Weight change in older adults and mortality: the Multiethnic Cohort Study.

OBJECTIVE: To investigate the association between weight change in older adults and mortality in a multiethnic population. METHODS: We performed a prospective analysis using data on weight change between the baseline (1993-1996) and the 10-year follow-up (2003-2007) surveys in relation to subsequent mortality among 63 040 participants in the Multiethnic Cohort Study in Hawaii and California. The participants were African American, Native Hawaiian, Japanese American, Latino and white, aged 45-75 years at baseline, and did not report heart disease or cancer at either survey. RESULTS: During an average of 7.3 years of follow-up after the 10-year survey, 6623 deaths were identified. Compared with individuals whose weight remained stable (±2.5 kg), those who lost weight and those with the highest weight gain (>10 kg) were at increased risk of all-cause mortality, with the risks greater for the weight loss (hazard ratios (HR): 2.86; 95% confidence interval (95% CI): 2.62-3.11 for >10 kg) than the weight-gain group (HR: 1.25; 95% CI: 1.11-1.41 for >10 kg), thus resulting in a reverse J-shaped curve. Japanese Americans and Latinos had stronger associations of weight loss >10 kg with mortality than did African Americans, Native Hawaiians and whites. The increase in risk with weight gain >10 kg was greater for older (⩾55 years at baseline) than younger individuals, whereas the increase in mortality associated with weight loss was greater for the normal weight (<25 kg m-2 at baseline) participants and never smokers, compared with overweight/obese persons and current smokers, respectively. CONCLUSIONS: Our findings confirm the association between weight change and a higher mortality in a healthy, multiethnic population, with higher risks for weight loss than weight gain. On the basis of these observations, public health recommendation should focus on the prevention of weight loss, as well as weight stability within the non-obese range, for middle-aged and older adults.

Ethnic admixture affects diabetes risk in native Hawaiians: the Multiethnic Cohort.

BACKGROUND/OBJECTIVES: Obesity and diabetes rates are high in Native Hawaiians (NHs) who commonly have mixed ancestries. People of Asian ancestry experience a high risk of type 2 diabetes despite the relatively low body weight. We evaluated the impact of ethnic admixture on diabetes risk among NHs in the Multiethnic Cohort (MEC). SUBJECTS/METHODS: On the basis of self-reports, 11 521 eligible men and women were categorized into NH/white, NH/other, NH alone, NH/Asian and the most common three ancestry admixture, NH/Chinese/white. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the NH/white category as the reference group; covariates included known confounders-that is, body mass index (BMI), dietary and other lifestyle factors. RESULTS: The NH alone category had the highest proportion of overweight and obese individuals and the NH/Asian category the lowest proportion. During 12 years of follow-up after cohort entry at 56 years, 2072 incident cases were ascertained through questionnaires and health plan linkages. All NH categories had higher HRs than the NH/white category before and after adjustment for BMI. In the fully adjusted models, the NH/Asian category showed the highest risk (HR=1.45; 95% CI: 1.27-1.65), followed by NH/other (HR=1.20; 95% CI: 1.03-1.39), NH/Chinese/white (HR=1.19; 95% CI: 1.04-1.37) and NH alone (HR=1.19; 95% CI: 1.03-1.37). The elevated risk by Asian admixture was more pronounced in normal weight than overweight/obese individuals. CONCLUSIONS: These findings indicate that Asian admixture in NHs is associated with a higher risk for type 2 diabetes independent of known risk factors and suggest a role for ethnicity-related genetic factors in the development of this disease.

Nutritional factors and non-Hodgkin lymphoma survival in an ethnically diverse population: the Multiethnic Cohort.

BACKGROUND/OBJECTIVES: To understand the possible effect of modifiable health behaviors on the prognosis of the increasing number of non-Hodgkin lymphoma (NHL) survivors, we examined the pre-diagnostic intake of major food groups with all-cause and NHL-specific survival in the Multiethnic Cohort (MEC). SUBJECTS/METHODS: This analysis included 2339 participants free of NHL at cohort entry and diagnosed with NHL as identified by cancer registries during follow-up. Deaths were ascertained through routine linkages to state and national death registries. Cox proportional hazards regression was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and NHL-specific mortality according to pre-diagnostic intake of vegetables, fruits, red meat, processed meat, fish, legumes, dietary fiber, dairy products and soy foods assessed by food frequency questionnaire. RESULTS: The mean age at diagnosis was 71.8±8.5 years. During 4.5±4.1 years of follow-up, 1348 deaths, including 903 NHL-specific deaths, occurred. In multivariable models, dairy intake was associated with higher all-cause mortality (highest vs lowest tertile: HR=1.14, 95% CI 1.00-1.31, Ptrend=0.03) and NHL-specific (HR=1.16, 95% CI 0.98-1.37) mortality. Legume intake above the lowest tertile was related to significant 13-16% lower all-cause and NHL-specific mortality, whereas red meat and fish intake in the intermediate tertiles was associated with lower NHL-specific mortality. No association with survival was detected for the other food groups. CONCLUSIONS: These data suggest that pre-diagnostic dietary intake may not appreciably contribute to NHL survival, although the higher mortality for dairy products and the better prognosis associated with legumes agree with known biologic effects of these foods.

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

Fruit and vegetable consumption, ethnicity and risk of fatal ischemic heart disease.

OBJECTIVE: Mortality rates from ischemic heart disease vary among ethnic groups. Dietary intake of fruits and vegetables has been associated with a lower risk of ischemic heart disease, but ethnic-specific data are limited. DESIGN: Prospective cohort study. SETTING: Hawaii and Los Angeles County, between 1993 and 1996. PARTICIPANTS: These analyses included 164,617 adults age 45 to 75, representing five ethnic groups who were enrolled in the Multiethnic Cohort Study. Dietary data were collected at baseline using a validated food frequency questionnaire and fatal ischemic heart disease cases were identified up to December 31, 2001. Associations between fruit and vegetable consumption and fatal ischemic heart disease were examined using multivariate Cox proportional hazard models. RESULTS: The associations between fruit and vegetable intake and fatal ischemic heart disease were similar among the five ethnic groups. When data for the ethnic groups were combined, higher vegetable intake was associated with a protective effect against ischemic heart disease in men with all intake levels above 3.4 servings per day (over 6.6 servings per day: hazard ratio, 0.73; 95% confidence interval, 0.58-0.92). Inconsistent results were observed for women, where the protective association was observed only at mid-level vegetable intake levels, but not among women with the highest level of vegetable intake. There was no evidence of an association for fruit intake. CONCLUSIONS: Associations between fruit and vegetable intake and fatal IHD do not appear to vary among ethnic groups. Additional research is needed to clarify associations for fruit versus vegetable intake and impact on cardiovascular outcomes.

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.

Adherence to recommendations for fruit and vegetable intake, ethnicity and ischemic heart disease mortality.

BACKGROUND AND AIMS: Ischemic heart disease (IHD) accounts for one-third of annual deaths in the U.S. and mortality rates vary by ethnicity. The association between adherence to dietary guidelines for fruit and vegetable intake with IHD mortality among different ethnic groups has not previously been examined. METHODS AND RESULTS: A prospective cohort design was used to examine the incidence of fatal IHD among participants in the Multiethnic Cohort Study. Participants included 164,617 men and women from five ethnic groups: African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Cox proportional hazards models, stratified by ethnicity and sex, were used to examine associations between adherence with recommended dietary guidelines for fruit and vegetable intake and risk for fatal IHD. The results did not provide evidence that the association between adherence with dietary recommendations for fruit or vegetable intake and IHD mortality varies by ethnicity. Pooled data did provide evidence that adhering to the recommendations for vegetables lowered risk among men (RR = 0.84, 95% CI: 0.74-0.96) and women (RR = 0.80, 95% CI: 0.69-0.94). No significant effects were observed for fruit intake. CONCLUSIONS: The effect of dietary intake of fruit and vegetables did not vary by ethnicity, providing evidence that recommendations do not need to be individualized for these special populations. The protective effect observed for vegetable intake among both sexes confirms previous findings and supports the evidence base for promoting diet modification in this direction.

Contribution of meat to vitamin B12, iron and zinc intakes in five ethnic groups in the USA: implications for developing food-based dietary guidelines.

BACKGROUND: To describe the sources of meat and their contributions to vitamin B12, iron and zinc in five ethnic groups in the USA. METHODS: Dietary data for the Multiethnic Cohort, established in Hawaii and Los Angeles, were collected using a quantitative food frequency questionnaire from more than 215,000 subjects, aged 45-75 years at baseline (1993-1996). Participants included African American, Latino, Japanese American, Native Hawaiian and Caucasian men and women. Servings of meat items were calculated based on the US Department of Agriculture recommendations and their contributions to intakes of total meat, red meat, vitamin B12, iron and zinc were determined. RESULTS: Of all types of meat, poultry contributed the most to meat consumption, followed by red meat and fish among all ethnicities, except for Latino (born in Mexico and Central/South America) men who consumed more beef. Lean beef was the most commonly consumed red meat for all ethnic-sex groups (9.3-14.3%), except for Native Hawaiian and Japanese American men, and Japanese American women whose top contributor was stew/curry with beef/lamb and stir-fried beef/pork with vegetables, respectively. The contribution of meat was most substantial for zinc (11.1-29.3%) and vitamin B12 (19.7-40%) and, to a lesser extent, for iron (4.3-14.2%). CONCLUSIONS: This is the first large multiethnic cohort study to describe meat sources and their contributions to selected nutrients among ethnic minorities in the USA. These findings may be used to develop ethnic-specific recommendations for meat consumption aiming to improve dietary quality among these groups.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Food intake of individuals with and without diabetes across different countries and ethnic groups.

BACKGROUND/OBJECTIVES: Given the importance of nutrition therapy in diabetes management, we hypothesized that food intake differs between individuals with and without diabetes. We investigated this hypothesis in two large prospective studies including different countries and ethnic groups. SUBJECTS/METHODS: Study populations were the European Prospective Investigation into Cancer and Nutrition Study (EPIC) and the Multiethnic Cohort Study (MEC). Dietary intake was assessed by food frequency questionnaires, and calibrated using 24h-recall information for the EPIC Study. Only confirmed self-reports of diabetes at cohort entry were included: 6192 diabetes patients in EPIC and 13 776 in the MEC. For the cross-sectional comparison of food intake and lifestyle variables at baseline, individuals with and without diabetes were matched 1:1 on sex, age in 5-year categories, body mass index in 2.5 kg/m(2) categories and country. RESULTS: Higher intake of soft drinks (by 13 and 44% in the EPIC and MEC), and lower consumption of sweets, juice, wine and beer (>10% difference) were observed in participants with diabetes compared with those without. Consumption of vegetables, fish and meat was slightly higher in individuals with diabetes in both studies, but the differences were <10%. Findings were more consistent across different ethnic groups than countries, but generally showed largely similar patterns. CONCLUSIONS: Although diabetes patients are expected to undergo nutritional education, we found only small differences in dietary behavior in comparison with cohort members without diabetes. These findings suggest that emphasis on education is needed to improve the current behaviors to assist in the prevention of complications.

Ethnic differences in weight gain and diabetes risk: the Multiethnic Cohort Study.

AIM: To improve our understanding of excess body weight and risk for diabetes type 2, the study examined the influence of weight change in the Hawaii component, including 78,006 Caucasians, Japanese Americans and Native Hawaiians, of the Multiethnic Cohort Study. METHODS: Participants aged 58.5±9.2 years completed a questionnaire at cohort entry (Qx1), including weight at age 21, and a follow-up questionnaire 5 years later (Qx2). After 14 years of follow-up, 8892 incident diabetes cases were identified through self-reports or linkups with the major health plans in Hawaii. Cox regression analysis was applied, stratified by age and adjusted for confounders, to estimate hazard ratios (HRs). RESULTS: The mean weight gain from age 21 to Qx1 was 10.5±11.0 kg and, between Qx1 and Qx2, 0.8±5.6 kg. Diabetes risk showed a significant dose-response relationship with weight gain from age 21 (P<0.0001). The respective HRs for a weight gain of 5-10 kg and greater or equal to 25 kg were 1.8 (95% CI: 1.7-2.0) and 7.7 (95% CI: 7.1-8.4), while weight loss of greater than 5 kg significantly reduced diabetes risk (HR=0.7; 95% CI: 0.6-0.9). The interaction term of weight change since age 21 with ethnicity was also highly significant (P<0.0001). Compared with stable-weight Caucasians, the adverse effects of weight gain were more pronounced in those of Japanese and Native Hawaiian descent. Weight change between Qx1 and Qx2 conferred a smaller risk. CONCLUSION: These findings support the current public-health recommendations for weight control and particularly among ethnic groups at high risk for diabetes.

Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the breast and prostate cancer cohort consortium (BPC3).

CONTEXT: Sex steroids play a central role in breast cancer development. OBJECTIVE: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. DESIGN: Data on 700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). SETTING AND PARTICIPANTS: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. MAIN OUTCOME MEASURES: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. RESULTS: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. CONCLUSIONS: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.

Meat consumption and risk of type 2 diabetes: the Multiethnic Cohort.

OBJECTIVE: To examine the association of meat consumption with diabetes risk in the Hawaii component of the Multiethnic Cohort and to assess effect modification by ethnicity. DESIGN: A prospective cohort study. Baseline information on diet and lifestyle was assessed by questionnaire. The cohort was followed up for incident cases of diabetes, which were identified through self-reports, medication questionnaires, or health plan linkages. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for diabetes associated with quintile of meat consumption. SETTING: Hawaii, USA. SUBJECTS: A total of 29,759 Caucasian, 35,244 Japanese-American and 10,509 Native Hawaiian men and women, aged 45-75 years at baseline. RESULTS: During a mean follow-up time of 14 years, 8587 incident diabetes cases were identified. Intake of red meat was positively associated with diabetes risk in men (fifth v. first quintile: HR=1.43; 95% CI 1.29, 1.59) and women (fifth v. first quintile: HR=1.30; 95% CI 1.17, 1.45) in adjusted models. The respective HR for processed red meat intake were 1.57 (95% CI 1.42, 1.75) and 1.45 (95% CI 1.30, 1.62). The association for processed poultry was weaker than for processed red meat, and fresh poultry intake was not associated with diabetes risk. For men only, we observed significant interactions of ethnicity with the red and processed red meat associations, with Caucasians experiencing slightly higher risks than Japanese-Americans. CONCLUSIONS: Our findings support the growing evidence that red and processed meat intake increase risk for diabetes irrespective of ethnicity and level of BMI.

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.

Asian women have greater abdominal and visceral adiposity than Caucasian women with similar body mass index.

BACKGROUND: In the Multiethnic Cohort Study, Japanese Americans (JA) have lower mean body mass index (BMI) compared with Caucasians, but show a higher waist-to-hip ratio at similar BMI values and a greater risk of diabetes and obesity-associated cancers. OBJECTIVE: We investigated the abdominal, visceral and hepatic fat distribution in these Asian and Caucasian Americans. DESIGN: A cross-sectional sample of 60 female cohort participants (30 JA and 30 Caucasians), of ages 60-65 years and BMIs 18.5-40 kg m(-2), underwent anthropometric measurements and a whole-body dual energy X-ray absorptiometry (DXA) scan: a subset of 48 women also had abdominal magnetic resonance imaging (MRI). RESULTS: By design, JA women had similar BMIs (mean 26.5 kg m(-2)) to Caucasian women (27.1 kg m(-2)). JA women were found to have a significantly smaller hip circumference (96.9 vs 103.6 cm; P=0.007) but not a significantly lower DXA total fat mass (25.5 vs 28.8 kg; P=0.16). After adjusting for age and DXA total fat mass, JA women had a greater waist-to-hip ratio (0.97 vs 0.89; P<0.0001), DXA trunk fat (15.4 vs 13.9 kg; P=0.0004) and MRI % abdominal visceral fat (23.9 vs 18.5%; P=0.01) and a lower DXA leg fat mass (8.2 vs 10.0 kg; P=<.0001). Their MRI % subcutaneous fat (33.4 vs 30.2%; P=0.21) and % liver fat (5.8 vs 3.8%; P=0.06) did not significantly differ from that of Caucasian women. CONCLUSIONS: Our findings build on limited past evidence, suggesting that Asian women carry greater abdominal and visceral fat when compared with Caucasian women with similar overall adiposity. This may contribute to their elevated metabolic risk for obesity-related diseases.

The association of diabetes with colorectal cancer risk: the Multiethnic Cohort.

BACKGROUND: Diabetics have been found to have a greater risk of colorectal cancer than non-diabetics. METHODS: We examined whether this relationship differed by ethnic group, cancer site or tumour stage in a population-based prospective cohort, including 3549 incident colorectal cancer cases identified over a 13-year period (1993-2006) among 199 143 European American, African American, Native Hawaiian, Japanese American and Latino men and women in the Multiethnic Cohort. RESULTS: Diabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics (relative risk (RR)=1.19, 95% confidence interval (CI)=1.09-1.29, P-value (P)<0.001). Positive associations were observed for colon cancer, cancers of both the right and left colon, and cancers diagnosed at a localised and regional/distant stage. The association with colorectal cancer risk was significantly modified by smoking status (P(Interaction)=0.0044), with the RR being higher in never smokers (RR=1.32, 95% CI=1.15-1.53, P<0.001) than past (RR=1.19, 95% CI=1.05-1.34, P=0.007) and current smokers (RR=0.90, 95% CI=0.70-1.15, P=0.40). CONCLUSION: These findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer.

Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort.

BACKGROUND: Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries. METHODS: This case-control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status. RESULTS: The median excretion of daidzein was 0.173 nmol mg(-1) creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31-0.98, P(trend)=0.03) and seemed to apply to localized (P(trend)=0.08) as well as advanced or high-grade cancer (P(trend)=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk. CONCLUSION: Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study.

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii-Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06-1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (P(trend)=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

A Y chromosomal influence on prostate cancer risk: the multi-ethnic cohort study.

BACKGROUND: A Y chromosomal role in prostate cancer has previously been suggested by both cytogenetic findings and patterns of Y chromosomal gene expression. We took advantage of the well established and stable phylogeny of the non-recombining segment of the Y chromosome to investigate the association between Y chromosomal DNA variation and prostate cancer risk. METHODS: We examined the distribution of 116 Y lineages in 930 prostate cancer cases and 1208 controls from four ethnic groups from a cohort study in Hawaii and California. RESULTS: One lineage, found only among the Japanese group in our study, was associated with a statistically significant predisposition to prostate cancer (odds ratio (OR) = 1.63; 95% confidence interval (CI) 1.07 to 2.47), and, in particular, to high severity disease in younger individuals (OR = 3.89; 95% CI 1.34 to 11.31). CONCLUSIONS: This finding suggests that a Y chromosomal factor contributes significantly to the development of prostate cancer in Japanese men.