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ABSTRACT: This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research.
Nutrition and Cancer 01/2009; 61(5):708-16. · 2.78 Impact Factor
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ABSTRACT: The present analysis investigated the effect of soya foods on serum levels of six inflammatory markers, leptin, adiponectin, monocyte attractant protein 1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), IL-6 and C-reactive protein (CRP), and their relationship with BMI and lifetime soya intake. We randomised twenty-four men to a high- (two daily servings with 30-35 mg isoflavones per serving) or a low-soya diet for 3 months. After a 1-month washout period, the men crossed over to the other treatment. We used a multiplex bead immunoassay to measure leptin, adiponectin, MCP-1 and MIP-1b and ELISA assays for IL-6 and CRP. The statistical analysis applied mixed models that incorporated the four repeated measurements. The men had a mean age of 58.7 (sd 7.2) years and a mean BMI of 28.4 (sd 4.9) kg/m2. We observed no significant intervention effect of the soya treatment on any of the six markers. After adjustment for age and ethnicity, highly significant associations of BMI and body weight with leptin and MCP-1 emerged. Men with high soya intake early in life also had higher levels of leptin and MCP-1, whereas no association was seen for soya intake during adulthood. MIP-1b, adiponectin, IL-6 and CRP were not related to BMI, body weight or soya intake at any time in life. No intervention effect of soya foods on markers of inflammation was observed in this small study, but adiposity and early-life soya intake were related to higher leptin and MCP-1 levels.
The British journal of nutrition 01/2009; 101(12):1740-4. · 3.45 Impact Factor
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ABSTRACT: The main objective was to examine the association between simple hysterectomy (without bilateral oophorectomy) and breast cancer risk. Because hysterectomy prevalence varies by ethnicity, the secondary objective was to examine whether inclusion of women with hysterectomies affects the estimates of breast cancer risk by ethnicity.
The Multiethnic Cohort study was assembled between 1993 and 1996 and included 68,065 women from Hawaii and Los Angeles, aged 45-75 years, without any missing information or bilateral oophorectomy. Hysterectomy status was self-reported. After 7.7 years median follow-up, 1,862 cases of invasive breast cancer were identified. Proportional hazards models were used to estimate relative risks (RR) while controlling for known risk factors.
Prevalence of simple hysterectomy varied from 12% to 29% among the ethnic groups (White, African American, Native Hawaiian, Japanese American, and Latina). Overall, hysterectomy was not associated with breast cancer risk (RR = 0.98). Although the RRs were nonsignificantly elevated by 15% in White women and nonsignificantly reduced by 15% in Latinas of non-US origin, the variation by ethnicity was not significant (p(interaction) = 0.48). The breast cancer risk associated with ethnicity was very similar when estimated with and without women with hysterectomies.
This study suggests that simple hysterectomy status does not alter breast cancer risk. Therefore, inclusion of women with simple hysterectomies does not substantially change estimated risk of breast cancer by ethnicity.
Cancer Causes and Control 12/2008; 20(5):539-47. · 2.88 Impact Factor
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ABSTRACT: Based on the hypothesis that isoflavones are absorbed more efficiently from fermented than from non-fermented soya foods, we compared the urinary isoflavonoid excretion (UIE) after intake of miso soup or soya milk. We recruited twenty-one women with Japanese ancestry who consumed standardized soya portions containing 48 mg isoflavones. On day 1, half the women consumed soya milk, the other half started with miso soup. On day 3, the subjects ate the other soya food and on day 5, they repeated the first food. Each participant collected a spot urine sample before and an overnight urine sample after soya food intake. All urine samples were analysed for daidzein, genistein and equol using LC-MS and were expressed as nmol/mg creatinine. We applied mixed models to evaluate the difference in UIE by food while including the baseline values and covariates. Relative to baseline, both groups experienced significantly higher UIE after consuming any of the soya foods. We observed no significant difference in UIE when soya milk was compared to miso soup (P = 0.87) among all women or in the seven equol producers (P = 0.88). Repeated intake of the same food on different days showed high reproducibility within subjects. These preliminary results indicate similar UIE after consuming a fermented soya food (miso) as compared to a non-fermented soya food (soya milk). Therefore, recommendations favouring fermented soya foods are not justified as long as the intestinal microflora is capable of hydrolysing the isoflavone glucosides from non-fermented soya foods.
The British journal of nutrition 09/2008; 100(2):424-9. · 3.45 Impact Factor
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ABSTRACT: Breast density, the radiographically opaque fraction of the breast in a mammogram, is one of the strongest biomarkers of breast cancer risk. However, younger populations do not typically have mammograms due to radiation concerns. This study explored a commercially available dual-energy X-ray absorptiometer (DXA) system as a low-dose method to measure breast fibroglandular density in adolescent girls. Eighteen girls (13-14 years old) indicated their breast development according to Tanner and underwent three dedicated DXA scans, two of their left and one of their right breasts. Total projected breast area was manually delineated on each image and percent fibroglandular volume density (%FGV), absolute fibroglandular volume (FGV), total breast area, and volume were computed. It was possible to image breasts representing all five Tanner stages; %FGV ranged from 31.9% to 92.2% with a mean of 71.1 +/- 14.8%, whereas FGV ranged from 80 to 270 cm(3) with a mean of 168 +/- 54 cm(3). Left and right breast %FGV were highly correlated (r(p) = 0.97, P < 0.0001) and of the same magnitude (P = 0.18). However, left total volume and FGV were larger than the right by 38 cm(3) (P = 0.04) and 19 cm(3) (P = 0.02), respectively. Total volume and FGV increased by Tanner stage, whereas %FGV did not. Our method had excellent precision for %FGV and moderate precision for FGV (root mean square SDs of 2.4% and 16.6 cm(3)). These pilot data indicate that dedicated DXA breast scans may be useful in studies exploring breast density in girls.
Cancer Epidemiology Biomarkers & Prevention 07/2008; 17(7):1709-13. · 4.12 Impact Factor
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ABSTRACT: Experimental and epidemiologic studies suggest that soy may promote weight loss.
The goal of this study was to examine the relation of soy intake with body weight over the lifespan of women with Caucasian, Japanese, and Native Hawaiian ancestry.
We assessed the relation between lifetime soy consumption and body mass index (BMI) among 1,418 women in Hawaii. All subjects reported anthropometric measures, regular diet, and soy intake throughout life. The lifetime soy questionnaire was completed again by a subset of 356 women 5 years after study entry and the kappa values indicated moderate agreement. We regressed soy intake on BMI at study entry and at age 21 while controlling for confounding variables, computed least square means, and performed trend tests.
Higher soy consumption in adulthood was related to a lower BMI (P=0.02). This association was only significant for Caucasian women and for postmenopausal subjects. The women in the highest category also experienced a smaller annual weight change since age 21 (by 0.05 kg/year) than the low soy intake group (P=0.02). We observed no association between early life soy intake and BMI. High vegetable consumption was significantly associated with a higher soy intake among Caucasian women.
In this study, women consuming more soy during adulthood had a lower BMI, but the relation was primarily observed for Caucasian and postmenopausal subjects. This indicates that the association may be due to other nutritional factors and behaviors common in women with high soy intake.
European Journal of Nutrition 05/2008; 47(3):138-44. · 2.75 Impact Factor
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ABSTRACT: Given the possible breast cancer preventive effects of isoflavones, substances with an estrogen-like structure occurring in soybeans, it is of interest to assess levels directly in the breast. The objective of this pilot study was to measure isoflavones in nipple aspirate fluid. In a pilot study with 11 women, nipple aspirate fluid and urine samples were collected at baseline and after 1 month of consuming two servings of soymilk per day. In a parallel investigation, one woman donated nipple aspirate fluid, blood, and urine on the same day after consuming different amounts of soy for 9 days. Nipple aspirate fluid was collected with an aspirator, diluted 1 : 11, and stored at -20 degrees C. Isoflavonoids in nipple aspirate fluid, serum, and urine were liquid-liquid extracted after enzymatic hydrolysis followed by liquid chromatography electrospray ionization high resolution tandem mass spectrometry analysis using triply C labeled internal isoflavonoid standards. After the 30-day soy intervention, median nipple aspirate fluid yield changed very little (P=0.47), whereas urinary isoflavonoid excretion (P=0.04) and isoflavonoid levels in nipple aspirate fluid (P=0.12) increased substantially. For the nine samples collected in one participant, isoflavonoids measured in nipple aspirate fluid, plasma, and urine were highly correlated with the number of daily soy servings and with each other. This pilot study indicates that isoflavonoids in nipple aspirate fluid are 10 times lower than in plasma and are closely related to levels of isoflavonoids in urine and plasma. These findings show that isoflavonoids are present in breast fluid and may act directly on breast tissue.
European Journal of Cancer Prevention 03/2008; 17(1):67-70. · 2.13 Impact Factor
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ABSTRACT: Obesity may increase the risk for non-Hodgkin's lymphoma (NHL) through an inflammatory pathway. We explored the relation of NHL with body size at different times in life within the Multiethnic Cohort that includes African Americans, Caucasians, Japanese, Latinos, and Native Hawaiians. Participants were 45 to 75 years old at recruitment in 1993 to 1996. This analysis included 87,079 men and 105,972 women with 461 male and 378 female NHL cases. We used Cox regression to model NHL risk with age as the time metric while adjusting for age at baseline, ethnicity, education, alcohol intake, and age at first live birth. Body weight and body mass index at age 21 were stronger predictors of NHL risk than anthropometric characteristics at baseline. For men, being in the highest quartile of body mass index and body weight at age 21 conferred a nonsignificant 86% and 41% higher NHL risk, respectively, whereas there was no association at baseline. For women, the risk associated with the highest quartile of weight at age 21 was 1.6 (P(trend) = 0.04), whereas women in the highest quartile at baseline had a nonsignificant risk of 27%. Height was positively related to NHL in men and women. Despite the small numbers, there was some consistency for risk estimates across ethnic groups and weak evidence for an association with NHL subtypes. These findings indicate that weight at age 21 may represent lifetime adiposity better than body weight at cohort entry. Alternatively, weight at age 21 may be more relevant for the etiology of NHL.
Cancer Epidemiology Biomarkers & Prevention 02/2008; 17(1):196-203. · 4.12 Impact Factor
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ABSTRACT: Mammographic density has been established as a strong risk factor for breast cancer while use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) has been associated with a reduction in risk of breast cancer. The hypothesis is that NSAIDs reverses the expression of prostaglandin E2, thereby reducing the local production of estrogens. This report describes the differences in mammographic densities by duration of NSAID use in a multiethnic population. Information for this analysis was available from two previous investigations: a nutritional intervention study with 218 women and a nested case-control study of breast density with 1274 women. On the basis of self-reported medication use from a questionnaire common to both investigations, women were categorized into no use, up to 1 year, 2-5 years, 6-10 years, and 11+ years. Screening mammograms were assessed for density using a computer-assisted method. We applied general linear models to calculate mean percent densities for each medication use category while adjusting for covariates. The analysis of the overall study population did not show a significant association between total NSAID use and mammographic density. Contrary to our hypothesis, women with long-term total NSAID use had non-significantly higher densities than non-users. In addition, the results differed by menopausal status. Whereas the trend of higher densities with longer duration of total NSAID use was significant among postmenopausal women, breast density was slightly lower among premenopausal women with long-term NSAID use. Experimental studies need to be performed to study the effect, if any, of NSAID use on breast density.
Breast Cancer Research and Treatment 12/2007; 112(1):133-9. · 4.43 Impact Factor
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ABSTRACT: We examined the association of breast cancer risk as assessed by mammographic density with dietary patterns in a case-control study nested within the Hawaii component of the multiethnic cohort. This analysis included 3512 prediagnostic mammograms from 1250 premenopausal and postmenopausal women. Mammographic density of the breast was quantified by a computer-assisted assessment method. All study participants completed a validated Food Frequency Questionnaire at entry into the multiethnic cohort. Factor analysis was performed to extract dietary patterns. We computed covariate-adjusted mean percentage densities by quartiles of factor scores using mixed models and weights to account for breast cancer prevalence in the population. Women in this study were primarily of Caucasian, Japanese or native Hawaiian ethnicity. The mean percentage density was 33%. The following three dietary patterns were identified: 'fat and meat', 'vegetables' and 'fruit and milk'. The differences in densities across quartiles of any patterns were relatively small and did not reach statistical significance. Women who had higher scores in the 'fat and meat' pattern had higher densities than those with lower scores (34.8 vs. 32.3%, P for trend=0.21). The 'vegetables' pattern and deep-yellow vegetable intake were weakly inversely associated with densities only among Japanese women (P for trend=0.13 and 0.03, respectively). Our findings indicated that meat and plant-based nutritional patterns are related to breast density. The influence of diet on mammographic densities, however, appears to be fairly small. Analyses of both dietary patterns and single dietary factors seem equally informative in examining dietary associations with percentage density.
European Journal of Cancer Prevention 11/2007; 16(5):409-14. · 2.13 Impact Factor
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Gertraud Maskarinec,
Yumie Takata,
Zhao Chen,
Inger Torhild Gram,
Chisato Nagata,
Ian Pagano,
Kentaro Hayashi,
Leslie Arendell,
Guri Skeie,
Sabina Rinaldi,
Rudolph Kaaks
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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
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ABSTRACT: Previous studies on nonsteroidal antiinflammatory drugs (NSAIDs) and breast cancer have produced mixed results. Incident invasive cases of breast cancer from the Multiethnic Cohort (African Americans, Caucasians, Japanese Americans, Latinas, and Native Hawaiians from Hawaii and California) were identified from 1993 to 2002. Data on aspirin, acetaminophen, and other NSAID (ibuprofen, naproxen, indomethacin) use were based on a self-administered questionnaire at baseline (1993-1996). Multivariate Cox proportional hazards models provided estimates of hazard rate ratios and 95% confidence intervals. The authors observed no associations between breast cancer risk and duration of aspirin use for current or past users (hazard rate ratio = 1.05, 95% confidence interval: 0.88, 1.25 and hazard rate ratio = 1.04, 95% confidence interval: 0.84, 1.27 for > or =6 years of use, respectively) compared with nonusers. However, duration of current other NSAID use was protective (hazard rate ratio = 0.70, 95% confidence interval: 0.51, 0.95 for > or =6 years of use; p(trend) = 0.01) against the risk of breast cancer, while past use was not (hazard rate ratio = 0.90, 95% confidence interval: 0.62, 1.30 for > or =6 years of use). Analyses by ethnicity and hormone receptor status showed that the protective effect of current other NSAID use was limited to Caucasians and African Americans and to women with at least one positive hormone receptor. This study found duration of current other NSAID use to be protective against breast cancer risk.
American journal of epidemiology 11/2007; 166(10):1150-8. · 5.59 Impact Factor
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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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ABSTRACT: This study sought to explore whether Native Hawaiian primary ethnic identity is associated with cigarette use among Native Hawaiian middle school students. This study also explored whether social influence, psychosocial and cultural factors are associated with cigarette use in this sample.
The data are from a cross-sectional survey of 1,695 Native Hawaiian middle school students at 22 public and private schools on five islands in Hawaii. A subset of these students from Native Hawaiian serving schools (N=136) completed additional measures of Hawaiian cultural variables.
Based on univariate analyses, students whose primary ethnic identification was Hawaiian were more likely to have tried smoking (p<0.001) and to be current smokers (p<0.05) as compared to those classified as part Hawaiian. However, these findings were no longer significant in multivariate analyses. Social influence variables (i.e. peer and parental smoking) were most influential in explaining both prior and current smoking. Attendance at public school was also an important factor in explaining previous (OR=2.43; 95% CI=1.74, 3.38) and current (OR=7.20; 95% CI=4.58, 11.32) smoking behavior. Finally, cultural variables such as valuing Hawaiian folklore, customs, activities and lifestyle were largely unassociated with smoking behavior among Native Hawaiian middle school youth.
Additional research is needed to understand what aspects of ethnic identity are associated with smoking behavior among Native Hawaiian youth. The strong influence of peer and parental smoking suggests the need for interventions that support the creation of social environments that discourage tobacco use.
Ethnicity and Health 07/2007; 12(3):227-44. · 1.64 Impact Factor
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ABSTRACT: The extent to which modifiable dietary factors may account for some of the variability demonstrated in mammographic density across ethnic groups is unknown. The purpose of this study was to provide pilot data describing the relationship between dietary variables and mammographic density in pre- and postmenopausal Hispanic and non-Hispanic white (NHW) women (N=238) ranging in age from 41 to 50 years (premenopausal only) or 56 to 70 years (postmenopausal only).
Using a cross-sectional design, computer-assisted density assessments were performed on mammograms of both breasts and averaged for analysis. The Arizona Food Frequency Questionnaire was used to estimate dietary intake.
Study participants were well educated and overweight, with mean mammographic densities ranging from 20.25% for postmenopausal Hispanic women to 46.94% for premenopausal NHW women. Hispanic women reported higher energy intake than NHW women, but energy-adjusted intake of other nutrients was generally comparable. There was preliminary evidence of ethnic variability in diet-mammographic density associations. Among premenopausal Hispanic women, density was inversely associated with dairy, calcium, and vitamin D intakes (P<or=0.05 for all). Among premenopausal NHW women, lower mammographic density was associated with greater intake of vegetables (P<or=0.05), and higher density was associated with greater fruit intake (P<or=0.05). Among postmenopausal Hispanic women, for every 4.54 increase in the polyunsaturated-to-saturated fat ratio, there was a 9.0% reduction in mammograph density.
These preliminary results suggest that a differential pattern of dietary nutrient associations with mammographic density could potentially exist among Hispanic and NHW women. These ethnic differences in diet and mammographic density associations need to be further explored in larger studies.
Menopause 02/2007; 14(2):243-50. · 3.76 Impact Factor
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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
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ABSTRACT: Achieving significant reductions in tobacco use by youth is an important challenge. There is a pressing need to develop and evaluate innovative strategies that stimulate youth involvement and are effective in multi-ethnic populations. This article describes an innovative tobacco prevention trial, and reports baseline characteristics of participants and findings about implementation of the curriculum.
The aim of Project SPLASH is to evaluate the impact of a school-based smoking prevention intervention that emphasizes active involvement of middle school students, on rates of smoking initiation and regular smoking in a multi-ethnic cohort of youth in Hawaii. Project SPLASH is a group randomized trial that compares a 2-year innovative intervention with a social influence prevention program, in 20 public schools in Hawaii. The main outcome is mean 30-day smoking prevalence rates.
The response rate was 78.4%. Approximately 1 in 4 students had tried smoking and 30-day smoking prevalence at baseline was 8%. Intervention and control groups were comparable in terms of tobacco use, gender, ethnicity, behavioral, environmental, and psychosocial characteristics. Differences in ethnic identification, socio-economic status, acculturation, and involvement in prevention activities may be due to chance. The intervention was well implemented by teachers across both the intervention and control school classes.
For this study, 20 schools in Hawaii with close to 4000 participating students were recruited. Student smoking behavior and curriculum implementation were comparable by group status. The intervention study has the potential to elucidate how youth respond to an intervention with student involvement that incorporates cognitive and social action components.
Journal of Cancer Education 02/2007; 22(1):56-61. · 0.76 Impact Factor
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ABSTRACT: Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val58 Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort.
Mammographic density, before diagnosis in cases, was quantified by using a validated computer-assisted method. Blood samples were genotyped by standard PCR/RFLP methods. Adjusted mean percent density was calculated by genotype using mixed models with the unstructured covariance option.
A positive association between the C allele in the CYP1A2*1F gene and percent density, but not the dense area, was suggested (p = 0.11). The relation was limited to controls (p = 0.045), postmenopausal women not using HRT (p = 0.08), and normal weight subjects (p = 0.046). We did not observe any relation between the COMT Val58 Met polymorphism and breast density.
The lack of an association between the CYP1A2 genotype and the size of the dense areas suggests an effect on the non-dense, i.e., fatty breast tissue. The discrepancies among studies may be due to differential susceptibility; changes in enzyme activity as a result of the CYP1A2*1F polymorphism may influence breast tissue differently depending on hormonal status. Larger studies with the ability to look at interactions would be useful to elucidate the influence of genetic variation in CYP1A2 and COMT on the risk of developing breast cancer.
BMC Cancer 02/2007; 7:30. · 3.01 Impact Factor
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ABSTRACT: The polymorphic gene NAT2 is a major determinant of N-acetyltransferase activity and, thus, may be responsible for differences in one's ability to bioactivate heterocyclic amines, a class of procarcinogens in cooked meat. An unusually marked geographic variation in enzyme activity has been described for NAT2. The present study re-examines the international direct correlation reported for meat intake and colorectal cancer (CRC) incidence, and evaluates the potential modifying effects of NAT2 phenotype and other lifestyle factors on this correlation. Country-specific CRC incidence data, per capita consumption data for meat and other dietary factors, prevalence of the rapid/intermediate NAT2 phenotype, and prevalence of smoking for 27 countries were used. Multiple linear regression models were fit and partial correlation coefficients (PCCs) were computed for men and women separately. Inclusion of the rapid/intermediate NAT2 phenotype with meat consumption improved the fit of the regression model for CRC incidence in both sexes (males-R (2) = 0.78, compared to 0.70 for meat alone; p for difference in model fit-0.009; females-R (2) = 0.76 compared to 0.69 for meat alone; p = 0.02). Vegetable consumption (inversely and in both sexes) and fish consumption (directly and in men only) were also weakly correlated with CRC, whereas smoking prevalence and alcohol consumption had no effects on the models. The PCC between NAT2 and CRC incidence was 0.46 in males and 0.48 in females when meat consumption was included in the model, compared to 0.14 and 0.15, respectively, when it was not. These data suggest that, in combination with meat intake, some proportion of the international variability in CRC incidence may be attributable to genetic susceptibility to heterocyclic amines, as determined by NAT2 genotype.
Cancer Causes and Control 12/2006; 17(9):1175-82. · 2.88 Impact Factor
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ABSTRACT: 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.
To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women.
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.
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.
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.
Public Health Nutrition 11/2006; 9(7):875-81. · 2.17 Impact Factor
