9], but only moderately for postmenopausal women (r(s)=0.4-0.8). Our absolute readings were consistently lower, especially at the low concentrations characteristic of postmenopausal women, possibly because of improved specificity. We are currently applying our EM measurement techniques in several epidemiologic studies of premenopausal and postmenopausal breast cancer.

Absolute and relative concentrations of estrogens and estrogen metabolites are important for clinical decisions as well as for epidemiologic, experimental, and clinical research on hormonal carcinogenesis. RIA and ELISA are routinely used for measuring estrogen metabolites in blood and urine due to efficiency and low cost. Here, we compare absolute and ranked concentrations of estrone, estradiol, and estriol measured by indirect RIA and of 2-hydroxyestrone and 16α-hydroxyestrone measured by ELISA to the concentrations obtained using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures 15 estrogen metabolites concurrently. We used overnight urine samples collected from control women (362 premenopausal and 168 postmenopausal) participating in a population-based case-control study of breast cancer among Asian American women ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute concentrations for the five estrogen metabolites ranged from 1.6 to 2.9 and 1.4 to 11.8 times higher in premenopausal and postmenopausal women, respectively (all P < 0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r (rs) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and moderately correlated (rs = 0.4-0.8) in postmenopausal women. Measurements of the 2-hydroxyestrone:16α-hydroxyestrone ratio, a putative biomarker of breast cancer risk, were moderately correlated in premenopausal women (rs = 0.6-0.7) but only weakly correlated in postmenopausal women (rs = 0.2). LC-MS/MS had higher intraclass correlation coefficients (≥99.6%) and lower coefficients of variation (≤9.4%) than ELISA (≥97.2% and ≤14.2%) and RIA (≥95.2% and ≤17.8%). Comparison with the LC-MS/MS method suggests that the widely used RIA and ELISA estrogen metabolite measures may be problematic, especially at low estrogen metabolite levels characteristic of postmenopausal women. Cancer Epidemiol Biomarkers Prev; 19(1); 292–300

Purpose Insulin-like growth factor 1 (IGF-1) levels are positively related to some cancers and negatively related to cardiovascular disease. These conditions are also related to insulin resistance and high body weight, leading to the hypothesis that IGF-1 levels may, in part, mediate the association of high body weight with these health outcomes. Using the National Health and Nutrition Examination Survey (NHANES) III population, we examined the associations between IGF-1, IGF binding protein-3 (IGFBP-3), and the IGF-1/IGFBP-3 molar ratio with anthropometric measures in a large, U.S. population-based study where these associations could also be stratified by race/ethnicity and gender. Methods The study population consisted of 3,168 women and 2,635 men (44% non-Hispanic white, 28.2% non-Hispanic black, and 27.7% Mexican-American). Anthropometric measures were obtained by trained personnel in the NHANES mobile examination centers. IGF-1 and IGFBP-3 were measured using immunoassays by staff at Diagnostic System Laboratories (DSL) Inc. (Webster, TX). Associations of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio with anthropometric variables across race/ethnicity and gender were evaluated by using linear regression modeling. Results Body mass index (BMI) was inversely associated with IGF-1 levels across all of the race/ethnicity and gender subgroups. In contrast, BMI, waist to hip ratio (WHR), and waist circumference were positively associated with IGFBP-3 levels only in non-Hispanic black men and non-Hispanic white women. The IGF-1/IGFBP-3 molar ratio was inversely associated with all anthropometric measures, except height, in all subgroups of the population. Conclusion The significant inverse associations of BMI with IGF-1 levels and of all anthropometric variables, except height, with the IGF-1:IGFBP-3 molar ratio in all subgroups do not support existing hypotheses that associations of excess weight with negative health outcomes, such as specific cancer diagnoses, are mediated through high IGF-1 levels.

The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy.

Animal and in vitro models of prostate cancer demonstrate high IL-10 levels result in smaller tumors, fewer metastases, and reduced angiogenesis compared to controls. We sought to examine the hypothesis that genotypes correlated with low IL-10 production may be associated with increased prostate cancer risk among Finnish male participants from the Alpha-tocopherol Beta-carotene Cancer Prevention Study. DNA from 584 prostate cancer cases and 584 controls was genotyped for four IL-10 alleles, -1082, -819, -592, and 210. DNA from more of the controls than cases failed to amplify, resulting in 509 cases and 382 controls with genotype data for -1082; 507 and 384 for -819; 511 and 386 for -592; and 491 and 362 for 210. Odds ratios for the association between the IL-10 genotypes and risk of prostate cancer or, among cases only, high-grade disease were calculated using logistic regression. In this population, the -819 TT and -592 AA low expression genotypes were highly correlated. These two genotypes also were associated with increased prostate cancer susceptibility (OR = 1.92, 95% CI 1.07-3.43 for -819) and, among cases, with high-grade tumors (OR = 2.56, 95% CI 1.26-5.20 for -819). These data demonstrate genotypes correlated with low IL-10 production are associated with increased risk of prostate cancer and with high-grade disease in this population.

The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures.

This article features qualitative data from in-depth interviews of alumni from a long-standing, structured, postdoctoral research training program. Alumni from diverse scientific disciplines and representing 25 years of the program’s history reflected on the training curriculum and career preparation as it relates to their current career path., Published evaluations of career preparation of alumni from long-standing postdoctoral fellowship programs in the biomedical sciences are limited and often focus on quantitative analysis of data from extant publicly available sources. Qualitative methods provide the opportunity to gather robust information about specific program elements from structured postdoctoral training programs and the influence of this training on subsequent career paths of alumni. In-depth interviews with a subset of the National Cancer Institute’s Cancer Prevention Fellowship Program (CPFP) alumni (n = 27), representing more than 25 years of the program’s history and multiple career sectors, were conducted to assess alumni reflections on the training environment and career preparation during their time in the CPFP. NVivo software was used to analyze data and identify major themes. Four main themes emerged from these interviews, including: the value of structured training curriculum, mentorship, transdisciplinary environment, and professional identity. Even when reflecting on training that occurred one to two decades earlier, alumni were able to highlight specific components of a structured postdoctoral training program as influencing their research and career trajectories. These results may have relevance for those interested in assessing how postdoctoral training can influence fellows throughout their careers and understanding salient features of structured programs.

The purpose of this study was to examine the career paths of alumni from the National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP), a structured in-house postdoctoral training program of 3-4 years duration, and specifically what proportion of the alumni were currently performing cancer prevention-related activities. The analyses here included 119 CPFP alumni and 85 unsuccessful CPFP applicants, all of whom completed postdoctoral training between 1987-2011 and are currently employed. Postdoctoral training experiences and current career outcomes data were collected via online surveys. Differences between groups were assessed using chi-square and Fisher's exact test p-values and subsequent regression analyses adjusted for differences between the groups. Compared to 15.3% of unsuccessful CPFP applicants, 52.1% of CPFP alumni (odds ratio [OR] = 4.99, 95% confidence interval [95% CI): 1.91-13.0) were currently spending the majority of their time working in cancer prevention. Among those doing any cancer prevention-focused work, 54.3% of CPFP alumni spent the majority of their time performing cancer prevention research activities when compared to 25.5% of unsuccessful applicants (OR = 4.26, 95% CI: 1.38-13.2). In addition to the independent effect of the NCI CPFP, scientific discipline, and employment sector were also associated with currently working in cancer prevention and involvement in cancer prevention research-related activities. These results from a structured postdoctoral training program are relevant not only to the cancer prevention community but also to those interested in evaluating alignment of postdoctoral training programs with available and desired career paths more broadly.

Background: Prolactin is a peptide hormone necessary for normal breast development that may contribute to breast tumorigenesis. Estrogen is a significant positive regulator of prolactin synthesis; therefore, raloxifene, a selective estrogen receptor modulator under study as a breast cancer prevention agent, may modulate both estradiol and prolactin levels by inhibiting estradiol from binding to its receptor. Methods: Premenopausal women at increased risk for invasive breast cancer participated in a pilot chemoprevention trial and were given 60 mg raloxifene daily for 24 months. Fasting serum samples collected at baseline and after 12 months on drug were used to measure circulating prolactin, estradiol, and sex hormone binding globulin (SHBG) levels. Results: Of the 27 subjects who completed 12 months of raloxifene, 23 had paired prolactin samples, and 20 had paired estradiol and SHBG samples. Prolactin levels did not significantly change with raloxifene treatment, but SHBG levels increased (mean change = 7.3 nmol/L; P = 0.0001; 95% confidence interval, 3.9-10.7). Estradiol (mean change = 42 pg/mL; P = 0.048; 95% confidence interval, 1-84 pg/mL) levels were elevated when comparing 15 of the 20 women with paired estradiol measurements who also had both of these samples taken during the early follicular phase of the menstrual cycle. Conclusions: This report is the first to examine the long-term effects of raloxifene on prolactin, estradiol, and SHBG levels in premenopausal women who are also at increased risk for developing invasive breast cancer. Raloxifene had no significant effect on prolactin levels but did increase estradiol and SHBG measurements. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1153–8)

Cancer prevention postdoctoral fellowships have existed since the 1970s. The National Cancer Institute facilitated a meeting by a panel of experts in April 2013 to consider four important topics for future directions for cancer prevention postdoctoral training programs: (i) future research needs; (ii) underrepresented disciplines; (iii) curriculum; and (iv) career preparation. Panelists proffered several areas needing more research or emphasis, ranging from computational science to culture. Health care providers, along with persons from nontraditional disciplines in scientific training programs such as engineers and lawyers, were among those recognized as being underrepresented in training programs. Curriculum suggestions were that fellows receive training in topics such as leadership and human relations, in addition to learning the principles of epidemiology, cancer biologic mechanisms, and behavioral science. For career preparation, there was a clear recognition of the diversity of employment options available besides academic positions, and that program leaders should do more to help fellows identify and prepare for different career paths. The major topics and strategies covered at this meeting can help form the basis for cancer prevention training program leaders to consider modifications or new directions, and keep them updated with the changing scientific and employment climate for doctoral degree recipients and postdoctoral fellows. Cancer Epidemiol Biomarkers Prev; 23(4); 679–83. ©2014 AACR.

Previous studies have found an association between elevated circulating prolactin levels and increased risk of breast cancer. Prolactin stimulates breast cancer cell proliferation, migration, and survival via binding to the cell-surface prolactin receptor. The association of prolactin receptor expression with breast tumorigenesis remains unclear as studies that have focused on this association have had limited sample size and/or information about tumor characteristics. Here, we examined the association of prolactin expression with tumor characteristics among 736 cases, from a large population-based case–control study of breast cancer conducted in Poland (2000–2003), with detailed risk factor and pathology data. Tumors were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis of prolactin receptor expression. Association of prolactin receptor expression across strata of tumor characteristics was evaluated using χ 2 analysis and logistic regression. Prolactin receptor expression did not vary by menopausal status; therefore, data from pre- and post-menopausal women were combined in the analyses. Approximately 83 % of breast cancers were categorized as strong prolactin receptor staining. Negative/low prolactin receptor expression was independently associated with poorly differentiated (p = 1.2 × 10−08) and larger tumors (p = 0.0005). These associations were independent of estrogen receptor expression. This is the largest study to date in which the association of prolactin receptor expression with tumor characteristics has been evaluated. These data provide new avenues from which to explore the associations of the prolactin/prolactin receptor signaling network with breast tumorigenesis.

Ecologic studies support an inverse association between sunlight exposure and incidence of prostate cancer ([1][1]-[3][2]). Because sun exposure is the major source of human vitamin D production, several authors have hypothesized that the link between reduced prostate cancer incidence and increased

Successes in cancer prevention research over the past 60 years have altered clinical care and had broad implications for public health. Notable examples include the development of chemopreventive agents (e.g., tamoxifen reducing breast cancer risk), vaccines against infectious agents known to cause cancer (hepatitis B and human papillomavirus), screening and early detection targeting groups at higher risk (colonoscopy for ages 50 and older), and recommendations for lifestyle modifications, some of which have also been accompanied by policy efforts (smoking cessation programs and bans on smoking in public places).[1, 2] Yet despite these laudable advances, there is a pervasive sense among both the public and those in the field that “we should be further along in preventing cancer.” This rigorous science and decades of work required for discoveries to be translated into public health practice seem to be largely under-recognized by both the public and scientific community. When advances in cancer research are highlighted, prevention of cancer rarely takes center stage. Even in this time when emphasis is placed on finding higher quality, lower cost health interventions in general, the word ‘prevention’ may not even be mentioned.1 This state of affairs has led us to contemplate whether a new view of cancer prevention research training is necessary to energize this field and accelerate progress in preventing cancer.

The measurement of the protein hormone prolactin (PRL) in biological samples has developed over the years into a routine clinical assay aiding the diagnosis of multiple medical conditions. PRL is known to exist in multiple isoforms circulating throughout the body. Current methodologies for measuring the PRL levels typically involve a variety of immunoassays. However, most of these tests are not capable of distinguishing between the different isoforms. To address this need, we have developed a highly specialized method employing multiple reaction monitoring mass spectrometry (MRM-MS) capable of monitoring seven distinct peptides from two of the most common prolactin isoforms (the 23 kDa PRL and its 16 kDa N-terminal cleavage product). Since serum is the main source of clinical specimen for the measurement of prolactin isoforms, the method described in this chapter is focused on the approach to processing whole serum samples for prolactin analysis via reversed-phase liquid chromatography (RPLC) and MRM-MS.

The measurement of the protein hormone prolactin (PRL) in biological samples has developed over the years into a routine clinical assay aiding the diagnosis of multiple medical conditions. PRL is known to exist in multiple isoforms circulating throughout the body. Current methodologies for measuring the PRL levels typically involve a variety of immunoassays. However, most of these tests are not capable of distinguishing between the different isoforms. To address this need, we have developed a highly specialized method employing multiple reaction monitoring mass spectrometry (MRM-MS) capable of monitoring seven distinct peptides from two of the most common prolactin isoforms (the 23 kDa PRL and its 16 kDa N-terminal cleavage product). Since serum is the main source of clinical specimen for the measurement of prolactin isoforms, the method described in this chapter is focused on the approach to processing whole serum samples for prolactin analysis via reversed-phase liquid chromatography (RPLC) and MRM-MS.

The pregnancy-lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes.

To identify recent studies in the scientific literature that evaluated structured postgraduate public health and biomedical training programs and reported career outcomes among individual trainees, a comprehensive search of several databases was conducted to identify published studies in English between January 1995 and January 2012. Studies of interest included those that evaluated career outcomes for trainees completing full-time public health or biomedical training programs of at least 12 months duration, with structured training offered on-site. Of the over 600 articles identified, only 13 met the inclusion criteria. Six studies evaluated US federal agency programs and six were of university-based programs. Seven programs were solely or predominantly of physicians, with only one consisting mainly of PhDs. Most studies used a cohort or cross-sectional design. The studies were mainly descriptive, with only four containing statistical data. Type of employment was the most common outcome measure (n = 12) and number of scientific publications (n = 6) was second. The lack of outcomes evaluation data from postgraduate public health and biomedical training programs in the published literature is a lost opportunity for understanding the career paths of trainees and the potential impact of training programs. Suggestions for increasing interest in conducting and reporting evaluation studies of these structured postgraduate training programs are provided.

The Principles and Practice of Cancer Prevention and Control course (Principles course) is offered annually by the National Cancer Institute Cancer Prevention Fellowship Program. This 4-week postgraduate course covers the spectrum of cancer prevention and control research (e.g., epidemiology, laboratory, clinical, social, and behavioral sciences) and is open to attendees from medical, academic, government, and related institutions across the world. In this report, we describe a new addition to the Principles course syllabus, which was exclusively a lecture-based format for over 20 years. In 2011, cancer prevention fellows and staff designed and implemented small group discussion sessions as part of the curriculum. The goals of these sessions were to foster an interactive environment, discuss concepts presented during the Principles course, exchange ideas, and enhance networking among the course participants and provide a teaching and leadership opportunity to current cancer prevention fellows. Overall, both the participants and facilitators who returned the evaluation forms (n = 61/87 and 8/10, respectively) reported a high satisfaction with the experience for providing both an opportunity to explore course concepts in a greater detail and to network with colleagues. Participants (93 %) and facilitators (100 %) stated that they would like to see this component remain a part of the Principles course curriculum, and both groups provided recommendations for the 2012 program. The design, implementation, and evaluation of this initial discussion group component of the Principles course are described herein. The findings in this report will not only inform future discussion group sessions in the Principles course but may also be useful to others planning to incorporate group learning into large primarily lecture-based courses.

A history of a preeclamptic pregnancy has been associated with subsequent increased risk of cardiovascular disease in the mother and decreased risk of breast cancer in both the mother and offspring. The concentrations of steroid sex hormones, angiogenic factors, and other proteins during pregnancy are important components of the in utero environment and may mediate the association of preeclampsia with later health outcomes. This study sought to compare an extensive profile of biological markers in both maternal and umbilical cord samples in preeclamptic and uncomplicated pregnancies of a predominantly African-American population.Steroid sex hormones, angiogenic factors, and components of the insulin-like growth factor axis were measured in maternal and umbilical cord sera from 48 pregnancies complicated by preeclampsia and 43 uncomplicated pregnancies. Regression models estimated the associations of these markers with preeclampsia, after adjusting for maternal and gestational age.Concentrations of androgens (testosterone p = 0.06 and androstenedione p = 0.08) and the anti-angiogenic factors soluble fms-like kinase 1 (p = 0.004) and soluble endoglin (p = 0.004) were higher in the maternal circulation of women diagnosed with preeclampsia. These findings also were noted when the analyses were restricted to only African-American participants (77% of overall study population). Furthermore, among African-Americans, cord insulin-like growth factor-1 was lower in preeclamptic pregnancies than in controls.The associations of maternal androgens and anti-angiogenic factors with preeclampsia are consistent with prior reports from predominantly Caucasian populations. Alterations in these analytes as well as other maternal and fetal biomarkers in preeclampsia could mediate the associations of preeclampsia with later health consequences.

The Summer Curriculum in Cancer Prevention has been sponsored by the National Cancer Institute’s Cancer Prevention Fellowship Program for over two decades. This curriculum includes a four-week course entitled “Principles and Practice of Cancer Prevention and Control.” The ultimate goal of this course is to present the most current cancer prevention research to a diverse workforce of researchers and practitioners eager to address the current challenges in this field. The course covers the current status of cancer prevention research and practice, ranging from epidemiology and clinical practice, and from basic to behavioral science research. It is comprised of lectures grouped into nine modules representing broad and specific topics relevant to cancer prevention. Course participants come from a broad cross-section of career stages, professions, and research interests, and are from across the United States and other countries. Over time and in response to feedback from participants, the course has developed to meet the needs and expectations of this diverse audience, and may serve as a model for those interested in cancer prevention education and training in other countries.

Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. PE) and spontaneous (e.g. PL and membrane rupture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions.Thirty preterm singleton placentas from the following groups were analyzed: (i) severe PE, (ii) preterm premature membrane rupture (pPROM), and (iii) PL. Proinflammatory and anti-inflammatory cytokines, adhesion and angiogenic molecules were measured in placental lysates using a multiplex assay. K-means cluster analysis was used to generate patterns of protein level intensity.Three cluster patterns were apparent. Placentas from PE had high levels of vascular endothelial growth factor (VEGF) combined with low levels of acute inflammatory proteins (IL-1β, IL-18, IL-6, TNF-α), low IL-1 RA, and high transforming growth factor β (TGF-β). PL and pPROM had higher anti-inflammatory IL-1 RA and thrombomodulin combined with lower VEGF, regardless of proinflammatory cytokines and adhesion molecules. Half of the PL and pPROM cases had clusters of heightened inflammatory responses (lower TGF-β clustered with higher intensity of inflammatory mediators).Discriminating protein patterns were elucidated and may serve as a foundation from which to understand the biologic mechanisms underlying these pregnancy complications.

The Ninth Annual AACR International Conference on Frontiers in Cancer Prevention Research was held in Philadelphia. It is fitting to recognize that it was Philadelphia's famous resident Benjamin Franklin who stated that an ounce of prevention is worth a pound of cure. Like all valid scientific concepts, this notion has passed the test of time and represents a bedrock concept for the field of cancer prevention. The modern translation of these words constituted the overall theme of the meeting, “Prevention: From Basic Science to Public Health Benefit.” The meeting, which took place on November 7–10, 2010, featured 91 invited speakers, 11 proffered talks, 169 posters, and was attended by nearly 550 people and led to more than 1.7 million media reports. Educational sessions were offered on metabolomics, molecular epidemiology, epigenetics, and novel clinical trial design. Importantly, the meeting brought to light scientific advances that are transforming the field of cancer prevention. These advances provide us with the ability to understand the molecular underpinnings of carcinogenesis in humans and to identify and intervene in disease processes with unprecedented accuracy and power. Through translation of this knowledge we are now seeing benefits at the broad public health level. Recent scientific advances directly support the notion that this impact on public health will only increase. By its very nature, cancer prevention focuses on biological changes associated with the development and early progression of cancer, and on factors that can drive or mitigate such changes. Compared with investigations of advanced states of cancer, cancer prevention provides a relatively pure landscape that serves to optimize the interface between cancer biology, causative factors, and prospective intervention. It thereby provides a powerful platform to advance scientific understanding through which we can leverage highly efficacious intervention. These themes represented prominent highlights of the meeting.

Purpose Hemodilution refers to reduced concentrations of analytes in the blood secondary to increased fluid volume. Given that obesity is associated with expanded vascular volume, hemodilution may result in a lower ratio of blood concentrations of analytes among heavier subjects. Assessing the relationship of hormone concentration to total mass varies by body mass index (BMI) is etiologically important because obesity is related to hormone metabolism and cancer risk. Methods We evaluated data for 194 postmenopausal controls in an endometrial cancer case-control study. Height, weight, and serum hormone concentrations were measured previously. We estimated serum hormone mass from concentration based on estimates of calculated plasma volume. We assessed the effect of BMI on relationships of sex steroid hormone concentration and mass using multivariate linear regression. Results Higher BMI was associated with increased estrone, estrone sulfate, estradiol, and albumin-bound estradiol concentrations and masses ( p -trend ≤ 0.001). With increasing BMI, androstenedione concentration did not change significantly ( p -trend = 0.548), but its mass increased ( p -trend = 0.024). Conclusions Relationships of sex steroid hormone concentration and mass were generally similar, except for androstenedione in which the relationship was only significant for mass. Future studies to assess both sex steroid hormone concentration and mass may have value in etiological research.

The objective of this study was to comprehensively profile biological factors in pregnancy that have been postulated to be important components of the in utero environment and may also have relevance to later susceptibility to cancer and other chronic diseases.Steroid sex hormones, IGFs, and angiogenic factors were measured in maternal and cord serum from term normotensive pregnancies. Spearman correlations and linear regression estimated relationships among the biological factors and clinical characteristics.The analytes were generally not correlated between maternal and fetal circulations. However, significant correlations were demonstrated among several analytes within maternal or cord samples. A few analytes were associated with clinical characteristics (e.g., maternal IGF-1 and IGFBP-3 were inversely correlated with offspring birth weight, while maternal leptin and cord testosterone were positively correlated with this characteristic). Maternal androgens were higher in African-Americans than whites, and maternal PlGF and soluble fms-like tyrosine kinase-1 (sFlt-1) were higher in male than female offspring.There were significant correlations among analytes, but the patterns differed depending on whether they were measured in the maternal or fetal circulation. The number and magnitude of correlations among analytes, however, should affect the design and interpretation of future studies.

Prolactin (PRL) is a peptide hormone necessary for normal growth and development of the human breast. In addition, high levels of PRL in plasma correlate with increased risk of breast cancer, especially among postmenopausal women. Several isoforms of PRL exist in human circulation, including a 16-kDa isoform that is an N-terminal fragment of the full-length 23-kDa PRL. 16-kDa PRL has been shown to be antiangiogenic in vitro and in vivo and to reduce formation of tumors from prostate, colon, and melanoma cancer cell lines. Here, we explore the effect of 16-kDa PRL expression in vitro and in vivo using two breast cancer cell line models (MCF-7 and MDA-MB-231) and also the HCT-116 colon cancer cell line. In all three cell lines, 16-kDa PRL expression inhibited cell proliferation in vitro compared to empty vector controls. In vivo results were markedly different between the two types of cell lines. HCT-116 cells expressing 16-kDa PRL exhibited reduced vascularization and tumor formation, consistent with published results. The breast cancer cell lines expressing 16-kDa PRL also exhibited inhibition of angiogenesis in vivo but no reduction in tumor size or formation. These results suggest that the effects of 16-kDa PRL on tumor formation may vary across tissue types. The unique sensitivity of breast cancer to PRL as a mitogen and/or additional factors in the mammary gland environment (e.g., local hormone/mitogen concentration) may play a dominant role in tumor formation in vivo, thus outweighing the antiangiogenesis effects and in vitro reduction in cell proliferation induced by 16-kDa PRL.

There is a growing body of literature focused on endogenous hormone exposures during pregnancy and subsequent cancer risk for both mother and offspring. Examples of these studies include those focused on the biological mechanism for the association of preeclampsia with reduced risk of breast cancer for mother and female offspring or studies that have examined hormone concentrations during pregnancy between different ethnic groups who vary in their rates of breast cancer incidence. Although these studies seem relatively straightforward in conception and analysis, measurement of the concentration of hormones and other biomarkers in pregnant subjects is influenced by plasma volume expansion (PVE). During pregnancy, the maternal plasma volume expands 45% on average to provide for the greater circulatory needs of the maternal organs. Consequently, serum protein and hormone concentrations are greatly altered when comparing the pregnant with nonpregnant state. Assessing PVE also is complicated by the vast individual variation in PVE, ranging from minimal to a 2-fold increase. We propose that PVE needs to be evaluated when comparing biomarker concentrations during pregnancy in two populations that may differ with respect to PVE. Small body size is associated with lower PVE compared with higher body size. Therefore, we hypothesize that variation in PVE will influence the interpretation of differences in biomarker concentrations across population groups with respect to the etiologic significance of the biomarker to the disease under study (e.g., breast cancer). It is possible that some observations may be due only to differences in dilution between the two groups. We present PVE as a topic for consideration in population-based studies, examples of the types of studies where PVE may be relevant, and our own analysis of one such study in the text below. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1720–3)

The purpose of this study was to compare longitudinally sampled maternal angiogenic proteins between singleton and twin pregnancies.Placental growth factor (PlGF), soluble feline McDonough sarcoma (fms)-like tyrosine kinase (sFlt)-1, and soluble endoglin from healthy pregnant women were quantified at 10, 18, 26, and 35 weeks' gestation (n=91), and during the third trimester (31-39 weeks) and at delivery (33-41 weeks; n=41). Geometric means and 95% confidence intervals were calculated for gestational age-adjusted angiogenic protein concentrations and compared between matched twin and singleton pregnancies.Maternal sFlt-1 concentrations and the sFlt-1/PlGF ratio were higher in twins than singletons across pregnancy and at delivery, with the greatest differences at week 35 (sFlt-1: 36,916 vs 10,151 pg/mL; P.0001; sFlt-1/PlGF: 168.4 vs 29.0; P.0001). Maternal concentrations of soluble endoglin also were higher in the third trimester and delivery. Maternal PlGF concentrations were lower in twin than singleton pregnancies at week 35 only (219.2 vs 350.2 pg/mL; P.0001). Placental weight appeared to be inversely correlated with maternal sFlt-1/PlGF ratio at the end of pregnancy in both twins and singletons.Higher maternal antiangiogenic proteins in twin than singleton pregnancies does not appear to be due to greater placental mass in the former, and may be one explanation for the increased risk of preeclampsia in women carrying multiple gestations. Determining whether women with a history of multiple gestations have an altered cardiovascular disease and breast cancer risk, like those with a history of preeclampsia, is warranted.

Mutations within members of the EGF/ErbB receptor family frequently release the oncogenic potential of these receptors, resulting in the activation of downstream signaling events independent of ligand regulatory constraints. We previously have demonstrated that the signal transduction events originating from S3-v-ErbB, a ligand-independent, oncogenic EGF receptor mutant, are qualitatively distinct from the ligand-dependent mitogenic signaling pathways associated with the wild-type EGF receptor. Specifically, expression of S3-v-ErbB in primary fibroblasts results in anchorage-independent growth, increased invasive potential, and the formation of a transformation-specific phosphoprotein signaling complex, all in a Ras-independent manner. Here we demonstrate the transformation-specific interaction between two components of this complex: the adaptor protein Grb2 and the cytoskeletal regulatory protein caldesmon. This interaction is mediated via both the amino-terminal SH3 and central SH2 domains of Grb2, and the amino-terminal (myosin-binding) domain of caldesmon. Expression of a dominant-negative Grb2 deletion mutant, which lacks the carboxy-terminal SH3 domain, in fibroblasts expressing S3-v-ErbB results in a reduction in phosphoprotein complex formation, the loss of anchorage-independent growth, and a reduction in invasive potential. Together, these results demonstrate a Ras-independent role for Grb2 in modulating cytoskeletal function during ligand-independent EGF receptor-mediated transformation, and provide further support for the hypothesis that ligand-independent oncogenic signaling is qualitatively distinct from ligand-dependent mitogenic signaling by the EGF receptor.

Background: Prolactin is a peptide hormone that is important in growth and development of the human breast. Prolactin also induces migration, proliferation, and survival of cancer cells in vitro and mammary gland tumorigenesis in animal models. Recent studies suggest that elevated serum prolactin levels are related to increased breast cancer risk, but confirmation and extension of these results are needed. Accordingly, we analyzed associations of serum prolactin levels with breast cancer risk using data from a population-based breast cancer case-control study conducted in Poland. Methods: The Polish study included 2,386 consenting cases with pathologically confirmed breast cancer and 2,502 age and residency matched controls living in Warsaw and Lodz, Poland recruited during the years 2000 to 2003. Participation rates were 79% for cases and 69% for controls. This analysis included 773 cases and 776 controls with available serum and twofold representation of tumor in tissue microarrays. 70% of this study population was postmenopausal. Serum prolactin was measured by immunoassay at Quest Diagnostics. The overall CV for the prolactin serum assay was 99%. Detailed medical history and breast cancer risk factor information were obtained by interview. Tumor pathology data were collected via surgical pathology reports and independently reviewed in the U.S. Among controls, we assessed associations of prolactin levels with breast cancer risk factors using analysis of variance; case-control associations between breast cancer risk and prolactin levels (quartiles) were assessed by logistic regression. Results: Among premenopausal controls, nulliparity was inversely associated with prolactin levels (p=0.05), whereas among postmenopausal women, current/recent use of combined hormone replacement therapy (p Conclusions: Prolactin levels are significantly associated with breast cancer risk factors and risk for postmenopausal breast cancer. Our results confirm and extend prior studies focused on circulating prolactin levels and human breast cancer risk. Analyses examining associations between prolactin and tumor subclassifications based on immunological staining using tumor tissue microarrays are ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 861.

A93 Insulin-like growth factor-1 (IGF-1) levels are positively related to some cancers and negatively related to cardiovascular disease. These conditions are also related to insulin resistance and high body weight leading to the hypothesis that IGF-1 levels may, in part, mediate the association of high body weight with these health outcomes. Using the National Health and Nutrition Examination Survey (NHANES) III population, we examined the associations between IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 molar ratio with anthropometric measures in a large, United States population-based study where these associations could also be stratified by race/ethnicity and gender. The study population consisted of 3168 women and 2635 men who participated in NHANES III and provided a fasting morning serum sample. The study population was 44% non-Hispanic white, 28.2% non-Hispanic black, and 27.7% Mexican-American. On average, the female participants in the study were approximately 45 years old with a body mass index (BMI) of 26.3 while the male participants were approximately 43 years old with a BMI of 26.9. Linear regression models were used to determine the associations of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio with anthropometric variables across race/ethnicity and gender. The anthropometric measures included height, weight, waist-to-hip ratio, waist circumference, sum of skinfolds, and percent body fat and were obtained by trained personnel in the NHANES mobile examination center. IGF-1 and IGFBP-3 were measured by staff at Diagnostic System Laboratories (DSL, Inc., Webster, TX). BMI, waist-to-hip ratio, and waist circumference were inversely associated with IGF-1 levels across all race/ethnicity and gender subgroups except for non-Hispanic black men. The magnitude of the regression coefficients differed across racial/ethnic groups. In contrast, very few anthropometric measures where significantly associated with IGFBP-3 levels. The exception to this is non-Hispanic black men, where all anthropometric measures except height were positively associated with IGFBP-3 levels. The IGF-1/IGFBP-3 molar ratio was inversely associated with all anthropometric measures, except height, in all subgroups of the population. In addition, when examining mean levels of biomarkers across tertile of BMI, Mexican-American men and women had the lowest levels of IGF-1 and non-Hispanic white men and women had the highest levels of IGFBP-3. For the IGF-1/IGFBP-3 molar ratio, non-Hispanic black men and women had the highest ratios across all tertiles of BMI. The racial and ethnic differences in the levels of IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 molar ratio and longitudinal evaluation of their associations with anthropometrics measures merit further investigation since IGF-1 levels have been hypothesized to be a contributor to many health outcomes. Our data are not consistent with the hypothesis that the association of high IGF-1 levels with health outcomes such as increased cancer risk is mediated through high BMI. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A93.