Yukiko Morimoto

Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort.

Background:Ethnic disparities in metabolic disease risk may be the result of differences in circulating adipokines and inflammatory markers related to ethnic variations in obesity and body fat distribution.Subjects/Methods:In a cross-sectional design, we compared serum levels of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in control subjects (321 men and 930 women) from two nested case–control studies conducted within the Multiethnic Cohort Study consisting of whites, Japanese Americans (JA), Latinos, African Americans (AA) and Native Hawaiians (NH). General linear models were applied to evaluate ethnic differences in log-transformed serum biomarker levels before and after adjusting for body mass index (BMI) at cohort entry.Results:In comparison to whites, significant ethnic differences were observed for all biomarkers except TNF-α. JA men and women had significantly lower leptin and CRP levels than whites, and JA women also had lower adiponectin levels. Leptin was significantly higher in AA women (P<0.01), adiponectin was significantly lower in AA men and women (P=0.02 and P<0.001), and CRP and IL-6 were significantly higher in AA men and women. Lower adiponectin (P<0.0001) and CRP (P=0.03) levels were the only biomarkers in NH women that differed from whites; no statistically significant differences were seen for NH men and for Latino men and women. When adjusted for BMI at cohort entry, the differences between the lowest and the highest values across ethnic groups decreased for all biomarkers except adiponectin in men indicating that ethnic differences were partially due to weight status.Conclusions:These findings demonstrate the ethnic variations in circulating adipokine and CRP levels before and after adjustment for BMI. Given the limitation of BMI as a general measure of obesity, further investigation with visceral and subcutaneous adiposity measures are warranted to elucidate ethnicity-related differences in adiposity in relation to disparities in obesity-related disease risk.

Alcohol and dietary fibre intakes affect circulating sex hormones among premenopausal women

BACKGROUND The association of alcohol and fibre intake with breast cancer may be mediated by circulating sex hormone levels, which are predictors of breast cancer risk. OBJECTIVE To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women. METHODS A total of 205 premenopausal women completed a validated food-frequency questionnaire at baseline and after 2 years; blood samples taken at the same time were analysed for circulating sex hormone concentrations, including oestrone (E1), oestradiol (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by radioimmunoassay. We used mixed models to estimate least-square means of sex hormone concentrations for alcohol intake categories and quartiles of dietary intake. RESULTS After adjustment for covariates, alcohol consumption was moderately associated with higher circulating oestrogen levels; those who consumed more than one drink per day had 20% higher E2 (Ptrend=0.07) levels than non-drinkers. In contrast, higher dietary fibre intake was associated with lower serum levels of androstenedione (-8% between the lowest and highest quartiles of intake, Ptrend=0.06), but not oestrogens. Similarly, consumption of fruits (-12%, Ptrend=0.03), vegetables (-9%, Ptrend=0.15) and whole grains (-7%, Ptrend=0.07) showed inverse associations with androstenedione levels. CONCLUSIONS The consistency of the observed differences in sex hormone levels associated with alcohol and fibre-rich foods indicates that these nutritional factors may affect sex hormone concentrations and play a role in breast cancer aetiology and prevention.

Soy consumption is not protective against diabetes in Hawaii: the Multiethnic Cohort

Based on the hypothesis that soy consumption may improve glucose tolerance, we examined the association of soy intake with diabetes risk in the Hawaii component of the Multiethnic Cohort. Among 29 719 Caucasian, 35 141 Japanese American and 10 484 Native Hawaiian men and women, 8564 incident diabetes cases were identified during 14 years of follow-up. Cox regression was used to calculate hazard ratios while adjusting for known confounders with stratifications by sex, ethnicity and weight status. We observed no protective effect of soy food consumption on diabetes risk in this population, which has a wide range of soy intakes though lower than in Asian populations. Indeed, higher soy food intake was associated with a weakly elevated diabetes risk across ethnic groups; the higher risk was limited to overweight and obese individuals. The current findings do not support a protective effect of modest levels of soy food consumption against diabetes.

Serum prostate-specific antigen but not testosterone levels decrease in a randomized soy intervention among men

Background:Low prostate cancer incidence and high soy intake in Asian countries suggest a possible protective effect of soy foods against prostate cancer. The goal of this pilot study was to evaluate the feasibility of a randomized, crossover soy trial among men and to investigate the effects of daily soy intake on serum prostate-specific antigen (PSA) and testosterone levels.Methods:We randomized 24 men to a high or a low soy diet for 3 months. After a 1-month washout period, the men crossed over to the other treatment. During the high soy diet, the men consumed two daily soy servings; during the low soy diet, they maintained their usual diet. During the entire study each man donated four blood samples and five overnight urine samples. Dietary compliance was assessed by soy calendars, 24-h dietary recalls, and urinary isoflavone excretion measured by high-pressure liquid chromatography with photodiode array detection. Blood samples were analyzed for serum testosterone and PSA by radioimmunoassay. When necessary, variables were log transformed. Two sample t-tests compared the two groups before each study period. Mixed models incorporating the repeated measurements were used to evaluate the effect of the soy diet on urinary isoflavone excretion and serum analytes.Results:Twenty-three men aged 58.7±7.2 years completed the study. The compliance with the study regimen was high according to self-reported soy food intake and urinary isoflavone excretion. No significant between-group and within-group differences were detected. During the high soy diet, dietary isoflavone intake and urinary isoflavone excretion increased significantly as compared to the low soy diet. A 14% decline in serum PSA levels (P=0.10), but no change in testosterone (P=0.70), was observed during the high soy diet in contrast to the low soy diet.Conclusion:The high adherence as shown by three measures of compliance in this pilot trial demonstrated the feasibility of an intervention based on soy foods among free-living men.

A priori-defined diet quality indexes and risk of type 2 diabetes: the Multiethnic Cohort

Aims/hypothesisDietary patterns have been associated with the incidence of type 2 diabetes, but little is known about the impact of ethnicity on this relationship. This study evaluated the association between four a priori dietary quality indexes and risk of type 2 diabetes among white individuals, Japanese-Americans and Native Hawaiians in the Hawaii component of the Multiethnic Cohort.MethodsAfter excluding participants with prevalent diabetes and missing values, the analysis included 89,185 participants (11,217 cases of type 2 diabetes). Dietary intake was assessed at baseline with a quantitative food frequency questionnaire designed for use in the relevant ethnic populations. Sex- and ethnicity-specific HRs were calculated for the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010 (AHEI-2010), the Alternate Mediterranean Diet Score (aMED) and the Dietary Approaches to Stop Hypertension (DASH).ResultsWe observed significant inverse associations between higher DASH index scores and risk of type 2 diabetes in white men and women, as well as in Japanese-American women and Native Hawaiian men, with respective risk reductions of 37%, 31%, 19% and 21% (in the highest compared with the lowest index category). A higher adherence to the AHEI-2010 and aMED diet was related to a 13–28% lower risk of type 2 diabetes in white participants but not in other ethnic groups. No significant associations with risk of type 2 diabetes were observed for the HEI-2010 index.Conclusions/interpretationThe small ethnic differences in risk of type 2 diabetes associated with scores of a priori-defined dietary patterns may be due to a different consumption pattern of food components and the fact that the original indexes were not based on diets typical for Asians and Pacific Islanders.

The preventable proportion of type 2 diabetes by ethnicity: the multiethnic cohort.

PURPOSE To estimate the population-attributable risk (PAR) associated with modifiable risk factors for diabetes among Caucasians, Native Hawaiians, and Japanese Americans in the Hawaii component of the Multiethnic Cohort. METHODS This analysis is based on 74,970 cohort participants ages 45-75 years who completed a questionnaire on demographics, diet, and lifestyle factors in 1993-1996. After a mean follow-up time of 12.1 (0.01-14.4) years, 8,559 diabetes cases were identified by self-report, a medication questionnaire, and through health plan linkages. Hazard ratios for diabetes and partial PARs for single and different combinations of modifiable risk factors were estimated. RESULTS Overweight, physical inactivity, high meat intake, no alcohol consumption, and smoking were positively associated with diabetes risk in all ethnic groups. The estimated PARs suggested that among men, 78%, and among women, 83%, of new diabetes cases could have been avoided if all individuals had been in the low risk category for all of the modifiable risk factors. The slightly lower PARs in Japanese Americans were not significantly different from those in Caucasian and Native Hawaiian subjects. CONCLUSIONS Although PARs varied slightly over ethnicity, our findings do not support ethnic-specific prevention strategies; interventions targeted at multiple behaviors are needed in all ethnic groups.

Non-Hodgkin Lymphoma and circulating markers of inflammation and adiposity in a nested case-control study: The Multiethnic Cohort

Background: Because immune dysfunction is thought to underlie the development of non-Hodgkin lymphoma (NHL), obesity and chronic inflammation may be involved in its etiology. We examined the association of prediagnostic inflammatory markers and adipokines with NHL risk. Methods: We conducted a nested case–control analysis (272 cases and 541 matched controls) within the Multiethnic Cohort. Luminex technology was used to measure a 10-plex panel of cytokines, ELISA assays for adipokines, and an autoanalyzer for C-reactive protein (CRP). ORs and 95% confidence intervals (CI) for tertiles of analytes were estimated by conditional logistic regression. Results: After a median time of 2.7 years from phlebotomy to diagnosis, interleukin (IL)-10 was significantly related to NHL risk (ORT3 vs. T1 = 3.07; 95%CI, 2.02–4.66; Ptrend < 0.001). TNF-α and IL-8 showed borderline elevated risks, whereas IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, and CRP were not associated with NHL. Leptin but not adiponectin was related to NHL risk (ORT3 vs. T1 = 0.48; 95%CI, 0.30–0.76; Ptrend < 0.001). Adjustment for body mass index did not substantially affect the risk estimates. Stratification by subtype indicated significant associations with IL-10 and leptin for follicular but not for diffuse large B-cell lymphoma. Excluding cases diagnosed less than 1 year after phlebotomy attenuated all associations. Conclusions: IL-10 was the only cytokine and leptin the only adipokine associated with NHL, but due to the short follow-up time, preclinical effects cannot be excluded. Impact: Although markers of inflammation and adiposity may provide new insights into the etiology of NHL, they need to be assessed many years before clinical diagnosis. Cancer Epidemiol Biomarkers Prev; 22(3); 337–47. ©2012 AACR.

Analysis of urinary estrogens, their oxidized metabolites, and other endogenous steroids by benchtop orbitrap LCMS versus traditional quadrupole GCMS

AbstractEstrogens and other endogenous steroids are known risk markers for cancer. Gas chromatography (GC) with mass spectrometry (MS) has traditionally predominated the analysis of estrogens and other endogenous steroids, but liquid chromatography (LC) MS is increasingly favored. Direct comparisons of the two technologies have hitherto not been performed. Steroids were analyzed from 232 urine samples of 78 premenopausal women in a blinded fashion by benchtop orbitrap LCMS and single quadrupole GCMS. Sixteen steroidal estrogens including oxidized metabolites could be analyzed by LCMS. LCMS–GCMS Spearman rank correlations of the major estrogens E1, E2, E3, 16α-OHE1, and 2-OHE1 were very high (r = 0.72–0.91), and absolute concentrations also agreed (<5% difference for E1, E2, E3, 16α-OHE1). LCMS allowed reinterrogation of the acquired data due to orbitrap technology, which permitted post-analysis quantitation of progesterone, cortisol, and cortisone (LCMS–GCMS Spearman rank correlations = 0.80–0.84; absolute difference, <7%; n = 137). GCMS allows the measurement of a wide range of steroids including non-polar analytes that escape the presented LCMS assay. In contrast, orbitrap-based LCMS can detect more estrogens, is faster, less costly, allows post-data acquisition reinterrogation of certain analytes that had not been targeted a priori, and requires much less urine. FigureOrbitrap based LCMS trace of steroids after hydrolysis and dansylation

Estrogen Levels in Nipple Aspirate Fluid and Serum during a Randomized Soy Trial

Background: On the basis of hypothesized protective effect, we examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum, possible indicators of breast cancer risk. Methods: In a crossover design, we randomized 96 women who produced 10 μL or more NAF to a high- or low-soy diet for 6 months. During the high-soy diet, participants consumed 2 soy servings of soy milk, tofu, or soy nuts (∼50 mg of isoflavones per day); during the low-soy diet, they maintained their usual diet. Six NAF samples were obtained using a FirstCyte aspirator. Estradiol (E2) and estrone sulfate (E1S) were assessed in NAF and estrone (E1) in serum only, using highly sensitive radioimmunoassays. Mixed-effects regression models accounting for repeated measures and left-censoring limits were applied. Results: Mean E2 and E1S were lower during the high-soy than the low-soy diet (113 vs. 313 pg/mL and 46 vs. 68 ng/mL, respectively) without reaching significance (P = 0.07); the interaction between group and diet was not significant. There was no effect of the soy treatment on serum levels of E2 (P = 0.76), E1 (P = 0.86), or E1S (P = 0.56). Within individuals, NAF and serum levels of E2 (rs = 0.37; P < 0.001) but not of E1S (rs = 0.004; P = 0.97) were correlated. E2 and E1S in NAF and serum were strongly associated (rs = 0.78 and rs = 0.48; P < 0.001). Conclusion: Soy foods in amounts consumed by Asians did not significantly modify estrogen levels in NAF and serum. Impact: The trend toward lower estrogen levels in NAF during the high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk. Cancer Epidemiol Biomarkers Prev; 20(9); 1815–21. ©2011 AACR.

Urinary sex steroid excretion levels during a soy intervention among young girls: a pilot study.

Soy intake early in life may protect against breast cancer later in life, possibly by altering sex hormone metabolism. We evaluated the feasibility of assessing urinary sex steroid excretion among 20 young girls aged 8–14 yr in an 8-wk trial. The girls consumed one daily soy serving, collected weekly overnight urine samples, and reported Tanner stages for breast and pubic hair development. Sex steroid excretion was measured in duplicate by gas chromatography-mass spectrometry and adjusted for urinary creatinine. The respective coefficients of variation for estrone, estradiol, estriol, testosterone, pregnanediol were 11.4%, 10.4%, 8.4%, 12.8%, and 4.6%. The statistical analysis included t-tests, Spearmans correlations, and analysis of variance. Seventeen girls completed the study and showed good compliance with the intervention strategy. We observed nonsignificant increases in total androgens (0.11 μg/mg creatinine) and total estrogens (0.001 μg/mg creatinine) and a nonsignificant decrease in pregnanediol (–0.03 μg/mg creatinine) during the study period. Higher Tanner stages for pubic hair development were associated with ninefold higher estrogen, fourfold higher androgen, and twofold higher pregnanediol excretions (P = 0.01, P < 0.001, and P = 0.047, respectively). Similar differences were observed after stratification by breast development and menarcheal status. The association of sex steroid levels with pubertal development supports the validity of the sex steroid measurements.