Ian Pagano

Dalhousie University, Halifax, Nova Scotia, Canada

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Publications (26)83.88 Total impact

  • Article: Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case-control studies.
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    ABSTRACT: Mammographic density is strongly and consistently associated with breast cancer risk. To determine if this association was modified by reproductive factors (parity and age at first birth), data were combined from four case-control studies conducted in the United States and Japan. To overcome the issue of variation in mammographic density assessment among the studies, a single observer re-read all the mammograms using one type of interactive thresholding software. Logistic regression was used to estimate odds ratios (OR) while adjusting for other known breast cancer risk factors. Included were 1,699 breast cancer cases and 2,422 controls, 74% of whom were postmenopausal. A positive association between mammographic density and breast cancer risk was evident in every group defined by parity and age at first birth (OR per doubling of percent mammographic density ranged between 1.20 and 1.39). Nonetheless, the association appeared to be stronger among nulliparous than parous women (OR per doubling of percent mammographic density = 1.39 vs. 1.24; P interaction = 0.054). However, when examined by study location, the effect modification by parity was apparent only in women from Hawaii and when examined by menopausal status, it was apparent in postmenopausal, but not premenopausal, women. Effect modification by parity was not significant in subgroups defined by body mass index or ethnicity. Adjusting for mammographic density did not attenuate the OR for the association between parity and breast cancer risk by more than 16.4%, suggesting that mammographic density explains only a small proportion of the reduction in breast cancer risk associated with parity. In conclusion, this study did not support the hypothesis that parity modifies the breast cancer risk attributed to mammographic density. Even though an effect modification was found in Hawaiian women, no such thing was found in women from the other three locations.
    Breast Cancer Research and Treatment 01/2012; 132(3):1163-71. · 4.43 Impact Factor
  • Article: Equol production changes over time in pre-menopausal women.
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    ABSTRACT: Equol (EQ) is a metabolite produced by gut bacteria through the chemical reduction of the soya isoflavone daidzein (DE), but only by 30-60% of the population. EQ is believed to provide benefits derived from soya intake and its production is widely viewed as a relatively stable phenomenon. In a randomised, cross-over intervention with soya foods, seventy-nine pre-menopausal women were challenged with a high-soya and a low-soya diet each for 6 months, separated by a 1-month washout period. Overnight urine was collected at three time points during each diet period and analysed for DE and EQ by liquid chromatography tandem MS. Remaining an EQ producer (EP) or non-producer (NP) or changing towards an EP or NP was assessed using an EQ:DE ratio of ≥0·018 combined with a DE threshold of ≥2 nmol/mg creatinine as a cut-off point. We observed 19 and 24% EP during the low-soya and high-soya diet periods, respectively, and found that 6-11% of our subjects changed EQ status 'within' each study period (on an average of 1·2 times), while 16% changed 'between' the two diet periods. The present finding challenges the widely held conviction that EQ production within an individual remains stable over time. The precise factors contributing to changes in EQ status, however, remain elusive and warrant further investigation.
    The British journal of nutrition 09/2011; 107(8):1201-6. · 3.45 Impact Factor
  • Article: Equol production changes over time in postmenopausal women.
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    ABSTRACT: Equol (EQ) is produced by intestinal bacteria from the soy isoflavone daidzein (DE) in 30%-60% of the population and is believed to provide benefits from soy intake. A robust EQ status definition is lacking, and it is uncertain whether EQ is formed consistently within an individual and ceases upon oral antibiotic treatment. In a randomized, double-blind, placebo-controlled soy intervention trial with 350 postmenopausal women, DE and EQ were analyzed by liquid chromatography/tandem mass spectrometry at baseline and every 6 months over 2.5 years in overnight urine, spot urine and plasma. Equol production changes and status (remaining an EQ producer or nonproducer or changing towards an EQ producer or nonproducer) were assessed. Equol status was determined most dependably by overnight urine applying as cutoff a ratio of EQ/DE≥0.018 with a DE threshold ≥2 nmol/mg creatinine: the soy and placebo groups had approximately 30% consistent EQ producers during the study, but 14% and 35%, respectively, changed EQ status (mean 1.4-1.7 times), while 27% and 17%, respectively, had antibiotic treatment (P<.01 for inverse association). No significant trend in change of EQ production or status was observed when overnight urine was limited to collections closest to before and after antibiotic treatment. Similarly, antibiotic type or class, duration, dose or time between antibiotic treatment and overnight urine collection showed no consistent influence on EQ production. Equol production can markedly change intraindividually over 2.5 years, and antibiotic treatment impacts it inconsistently. Factors other than antibiotic treatment must be considered as causes for EQ production changes.
    The Journal of nutritional biochemistry 07/2011; 23(6):573-9. · 4.29 Impact Factor
  • Article: Mammographic density and risk of breast cancer by adiposity: an analysis of four case-control studies.
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    ABSTRACT: The association of mammographic breast density with breast cancer risk may vary by adiposity. To examine effect modification by body mass index (BMI), the authors standardized mammographic density data from four case-control studies (1994-2002) conducted in California, Hawaii and Minnesota and Gifu, Japan. The 1,699 cases and 2,422 controls included 45% Caucasians, 40% Asians and 9% African-Americans. Using ethnic-specific BMI cut points, 34% were classified as overweight and 19% as obese. A single reader assessed density from mammographic images using a computer-assisted method. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. Modest heterogeneity in the relation between percent density and breast cancer risk across studies was observed (p(heterogeneity) = 0.08). Cases had a greater age-adjusted mean percent density than controls: 31.7% versus 28.5%, respectively (p <0.001). Relative to <20 percent density, the ORs for >35 were similar across BMI groups whereas the OR for 20-35 was slightly higher in overweight (OR = 1.69, 95% CI: 1.28, 2.24) and obese (OR = 1.62, 95% CI: 1.12, 2.33) than in normal weight women (OR = 1.49, 95% CI: 1.11, 2.01). Furthermore, limited evidence of effect modification by BMI of the OR per 10% increase in percent density (p(interaction) = 0.06) was observed, including subgroup analyses by menopausal status and in analyses that excluded women at the extremes of the BMI scale. Our findings indicate little, if any, modification by BMI of the effects of breast density on breast cancer risk.
    International Journal of Cancer 05/2011; 130(8):1915-24. · 5.44 Impact Factor
  • Article: Malignant mesothelioma: facts, myths, and hypotheses.
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    ABSTRACT: Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. J. Cell. Physiol. 227: 44-58, 2012. © 2011 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 03/2011; 227(1):44-58. · 3.87 Impact Factor
  • Article: Factors affecting survival among women with breast cancer in Hawaii.
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    ABSTRACT: Given previous reports of ethnic differences in breast cancer survival among Hawaii's population, we investigated the role of adherence to treatment standards, treatment toxicity, preexisting chronic conditions, and obesity in the survival of 382 prospectively studied breast cancer patients representing six ethnic groups. Participants were recruited from several hospitals in Honolulu. Information on tumor characteristics and treatment was abstracted from medical records. Based on the Physicians Data Query (PDQ®), we assessed compliance with recommended treatment guidelines. Vital status and cause of death data were obtained through linkage with the Hawaii Tumor Registry. Cox proportional hazard models were used to compute hazard ratios for predictors of survival. After a median follow-up time of 13.2 ± 3.7 years, 115 deaths had occurred, 43 from breast cancer and 72 from other causes. After adjustment, we observed only small differences in survival by ethnicity that were not statistically significant. In addition to advanced disease stage, obesity at diagnosis was a significant independent predictor of worse and receiving PDQ-recommended treatment of better breast cancer-specific and all-cause survival. Developing high-grade toxicity was associated with worse breast cancer survival, whereas comorbidity and older age at diagnosis were associated with higher all-cause mortality. Hormone receptor status, menopausal status, and type of health insurance were not associated with survival. These findings suggest that given access to healthcare, breast cancer patients experience similar survival rates. Although more information about mechanisms of action would be useful, it appears reasonable to recommend weight control to breast cancer survivors.
    Journal of Women s Health 02/2011; 20(2):231-7. · 1.57 Impact Factor
  • Article: Mammographic density and hormone receptor expression in breast cancer: the Multiethnic Cohort Study.
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    ABSTRACT: It is unclear whether mammographic breast density, a strong risk factor for breast cancer, predicts subtypes of breast cancer defined by estrogen receptor (ER) and/or progesterone receptor (PR) expression. In a nested case-control study, we compared the breast density of 667 controls and 607 breast cancer cases among women of Caucasian, Japanese, and Native Hawaiian ancestry in the Hawaii component of the Multiethnic Cohort Study. A reader blinded to disease status performed computer assisted density assessment on prediagnostic mammograms. Receptor status was obtained from the statewide Hawaii Tumor Registry. Tumors were classified into ER+PR+ (n=341), ER-PR- (n=50), ER+PR-/ER-PR+ (n=64), and unstaged/unknown (n=152). Mean percent density values were computed for women with more than one mammogram. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) while adjusting for confounders. Mean percent density was significantly greater for ER+PR+ but not for ER-PR- tumors compared to controls after adjusting for age: 37.3%, 28.9% versus 29.4%, respectively. The overall OR per 10% increase in percent density were similar for ER+PR+ and ER+PR-/ER-PR+ tumors: 1.26 (95% CI 1.17-1.36) and 1.23 (95% CI 1.07-1.42), respectively. However, percent density was not found to be a predictor for ER-PR- tumors (OR 1.00, 95% CI 0.84-1.18). The results did not differ by ethnicity, nor by menopausal status, parity, or HRT use. Our findings indicate that within a multiethnic population, women with higher breast density have an increased risk for ER+PR+ but not ER-PR- tumors.
    Cancer epidemiology. 01/2011; 35(5):448-52.
  • Article: Urine accurately reflects circulating isoflavonoids and ascertains compliance during soy intervention.
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    ABSTRACT: Isoflavonoids (IFL) may protect against chronic diseases, including cancer. IFL exposure is traditionally measured from plasma (PL), but the reliability of urine is uncertain. We assessed whether IFL excretion in overnight urine (OU) or spot urine (SU) reliably reflects IFLs in PL and the usefulness of the three matrices to determine soy intake compliance. In a randomized, double-blind, placebo-controlled soy intervention trial with 350 postmenopausal women, IFLs (daidzein, genistein, glycitein, equol, O-desmethylangolensin, dihydrodaidzein, dihydrogenistein) were analyzed by liquid chromatography/mass spectrometry in OU, SU, and PL collected at baseline and every 6 months over 2.5 years. High between-subject intraclass correlations between all three matrices (median, 0.94) and high between-subject Pearson correlations (median r(OU-PL) = 0.80; median r(SU-PL) = 0.80; median r(OU-SU) = 0.92) allowed the development of equations to predict IFL values from any of the three matrices. Equations developed from a randomly selected 87% of all available data were valid because high correlations were found on the residual 13% of data between equation-generated and measured IFL values (median r(OU-PL) = 0.86; median r(SU-PL) = 0.78; median r(OU-SU) = 0.84); median absolute IFL differences for OU-PL, SU-PL, and OU-SU were 8.8 nmol/L, 10.3 nmol/L, and 0.28 nmol/mg, respectively. All three matrices showed highly significant IFL differences between the placebo and soy intervention group at study end (P < 0.0001) and highly significant correlations between IFL values and counted soy doses in the intervention group. OU and SU IFL excretion reflect circulating PL IFL levels in healthy postmenopausal women accurately. Noninvasively-collected urine can be used to reliably determine systemic IFL exposure and soy intake compliance.
    Cancer Epidemiology Biomarkers &amp Prevention 07/2010; 19(7):1775-83. · 4.12 Impact Factor
  • Article: Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients With Advanced Cancer to Select a Phase II Dose.
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    ABSTRACT: ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.
    Journal of Dietary Supplements 01/2009; 6(4):347-59.
  • Article: Complementary and alternative medicine.
    Ian Pagano
    Hawaii medical journal 06/2008; 67(5):136-7.
  • Article: IGF-I and mammographic density in four geographic locations: a pooled analysis.
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    ABSTRACT: Insulin-like growth factor (IGF-I) and prolactin have been found to be associated with breast cancer risk and with mammographic density. In a pooled analysis from 4 geographic locations, we investigated the association of percent mammographic density with serum levels of IGF-I, IGFBP-3 and prolactin. The pooled data set included 1,327 pre- and postmenopausal women: Caucasians from Norway, Arizona and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. Serum samples were assayed for IGF-I, IGFBP-3 and prolactin levels using ELISA assays. Mammographic density was quantified using a computer-assisted density method. After stratification by menopausal status, multiple regression models estimated the relation between serum analytes and breast density. All serum analytes except prolactin among postmenopausal women differed significantly by location/ethnicity group. Among premenopausal subjects, IGF-I levels and the molar ratio were highest in Hawaii, intermediate in Japan and lowest in Arizona. For IGFBP-3, the order was reversed. Among postmenopausal subjects, Norwegian women had the highest IGF-I levels and women in Arizona had the lowest while women in Japan and Hawaii had intermediate levels. We observed no significant relation between percent density and IGF-I or prolactin levels among pre-and postmenopausal women. The significant differences in IGF-I levels by location but not ethnicity suggest that environmental factors influence IGF-I levels, whereas percent breast density varies more according to ethnic background than by location. Based on this analysis, the influence of circulating levels of IGF-I, IGFBP-3, and prolactin on percent density appears to be very small.
    International Journal of Cancer 11/2007; 121(8):1786-92. · 5.44 Impact Factor
  • Article: Ethnic and geographic differences in mammographic density and their association with breast cancer incidence.
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    ABSTRACT: The objective of this pooled analysis was to compare differences in dense areas and percent mammographic densities to breast cancer incidence in populations at different breast cancer risk. The data set included 1,327 women aged 40-80: Caucasians from Norway, Arizona, and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. One reader performed computer-assisted quantitative density assessment for all mammographic films. Multiple linear regression models evaluated the influence of the covariates on breast density. Spearman correlation coefficients (r (s)) estimated the association between breast density and breast cancer incidence for the seven populations. After adjustment for covariates, ethnicity, but not location, was significantly associated with breast density. In the full model, 19% of the variation in the dense areas and 46% in the variation of percent densities were explained by measured risk factors. Native Hawaiians had the largest dense areas and women in Japan the smallest, whereas percent densities were highest among Native Hawaiians and Japanese in Hawaii and lowest among Norwegian women. The mean age-adjusted dense area had the strongest association with breast cancer incidence (r (s) = 0.93, P = 0.003); the relation with percent density was considerably weaker (r (s) = 0.32, P = 0.48). The correlation between age-adjusted dense area and breast cancer incidence remained strong after selectively removing individual data points. This comparison of mammographic densities suggests that, on a group level, age-adjusted dense areas may reflect breast cancer incidence better than percent densities.
    Breast Cancer Research and Treatment 08/2007; 104(1):47-56. · 4.43 Impact Factor
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    Article: Lifestyle risk factors for chronic disease in a multiethnic population: an analysis of two prospective studies over a 20-year period.
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    ABSTRACT: This study investigated changes in risk factors in Hawaii over 20 years and compared health behaviors among ethnic groups with well-documented differences in disease risk. Comparison of scores of a Chronic Disease Risk Index (CDRI) in the population of two large population-based cohorts. The respective sample sizes for the two cohorts were 19,319 and 97,746 persons ages > or = 40 years of White, Chinese, Filipino, Japanese, and Native Hawaiian ancestry. The CDRI included smoking status, alcohol use, meat intake, fruit and vegetable consumption, and body mass index. Mean total and component scores were compared over time and by ethnic group after adjustment for age and education. We found a reduction in overall CDRI scores, ie, improved health profiles, for both men and women over time. Men, Native Hawaiians, and Whites had higher CDRI scores than women and Japanese, Chinese, and Filipinos due to their higher scores for smoking, alcohol use, and overweight, whereas nutritional intakes were similar in all ethnic categories. Smoking, alcohol use, and overweight increased over time in both men and women, whereas dietary composition appeared to improve. This analysis suggests an overall reduction in modifiable dietary and lifestyle risk factors in Hawaii over time. Persistent differences by sex and ethnic category indicate that interventions to modify lifestyle factors need to tailor messages to the groups at highest risk.
    Ethnicity & disease 02/2007; 17(4):597-603. · 0.90 Impact Factor
  • Article: Trends of breast cancer incidence and risk factor prevalence over 25 years.
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    ABSTRACT: To examine the trends in the prevalence of breast cancer risk factors in relation to breast cancer incidence trends and to explore whether the changes in risk factors differed by ethnicity in Hawaii over a 25-year period. We pooled 17 population-based epidemiological studies conducted in Hawaii between 1975 and 2001. The study population of 82,295 women included subjects of Caucasian, Japanese, Native Hawaiian, Chinese, and Filipino ancestry. We computed age-adjusted prevalence estimates by ethnic group for 5-year time periods. Logistic regression was used to evaluate trends over time. The prevalence of an early age at menarche, nulliparity, and parity of fewer than three children, but not that of a late age at first live birth, increased during the study period. Whereas current smoking decreased for all ethnicities over time, the age-adjusted prevalence of overweight, obesity, college education, and alcohol use increased. Trends differed by ethnicity. For Native Hawaiians, the prevalence of overweight, obesity, alcohol use and nulliparity rose over time. For Japanese, the prevalence of overweight, early age at menarche, and having fewer than three children increased. Caucasians showed an increasing prevalence of overweight, obesity, college education, and nulliparity. In Filipina women, we observed changes in reproductive behavior and increasing obesity. Despite a slowing trend for some breast cancer risk factors, the overall risk profile in this population may lead to further increases in breast cancer incidence. Different ethnic groups may benefit from specific prevention strategies.
    Breast Cancer Research and Treatment 08/2006; 98(1):45-55. · 4.43 Impact Factor
  • Article: Alcohol consumption and mammographic density in a multiethnic population.
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    ABSTRACT: This report examined the association between alcohol intake and breast cancer risk as assessed by mammographic densities in a multiethnic population. Information for this analysis was available from 2 previous investigations: a nutritional intervention study (The Breast, Estrogens, and Nutrition Study; BEAN) with 217 premenopausal women and a nested case-control study within The Multiethnic Cohort (MEC) with 1,250 primarily postmenopausal women. On the basis of self-reported alcohol intake from a validated food frequency questionnaire, women were categorized into abstainers (<1 drink/month), low (<1 drink/day) and high (>or=1 drink/day) alcohol consumers. On average, 3 mammograms were available per woman. Using mixed models, we calculated mean percent densities for each alcohol consumption category while adjusting for covariates. Mean alcohol intakes for women in the BEAN study and for cases and controls in the MEC study were 2.0, 2.7 and 1.8 drinks/week, respectively. Overall, the difference in densities between abstainers and the highest alcohol intake category was only 1-2% and the differences were not statistically significant. However, the difference was 3-5% for women aged 55-65 years and for breast cancer cases. In postmenopausal women without hormone replacement therapy (HRT), breast density increased by 2% for each higher alcohol intake category. Breast densities were also elevated for high alcohol consumers on estrogen-only therapy as compared to abstainers and low consumers, whereas combined HRT use was associated with higher mammographic densities independent of alcohol use. In conclusion, despite the low alcohol intake in our population, alcohol consumers had higher percent breast densities than did abstainers. The larger difference in some subgroups suggests that women with certain characteristics may be more susceptible to the influence of alcohol on breast density than others.
    International Journal of Cancer 05/2006; 118(10):2579-83. · 5.44 Impact Factor
  • Article: Trends and dietary determinants of overweight and obesity in a multiethnic population.
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    ABSTRACT: To describe trends in BMI among different ethnic groups in Hawaii and to explore the relation of nutrient and food intake with excess weight. We pooled demographic, anthropometric, and nutritional data derived from a detailed diet history for 159,683 participants of 18 population-based epidemiological studies conducted in Hawaii over a 25-year period. The age-adjusted prevalence of excess weight (BMI > or = 25 kg/m(2)) was estimated for 5-year intervals. To explore dietary determinants of excess weight, we computed odds ratios using logistic regression. During the study period, the prevalence of excess weight increased considerably among all ethnic groups. Native Hawaiians had the highest and Asian Americans had the lowest prevalence of excess weight at all times. Although the percentage of calories consumed from carbohydrates increased, the percentage of calories from fat decreased over time. On an individual level, fat and protein consumption predicted a higher BMI, and dietary fiber intake predicted a lower BMI. Similarly, a higher consumption of meat, poultry, and fish was related to excess weight, whereas fruit and vegetable intake were inversely associated with excess weight. After stratification by ethnicity, the associations were not materially altered among women, but carbohydrates seemed to have a stronger association with excess weight among Native Hawaiian and Japanese men than among white men. In this large ethnically diverse population, plant-based foods and dietary fiber emerged as a potential protective factor against excess weight regardless of ethnicity.
    Obesity 04/2006; 14(4):717-26. · 4.28 Impact Factor
  • Article: A longitudinal investigation of mammographic density: the multiethnic cohort.
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    ABSTRACT: Mammographic densities are hypothesized to reflect the cumulative exposure to risk factors that influence breast cancer incidence. This report analyzed percent densities over time and explored predictors of density change in relation to age. The study population consisted of 607 breast cancer cases and 667 frequency matched controls with 1,956 and 1,619 mammographic readings, respectively. Mammograms done over >20 years and before a diagnosis of breast cancer were assessed for densities using a computer-assisted method. Using multilevel modeling to allow for repeated measurements, we estimated the effect of ethnicity, case status, reproductive characteristics, hormonal therapy, body mass index, and soy intake on initial status and longitudinal change. After integrating the area under the percent density curve, cumulative percent density was compared with age-specific breast cancer rates in Hawaii. Percent densities decreased approximately 5.6% per 10 years but a nonlinear effect indicated a faster decline earlier in life. Cumulative percent densities and age-specific breast cancer rates increased at very similar rates; both standardized regression coefficients were >0.9. Japanese ancestry, overweight, estrogen/progestin treatment, and, to a lesser degree, estrogen-only therapy predicted a slower decline in densities with age. Case status and adult soy intake were related to higher densities whereas overweight and having any child were associated with lower densities at initial status. Risk factors that influence the decline in mammographic densities over time may be important for breast cancer prevention because cumulative percent densities may reflect the age-related increase in breast cancer risk.
    Cancer Epidemiology Biomarkers &amp Prevention 04/2006; 15(4):732-9. · 4.12 Impact Factor
  • Article: Trends and Dietary Determinants of Overweight and Obesity in a Multiethnic Population*
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    ABSTRACT: Objectives: To describe trends in BMI among different ethnic groups in Hawaii and to explore the relation of nutrient and food intake with excess weight.Research Methods and Procedures: We pooled demographic, anthropometric, and nutritional data derived from a detailed diet history for 159,683 participants of 18 population-based epidemiological studies conducted in Hawaii over a 25-year period. The age-adjusted prevalence of excess weight (BMI 25 kg/m2) was estimated for 5-year intervals. To explore dietary determinants of excess weight, we computed odds ratios using logistic regression.Results: During the study period, the prevalence of excess weight increased considerably among all ethnic groups. Native Hawaiians had the highest and Asian Americans had the lowest prevalence of excess weight at all times. Although the percentage of calories consumed from carbohydrates increased, the percentage of calories from fat decreased over time. On an individual level, fat and protein consumption predicted a higher BMI, and dietary fiber intake predicted a lower BMI. Similarly, a higher consumption of meat, poultry, and fish was related to excess weight, whereas fruit and vegetable intake were inversely associated with excess weight. After stratification by ethnicity, the associations were not materially altered among women, but carbohydrates seemed to have a stronger association with excess weight among Native Hawaiian and Japanese men than among white men.Discussion: In this large ethnically diverse population, plant-based foods and dietary fiber emerged as a potential protective factor against excess weight regardless of ethnicity.Keywords: excess weight, nutrition, trends, ethnicity, pooled study
    Obesity 03/2006; 14(4):717-726. · 4.28 Impact Factor
  • Article: Mammographic densities and circulating hormones: a cross-sectional study in premenopausal women.
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    ABSTRACT: Progestogens appear to influence breast density more than estrogens in postmenopausal women taking hormone replacement therapy (HRT), but little is known about the effect of circulating hormones on mammographic density among premenopausal women. This cross-sectional study explores the relationship of body weight and sex steroids with breast density. Luteal serum samples were analyzed for progesterone, estrone, estradiol, and sex hormone-binding globulin (SHBG). Mammograms were assessed for density using a computer-assisted method. We performed mediation tests using multiple linear regression models. Significant associations of SHBG and estradiol with percentage density disappeared after adjustment for body weight and other covariates, whereas the relationship between progesterone and breast density remained borderline significant. The mediation tests indicated that progesterone has a direct and an indirect effect on mammographic density. Our finding that progesterone shows a stronger association with percentage of mammographic density than estrogen agrees with clinical reports describing denser mammographic patterns among women taking HRT, although these women differ in menopausal status.
    The Breast 03/2006; 15(1):20-8. · 2.49 Impact Factor
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    Article: The association of mammographic density with ductal carcinoma in situ of the breast: the Multiethnic Cohort.
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    ABSTRACT: It is well established that women with high mammographic density are at greater risk for breast cancer than are women with low breast density. However, little research has been done on mammographic density and ductal carcinoma in situ (DCIS) of the breast, which is thought to be a precursor lesion to some invasive breast cancers. We conducted a nested case-control study within the Multiethnic Cohort, and compared the mammographic densities of 482 patients with invasive breast cancer and 119 with breast DCIS cases versus those of 667 cancer-free control subjects. A reader blinded to disease status performed computer-assisted density assessment. For women with more than one mammogram, mean density values were computed. Polytomous logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for two measurements of mammographic density: percentage density and dense area. Mammographic density was associated with invasive breast cancer and breast DCIS. For the highest category of percentage breast density (> or = 50%) as compared with the lowest (< 10%), the OR was 3.58 (95% CI 2.26-5.66) for invasive breast cancer and 2.86 (1.38-5.94) for breast DCIS. Similarly, for the highest category of dense area (> or = 45 cm2) as compared with the lowest (< 15 cm2), the OR was 2.92 (95% CI 2.01-4.25) for invasive breast cancer and 2.59 (1.39-4.82) for breast DCIS. Trend tests were significant for invasive breast cancer (P for trend < 0.0001) and breast DCIS (P for trend < 0.001) for both percentage density and dense area. The similar strength of association for mammographic density with breast DCIS and invasive breast cancer supports the hypothesis that both diseases may have a common etiology.
    Breast cancer research: BCR 02/2006; 8(3):R30. · 5.24 Impact Factor