Risk Factors for Type 2 Diabetes in the Multiethnic Cohort.

OBJECTIVES: In this report, we investigated the association between established risk factors and type 2 diabetes (T2D) across 5 distinct ethnic groups and explored differences according to T2D definition within the Multiethnic Cohort (MEC) Study. METHODS: Using the full MEC, with participants in Hawaii and Los Angeles (N=172,230), we applied Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All participants completed questionnaires asking about demographics, anthropometrics, lifestyle factors, and regular diet. T2D status was determined from self-reported diagnosis/medication and Medicare claims. We assessed the associations between well-established risk factors and T2D in the full cohort, after stratification by ethnic group, according to the T2D definition, and in a biorepository subset. Effect modification by ethnicity was evaluated using Wald's tests. RESULTS: Overall, 46,500 (27%) participants had an incident T2D diagnosis after a mean follow-up of 17.1±6.9 years. All predictors were significantly associated with T2D: overweight (HR=1.74), obesity (HR=2.90), red meat intake (HR=1.15), short (HR=1.04) and long (HR=1.08) sleep duration, and smoking (HR=1.26) predicted a significantly higher T2D incidence, whereas coffee (HR=0.90) and alcohol (HR=0.78) consumption, physical activity (HR=0.89), and diet quality (HR=0.96) were associated with lower T2D incidence. The strength of these associations was similar across ethnic groups with noteworthy disparities for overweight/obesity, physical activity, alcohol intake, coffee consumption, and diet quality. CONCLUSIONS: These findings confirm the importance of known risk factors for T2D across ethnic groups, but small differences were detected that may contribute to disparate incidence rates in some ethnic groups, especially for obesity and physical activity.

Coffee intake and risk of type 2 diabetes: the Multiethnic Cohort.

OBJECTIVE: We evaluated the influence of coffee consumption on diabetes incidence among the Hawaii component of the Multiethnic Cohort (MEC). DESIGN: Prospective cohort. SETTING: Population-based sample residing in Hawaii. SUBJECTS: After exclusions, 75 140 men and women of Caucasian, Japanese American and Native Hawaiian ancestry aged 45-75 years were part of the current analysis. All participants provided information on diet and lifestyle through an FFQ. After 14 years of follow-up 8582 incident diabetes cases were identified using self-reports, medication questionnaires and health plan linkages. Hazard ratios (HR) and 95 % confidence intervals were calculated using Cox regression while adjusting for known covariates. RESULTS: The risk for diabetes associated with total coffee consumption differed by sex (P interaction < 0·0001). Women consuming ≥3 cups of any type of coffee daily had a significantly lower risk (HR = 0·66; 95 % CI 0·58, 0·77; P trend < 0·0001) than those reporting <1 cup/d, whereas the relationship in men was borderline (HR = 0·89; 95 % CI 0·80, 0·99; P trend = 0·09). The same difference by sex was seen for regular coffee consumption, with HR of 0·65 (95 % CI 0·54, 0·78; P trend < 0·0001) and 0·86 (95 % CI 0·75, 0·98; P trend = 0·09) in men and women, respectively. No significant association with diabetes was apparent for decaffeinated coffee in women (HR = 0·85; 95 % CI 0·72, 1·01; P trend = 0·73) or men (HR = 1·07; 95 % CI 0·93, 1·23; P trend = 0·71). Despite small differences by ethnicity, the interaction terms between coffee intake and ethnicity were not significant. CONCLUSIONS: In this multiethnic population, regular, but not decaffeinated, coffee intake was much more protective against diabetes in women of all ethnic groups than in men.

Oestrogen levels in serum and urine of premenopausal women eating low and high amounts of meat.

OBJECTIVE: Based on the hypothesis that high-meat diets may increase breast cancer risk through hormonal pathways, the present analysis compared oestrogens in serum and urine by meat-eating status. DESIGN: Intervention with repeated measures. SETTING: Two randomized soya trials (BEAN1 and BEAN2) among premenopausal healthy women. SUBJECTS: BEAN1 participants completed seven unannounced 24 h dietary recalls and donated five blood and urine samples over 2 years. BEAN2 women provided seven recalls and three samples over 13 months. Serum samples were analysed for oestrone (E1) and oestradiol (E2) using RIA. Nine oestrogen metabolites were measured in urine by LC-MS. Semi-vegetarians included women who reported consuming <30 g of red meat, poultry and fish daily, and pescatarians those who reported consuming <20 g of meat/poultry but >10 g of fish daily. All other women were classified as non-vegetarians. We applied mixed models to compute least-square means by vegetarian status adjusted for potential confounders. RESULTS: The mean age of the 272 participants was 41·9 (SD 4·5) years. Serum E1 (85 v. 100 pg/ml, P = 0·04) and E2 (140 v. 154 pg/ml, P = 0·04) levels were lower in the thirty-seven semi-vegetarians than in the 235 non-vegetarians. The sum of the nine urinary oestrogen metabolites (183 v. 200 pmol/mg creatinine, P = 0·27) and the proportions of individual oestrogens and pathways did not differ by meat-eating status. Restricting the models to the samples collected during the luteal phase strengthened the associations. CONCLUSIONS: Given the limitations of the study, the lower levels of serum oestrogens in semi-vegetarians than non-vegetarians need confirmation in larger populations.

Prediagnostic serum tocopherol levels and the risk of non-hodgkin lymphoma: the multiethnic cohort.

BACKGROUND: Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. METHODS: This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). RESULTS: We observed U-shaped associations with NHL for total and α-tocopherols [Ptrend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for α-tocopherol but nonsignificant for ß- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 ± 9.04 vs. 17.72 ± 7.43 µg/mL; P < 0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. CONCLUSIONS: Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. IMPACT: The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL.

It's time for clinicians to reconsider their proscription against the use of soyfoods by breast cancer patients.

The impact of soyfood intake on breast cancer risk has been intensely investigated. This focus can be attributed to soyfoods being uniquely rich dietary sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor (ER) modulators. The finding that dietary genistein, the primary soybean isoflavone, stimulates the growth of existing mammary tumors in ovariectomized athymic mice implanted with ER-positive breast cancer cells has led many oncologists to advise their patients against the use of soyfoods. However, the clinical evidence indicates that isoflavone exposure has little effect on markers of breast cancer risk. Furthermore, a pooled analysis that involved 9,514 breast cancer survivors found higher isoflavone intake was associated with a statistically significant 25% reduction in recurrence over the average 7.4-year follow-up period. Given the clinical and epidemiologic data, our position is that clinicians should allow soyfood use by patients for whom soyfoods already represent a normal part of their diet, and should not discourage other breast cancer survivors from moderate consumption.

The human mammary gland as a target for isoflavones: how does the relation vary in individuals with different ethnicity?

Based on observational studies, it appears that soy food consumption provides protection against breast cancer primarily in Asian but not in Western populations. Given the problems in examining the effects of isoflavones directly in the human mammary gland, this review describes epidemiologic studies that investigated the association with biomarkers reflecting hormonal activity of isoflavones, in particular sex steroid levels, mammographic densities, nipple aspirate fluid, and tissue specimens from biopsies or surgeries. Three possible mechanisms that may be responsible for ethnic-specific health effects from these compounds are discussed: genetic variation in metabolic enzymes, timing of exposure, and intestinal metabolism by microbiota. Only a limited number of comparative studies and even fewer nutritional interventions have examined effects and addressed differences in biomarkers between Asian and Western populations. Investigations that looked at estrogens and mammographic densities as endpoints observed some associations in Asian women that were not seen in Caucasians. On the other hand, the low rate of nipple aspirate fluid production and a lack of breast tissue studies make it impossible to evaluate effects of isoflavones on these biomarkers in Asian women. Based on the current evidence, it appears likely that the timing of exposure is the most important determinant of beneficial health effects from soy foods. This may be the result of gut microbiota, which colonize the intestine during childhood and facilitates the hydrolysis of glycosides and the formation of equol from dadzein, a pathway that may result in beneficial health effects. The current evidence is insufficient to answer the question whether women of diverse ethnic groups experience distinct effects from soy isoflavones in breast tissue, but as knowledge about the role of early life nutrition and the development of gut microbiota increases, the potential for diverse metabolic pathways of isoflavones in individuals with different ethnic backgrounds and dietary exposures may be clarified.

Complementary and alternative medicine use and breast cancer prognosis: a pooled analysis of four population-based studies of breast cancer survivors.

BACKGROUND: Complementary and alternative medicine (CAM) use is common among breast cancer survivors, but little is known about its impact on survival. METHODS: We pooled data from four studies conducted in Hawaii in 1994-2003 and linked to the Hawaii Tumor Registry to obtain long-term follow-up information. The effect of CAM use on the risk of breast cancer-specific death was evaluated using Cox regression. RESULTS: The analysis included 1443 women with a median follow-up of 11.8 years who had a primary diagnosis of in situ and invasive breast cancer. The majority were Japanese American (36.4%), followed by white (26.9%), Native Hawaiian (15.9%), other (10.6%), and Filipino (10.3%). CAM use was highest in Native Hawaiians (60.7%) and lowest in Japanese American (47.8%) women. Overall, any use of CAM was not associated with the risk of breast cancer-specific death (hazard ratio [HR] 1.47, confidence interval [CI] 0.91-2.36) or all-cause death (HR 0.82, 95% CI 0.63-1.06). However, energy medicine was associated with an increased risk of breast cancer-specific death (HR 3.19, 95% CI 1.06-8.52). When evaluating CAM use within ethnic subgroups, Filipino women who used CAM were at increased risk of breast cancer death (HR 6.84, 95% CI 1.23-38.19). CONCLUSIONS: Our findings suggest that, overall, CAM is not associated with breast cancer-specific death but that the effects of specific CAM modalities and possible differences by ethnicity should be considered in future studies.

Various doses of soy isoflavones do not modify mammographic density in postmenopausal women.

Soy isoflavones have functional similarity to human estrogens and may protect against breast cancer as a result of their antiestrogenic activity or increase risk as a result of their estrogen-like properties. We examined the relation between isoflavone supplementation and mammographic density, a strong marker for breast cancer risk, among postmenopausal women. The Osteoporosis Prevention Using Soy (OPUS) study, a multi-site, randomized, double-blinded, and placebo-controlled trial assigned 406 postmenopausal women to 80 or 120 mg/d of isoflavones each or a placebo for 2 y. Percent densities were assessed in digitized mammograms using a computer-assisted method. The mammogram reader did not know the treatment status and the time of mammograms. We applied mixed models to compare breast density by treatment while considering the repeated measures. The mammographic density analysis included 358 women, 88.2% of the OPUS participants; 303 had a complete set of 3 mammograms, 49 had 2, and 6 had only 1 mammogram. At baseline, the groups were similar in age, BMI, and percent density, but mean breast density differed by study site (P = 0.02). A model with all mammograms did not show a treatment effect on any mammographic measure, but the change over time was significant; breast density decreased by 1.6%/y across groups (P < 0.001). Stratification by age and BMI did not reveal any effects in subgroups. In this randomized 2-y trial, isoflavone supplements did not modify breast density in postmenopausal women. These findings offer reassurance that isoflavones do not act like hormone replacement medication on breast density.

Urinary isoflavonoid excretion is similar after consuming soya milk and miso soup in Japanese-American women.

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.

Understanding the motivation for conventional and complementary/alternative medicine use among men with prostate cancer.

HYPOTHESIS: The incidence of prostate cancer and the prevalence of complementary and alternative medicine (CAM) use among prostate cancer patients have been increasing. An understanding of the underlying motivations for men to turn to CAM is essential to achieve optimal outcomes. The authors hypothesized that CAM users and nonusers differ in their assessment of conventional and CAM treatments and explored perceptions, feelings, ideas, and experiences among prostate cancer patients who made a decision to use or not to use CAM. STUDY DESIGN: This qualitative study is based on in-person interviews with prostate cancer patients selected from a population-based survey. METHODS: The authors conducted semistructured interviews with 27 prostate cancer patients of Asian and Caucasian ethnicity, 18 of whom used CAM and 9 of whom did not. Using qualitative research methods, they examined perceptions of conventional medicine and CAM and contrasted viewpoints of CAM users and nonusers. Based on the patients' statements, the authors developed a model representing the viewpoints and thought patterns of CAM users as contrasted with those patients who did not use CAM. RESULTS: The interviews revealed notable differences in viewpoints between CAM users and nonusers in 4 areas. The following themes that were important to CAM users emerged from the analysis: a view of CAM as safe and holistic coupled with a view of conventional medicine as an aggressive and isolated treatment; concern about side effects, in particular, impotence and incontinence from conventional cancer therapy; a belief in the potential efficacy of CAM despite the lack of evidence; and a need to gain a sense of control. Although nonusers expressed similar concerns about side effects of conventional treatment and considered CAM harmless, they assigned different priorities to these issues in their decision making. CONCLUSIONS: In this study, no single theme was solely responsible for CAM use among prostate cancer patients. Instead, multiple ideas woven together led patients toward CAM use. An understanding of patients' thought processes may aid health care professionals in initiating a dialogue about decision making and potential side effects.

Religious and spiritual resources, CAM, and conventional treatment in the lives of cancer patients.

CONTEXT: In addition to seeking conventional treatment from physicians, cancer patients will often use religious and spiritual resources (RSR) and complementary and alternative medicine (CAM). Patients' beliefs about the relationships among RSR, CAM, and conventional treatments may reflect belief systems not readily apparent to physicians. OBJECTIVE: 1) Identify the RSR used and explore themes in beliefs regarding RSR, CAM, and conventional treatment. 2) Investigate the nature of the relationships among RSR, CAM, and conventional treatment in the lives of cancer patients. DESIGN: Cancer patients in Hawaii were recruited from a group who had previously completed a questionnaire on CAM use. In-depth interviews were conducted with a selected subset of survey participants. PARTICIPANTS: 143 cancer patients were interviewed 2 to 3 years following diagnosis. RESULTS: Participants reported using a variety of RSR, including personal faith, individual (self) prayer, relationship/dialog with God, prayers from fellow church members and others, counseling from pastor/priest or leader of faith, reading the bible, attending religious services, meditation, finding and spending time at locations of spiritual energy (i.e., churches, specific geographical locations, or certain natural settings), and help or counseling by ancestor(s). They also expressed beliefs that RSR, CAM, and conventional treatment have both shared and distinct purposes. RSR themes included providing treatment or cure, supporting treatment or cure, and being part of life. CAM themes included providing treatment or cure, supporting treatment or cure, preventing cancer and recurrence, substitution for conventional treatment, and as a last resort. Participants believed the purposes of conventional treatment were to fight/cure cancer and to improve quality of life. CONCLUSIONS: RSR, CAM, and conventional treatment served both spiritual and physical purposes. When participants perceived a relationship between RSR, CAM, and conventional treatment, it reflected shared spiritual and physical purposes. Such associations were especially strong when RSR, CAM, and conventional treatment shared the common goals of providing treatment or cure and/or supporting treatment or cure. Perceptions of shared purpose were individual to each participant, with religious congruence and life history playing a role in beliefs about the relationship between RSR and CAM. Such beliefs can affect issues of control, spiritual well-being, coping, depression, decision-making, and possibly health outcomes in cancer patients. Therefore, they should be addressed by clinicians in discussions with their patients.

Ethnic differences in choices of health information by cancer patients using complementary and alternative medicine: an exploratory study with correspondence analysis.

This study examined patterns in the use of health information among Caucasian, Japanese, and non-Japanese Asian Pacific Islander cancer patients in Hawaii and explored the relation of ethnicity and educational level to choices of health information sources. Information from 140 cancer patients, most of whom were users of complementary and alternative medicine (CAM), was analyzed using correspondence analysis. Three clusters of health information pertinent to the three ethnic groups emerged from the data. The results of this study revealed that Caucasian patients preferred objective, scientific, and updated information obtained through medical journals or newsletters from research institutions, telephone information services, and the internet. Japanese patients relied on media and commercial sources including television, newspapers, books, magazines and CAM providers. Non-Japanese Asians and Pacific Islanders used information sources involving person-to-person communication with their physicians, social groups, and other cancer patients. A higher educational level was closely related to a cluster of health information stressing objective, scientific and updated information, while a lower educational level was associated with interpersonally communicated information. The three ethnicity-specific patterns of health information use remained relatively stable at different educational levels, implying that the effect of patients' ethnicity overrides their educational level in shaping their choices of health information. The results of this study indicate the importance of recognizing cancer patients' culturally developed world views when understanding their health information-seeking behavior. For medical practice, these findings indicate the need for healthcare providers to assist cancer patients to obtain accurate health information in a culturally sensitive way.

Determinants of the degree of complementary and alternative medicine use among patients with cancer.

OBJECTIVES: This study explored the use of complementary and alternative medicine (CAM) by degree of use (nonuse, light, moderate, and heavy) by patients with cancer as it relates to sociodemographic and disease characteristics, subjective well-being, and dissatisfaction with the health care system. DESIGN AND PARTICIPANTS: One hundred and forty-three (143) patients with cancer of Asian, Caucasian, and Pacific Islander ethnicities originally recruited through the state-wide population-based Hawaii Tumor Registry and interviewed approximately 3 years postdiagnosis. OUTCOME MEASURES: This study introduced a multidimensional measure, degree of CAM use, to rank participants by quantity of CAMs used as well as frequency, intensity, and breadth of use. Predictor variables explored were sociodemographic variables, disease site, quality-of-life measures, satisfaction with conventional treatment and physicians, satisfaction with medical information, and perceived severity of illness. RESULTS: Heavier CAM use was related to being female, Caucasian, having more education, having breast cancer, and having greater symptoms of nausea and vomiting. Heavier use was also associated with lower doctor satisfaction and a greater perception of disease severity. Sociodemographic and clinical variables accounted for the largest proportion of the variance in degree of use, but subjective well-being and health care satisfaction provided incremental increases in the variance explained. CONCLUSIONS: This study is one of few studies exploring predictors for the quantity or degree of use of CAM by patients with cancer. Understanding factors related to these patients' heavier or lighter CAM use has implications for health care offerings and cancer treatment decision-making.

Communication between physicians and cancer patients about complementary and alternative medicine: exploring patients' perspectives.

The aim of this paper is to identify barriers to communication between physicians and cancer patients regarding complementary and alternative medicine (CAM) by exploring the perspectives of patients. In face of the recent popularity of CAM use among cancer patients, the lack of communication is a serious problem. A number of CAM therapies may interfere with conventional treatments and thus impact patients' well-being and chances of survival. In addition, lack of communication is problematic in the health care context because the development of openness and trust between health care providers and clients is contingent upon effective interpersonal communication. We conducted semi-structured interviews with 143 cancer patients to explore their experiences with CAM use. Using a qualitative research method, we examined interview data from 93 CAM users who provided sufficient information about communication issues. As a result, three themes emerged describing barriers to unsuccessful communication as perceived from the patient's point of view: physicians' indifference or opposition toward CAM use, physicians' emphasis on scientific evidence, and patients' anticipation of a negative response from their physician. Increasing education about CAM and regular assessment of CAM use may help physicians to be more aware of their patients' CAM use. As a result, physicians may provide patients with information on risks and benefits of CAM use and refer patients to other services that may address unmet needs. Given a difference in epistemiologic beliefs about cancer and its treatment, the challenge is to find a common ground for an open discussion in which physicians consider that scientific evidence is not all that counts in the life of an individual facing a serious disease.

A randomized isoflavone intervention among premenopausal women.

Isoflavones, phytoestrogens contained in soy foods, may play a role in breast cancer prevention. This randomized double-blinded trial with 34 premenopausal women investigated whether 100 mg of isoflavones per day versus placebo affects the ovulatory cycle during 1 year. Compliance with the study regimen was confirmed by the increase of urinary isoflavone excretion among the intervention group. Blood samples were taken 5 days after ovulation as determined by an ovulation kit, at baseline, and at months 1, 3, 6, and 12. Serum levels of estrone, estradiol, estrone sulfate, progesterone, sex hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone were quantified by immunoassay; free estradiol was calculated. We applied the method of least squares to fit general linear models to test for an intervention effect while taking into account the repeated measurement design. Except for a small difference in age, the two groups were comparable at baseline. Menstrual cycle length did not change significantly during the intervention [F(1,32) = 0.69; P = 0.44]. During 1 year, we did not observe any significant changes in hormone levels by treatment group. The difference in change between intervention and control group was -13.0 pg/ml (95% confidence interval, -57.5 to 31.5) for estradiol and 6.9 pg/ml (95% confidence interval, -17.8 to 31.5) for estrone. Exclusion of 22 non-ovulatory cycles, noncompliant women, or non-Asian women did not affect the results. These findings do not support the hypothesis that isoflavones affect the ovulatory cycles of premenopausal women over a 1-year period. However, isoflavones alone may have different effects on the reproductive cycle than isoflavones present in soy foods.