Neighborhood attributes and cardiovascular disease risk in breast cancer survivors: The Pathways Study.

BACKGROUND: Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined. METHODS: The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California. Women diagnosed with breast cancer from 2006 through 2013 were enrolled on average approximately 2 months after diagnosis. Their baseline addresses were geocoded and appended to neighborhood attributes for racial/ethnic composition, socioeconomic status (SES), population density, urbanization, crime, traffic density, street connectivity, parks, recreational facilities, and retail food environment. Incident CVD events included ischemic heart disease, heart failure, cardiomyopathy, or stroke. Cox proportional hazards models estimated associations of neighborhood attributes with CVD risk, which accounted for clustering by block groups. Fully adjusted models included sociodemographic, clinical, and behavioral factors. RESULTS: During follow-up through December 31, 2018, 340 participants (8.6%) had CVD events. A neighborhood racial/ethnic composition measure, percent of Asian American/Pacific Islander residents (lowest quintile hazard ratio [HR], 1.85; 95% CI, 1.03-3.33), and crime index (highest quartile HR, 1.48; 95% CI, 1.08-2.03) were associated with the risk of CVD events independent of individual SES, hormone receptor status, treatment, cardiometabolic comorbidities, body mass index, and physical activity. CONCLUSIONS: With the application of a socio-ecological framework, how residential environments shape health outcomes in women with breast cancer and affect CVD risk in this growing population can be understood.

Traffic-related Air Pollution and Lung Cancer Incidence: The California Multiethnic Cohort Study.

Rationale: Although the contribution of air pollution to lung cancer risk is well characterized, few studies have been conducted in racially, ethnically, and socioeconomically diverse populations. Objectives: To examine the association between traffic-related air pollution and risk of lung cancer in a racially, ethnically, and socioeconomically diverse cohort. Methods: Among 97,288 California participants of the Multiethnic Cohort Study, we used Cox proportional hazards regression to examine associations between time-varying traffic-related air pollutants (gaseous and particulate matter pollutants and regional benzene) and lung cancer risk (n = 2,796 cases; average follow-up = 17 yr), adjusting for demographics, lifetime smoking, occupation, neighborhood socioeconomic status (nSES), and lifestyle factors. Subgroup analyses were conducted for race, ethnicity, nSES, and other factors. Measurements and Main Results: Among all participants, lung cancer risk was positively associated with nitrogen oxide (hazard ratio [HR], 1.15 per 50 ppb; 95% confidence interval [CI], 0.99-1.33), nitrogen dioxide (HR, 1.12 per 20 ppb; 95% CI, 0.95-1.32), fine particulate matter with aerodynamic diameter <2.5 µm (HR, 1.20 per 10 µg/m3; 95% CI, 1.01-1.43), carbon monoxide (HR, 1.29 per 1,000 ppb; 95% CI, 0.99-1.67), and regional benzene (HR, 1.17 per 1 ppb; 95% CI, 1.02-1.34) exposures. These patterns of associations were driven by associations among African American and Latino American groups. There was no formal evidence for heterogeneity of effects by nSES (P heterogeneity > 0.21), although participants residing in low-SES neighborhoods had increased lung cancer risk associated with nitrogen oxides, and no association was observed among those in high-SES neighborhoods. Conclusions: These findings in a large multiethnic population reflect an association between lung cancer and the mixture of traffic-related air pollution and not a particular individual pollutant. They are consistent with the adverse effects of air pollution that have been described in less racially, ethnically, and socioeconomically diverse populations. Our results also suggest an increased risk of lung cancer among those residing in low-SES neighborhoods.

Urinary phthalate exposures and risk of breast cancer: the Multiethnic Cohort study.

BACKGROUND: The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women. METHODS: We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHMmolar) and adjusted for creatinine and potential confounders. RESULTS: Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04-1.68) and 1.26 (95% CI 0.96-1.66) (Ptrend = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA ORT3 vs T1 = 2.66, 95% CI 1.39-5.12, Ptrend = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05-1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (ORabove vs below median = 1.59, 95% CI 1.01-2.48). CONCLUSIONS: Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.

Risk of breast cancer and prediagnostic urinary excretion of bisphenol A, triclosan and parabens: The Multiethnic Cohort Study.

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case-control study investigated endocrine-disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (Ptrend  = 0.53) and was inversely associated with triclosan (ORT3 vs T1  = 0.83, 95% CI: 0.66-1.04, Ptrend  = 0.045) and total parabens (ORT3 vs T1  = 0.77, 95% CI: 0.62-0.97, Ptrend  = 0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (Ptrend  = 0.02), risk of HR negative (HR-) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (ORT3 vs T1  = 0.76, 95% CI: 0.56-1.02, Ptrend  = 0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk.

Association between ambient air pollution and breast cancer risk: The multiethnic cohort study.

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NOx , NO2 , PM10 , PM2.5 ), land use regression (LUR, NOx , NO2 ) and California Line Source Dispersion model (CALINE4, NOx , PM2.5 ) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993-1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NOx (per 50 parts per billion [ppb]) and NO2 (per 20 ppb) determined by kriging and LUR and with PM2.5 and PM10 (per 10 µg/m3 ) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NOx (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02-1.79), NO2 (HR = 1.44, 95% CI: 1.04-1.99), PM10 (HR = 1.29, 95% CI: 1.07-1.55) and PM2.5 (HR = 1.85, 95% CI: 1.15-2.99) determined by kriging and NOx (HR = 1.21, 95% CI:1.01-1.45) and NO2 (HR = 1.26, 95% CI: 1.00-1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NOx and NO2 among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.

Racial and Ethnic Disparities in Human Milk Intake at Neonatal Intensive Care Unit Discharge among Very Low Birth Weight Infants in California.

OBJECTIVES: To examine how infant and maternal factors, hospital factors, and neighborhood-level factors impact or modify racial/ethnic disparities in human milk intake at hospital discharge among very low birth weight infants. STUDY DESIGN: We studied 14 422 infants from 119 California Perinatal Quality Care Collaborative neonatal intensive care units born from 2008 to 2011. Maternal addresses were linked to 2010 census tract data, representing neighborhoods. We tested for associations with receiving no human milk at discharge, using multilevel cross-classified models. RESULTS: Compared with non-Hispanic whites, the adjusted odds of no human milk at discharge was higher among non-Hispanic blacks (aOR 1.33 [1.16-1.53]) and lower among Hispanics (aOR 0.83 [0.74-0.93]). Compared with infants of more educated white mothers, infants of less educated white, black, and Asian mothers had higher odds of no human milk at discharge, and infants of Hispanic mothers of all educational levels had similar odds as infants of more educated white mothers. Country of birth and neighborhood socioeconomic was also associated with disparities in human milk intake at discharge. CONCLUSIONS: Non-Hispanic blacks had the highest and Hispanic infants the lowest odds of no human milk at discharge. Maternal education and country of birth were the biggest drivers of disparities in human milk intake, suggesting the need for targeted approaches of breastfeeding support.

Type 2 diabetes as a predictor of survival among breast cancer patients: the multiethnic cohort.

PURPOSE: The purpose of the study was to investigate the association of type 2 diabetes (T2D) with survival of breast cancer (BC) patients across five ethnic groups within the Multiethnic Cohort study. METHODS: Between recruitment in 1993-1996 and 2013, 7570 incident BC cases were identified through SEER cancer registries in Hawaii and California. T2D diagnosed before BC was ascertained in 1013 women from self-reports and confirmed by administrative data sources. Covariate information was collected by questionnaire. Cox regression analysis with age as the time metric and BMI as time-varying exposure was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BC-specific and all-cause survival while adjusting for known prognostic factors. RESULTS: In total, 2119 all-cause and 730 BC-specific deaths were recorded with corresponding 5-year survival rates of 86 and 93%. T2D was not a significant predictor of BC-specific survival (HR 0.84; 95% CI 0.65-1.09), but mortality was 36% lower for those with < 7 years of T2D than a longer history of T2D. On the other hand, all-cause mortality was higher in women with T2D (HR 1.23; 95% CI 1.08-1.40), especially in women with T2D of ≥ 7 years duration (HR 1.27; 95% CI 1.07-1.49). In women receiving none or either chemotherapy or radiation but not both, T2D predicted higher all-cause mortality (Pinteraction = 0.004). Variations in the association of T2D with mortality across ethnic groups were small. CONCLUSIONS: T2D was associated with higher all-cause but not BC-specific mortality among women with BC in the Multiethnic Cohort study. However, T2D affected survival in cases who did not receive both radiation and chemotherapy.

Characterizing the neighborhood obesogenic environment in the Multiethnic Cohort: a multi-level infrastructure for cancer health disparities research.

PURPOSE: We characterized the neighborhood obesogenic environment in the Multiethnic Cohort (MEC) by examining the associations of obesity with attributes of the social and built environment, establishing a multi-level infrastructure for future cancer research. METHODS: For 102,906 African American, Japanese American, Latino, and white MEC participants residing predominately in Los Angeles County, baseline residential addresses (1993-1996) were linked to census and geospatial data, capturing neighborhood socioeconomic status (nSES), population density, commuting, food outlets, amenities, walkability, and traffic density. We examined neighborhood attributes and obesity (body mass index ≥ 30 kg/m2) associations using multinomial logistic regression, adjusting for individual-level (e.g., demographics, physical activity, and diet) and neighborhood-level factors. RESULTS: NSES was associated with obesity among African Americans, Latinos, and whites (p-trend ≤ 0.02), with twofold higher odds (adjusted odds ratios, 95% confidence intervals) for living in the lowest versus highest quintile among African American women (2.07, 1.62-2.65), white men (2.11, 1.29-3.44), and white women (2.50, 1.73-3.61). Lower density of businesses among African American and white women and lower traffic density among white men were also associated with obesity (p-trends ≤ 0.02). CONCLUSIONS: Our study highlights differential impacts of neighborhood factors across racial/ethnic groups and establishes the foundation for multi-level studies of the neighborhood context and obesity-related cancers.

Mammographic density and breast cancer risk by family history in women of white and Asian ancestry.

PURPOSE: Mammographic density, i.e., the radiographic appearance of the breast, is a strong predictor of breast cancer risk. To determine whether the association of breast density with breast cancer is modified by a first-degree family history of breast cancer (FHBC) in women of white and Asian ancestry, we analyzed data from four case-control studies conducted in the USA and Japan. METHODS: The study population included 1,699 breast cancer cases and 2,422 controls, of whom 45% reported white (N = 1,849) and 40% Asian (N = 1,633) ancestry. To standardize mammographic density assessment, a single observer re-read all mammograms using one type of interactive thresholding software. Logistic regression was applied to estimate odds ratios (OR) while adjusting for confounders. RESULTS: Overall, 496 (12%) of participants reported a FHBC, which was significantly associated with breast cancer risk in the adjusted model (OR 1.51; 95% CI 1.23-1.84). There was a statistically significant interaction on a multiplicative scale between FHBC and continuous percent density (per 10 % density: p = 0.03). The OR per 10% increase in percent density was higher among women with a FHBC (OR 1.30; 95% CI 1.13-1.49) than among those without a FHBC (OR 1.14; 1.09-1.20). This pattern was apparent in whites and Asians. The respective ORs were 1.45 (95% CI 1.17-1.80) versus 1.22 (95% CI 1.14-1.32) in whites, whereas the values in Asians were only 1.24 (95% CI 0.97-1.58) versus 1.09 (95% CI 1.00-1.19). CONCLUSIONS: These findings support the hypothesis that women with a FHBC appear to have a higher risk of breast cancer associated with percent mammographic density than women without a FHBC.

Methods for assessing and representing mammographic density: an analysis of 4 case-control studies.

To maximize statistical power in studies of mammographic density and breast cancer, it is advantageous to combine data from several studies, but standardization of the density assessment is desirable. Using data from 4 case-control studies, we describe the process of reassessment and the resulting correlation between values, identify predictors of differences in density readings, and evaluate the strength of the association between mammographic density and breast cancer risk using different representations of density values. The pooled analysis included 1,699 cases and 2,422 controls from California (1990-1998), Hawaii (1996-2003), Minnesota (1992-2001), and Japan (1999-2003). In 2010, a single reader reassessed all images for mammographic density using Cumulus software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean difference between original and reassessed percent density values was -0.7% (95% confidence interval: -1.1, -0.3), with a correlation of 0.82 that varied by location (r = 0.80-0.89). Case status, weight status, age, parity, density assessment method, mammogram view, and race/ethnicity were significant determinants of the difference between original and reassessed values; in combination, these factors explained 9.2% of the variation. The associations of mammographic density with breast cancer and the model fits were similar using the original values and the reassessed values but were slightly strengthened when a calibrated value based on 100 reassessed radiographs was used.

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort.

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for ß-carotene. Other carotenoids, including α-carotene, ß-carotene, lutein, ß-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.

Mammographic density as a predictor of breast cancer survival: the Multiethnic Cohort.

INTRODUCTION: Mammographic density, a strong predictor for breast cancer incidence, may also worsen prognosis in women with breast cancer. This prospective analysis explored the effect of prediagnostic mammographic density among 607 breast cancer cases diagnosed within the Hawaii component of the Multiethnic Cohort (MEC). METHODS: Female MEC participants, aged ≥ 50 years at cohort entry, diagnosed with primary invasive breast cancer, and enrolled in a mammographic density case-control study were part of this analysis. At cohort entry, anthropometric and demographic information was collected by questionnaire. Tumor characteristics and vital status were available through linkage with the Hawaii Tumor Registry. Multiple digitized prediagnostic mammograms were assessed for mammographic density using a computer-assisted method. Cox proportional hazards regression was applied to examine the effect of mammographic density on breast cancer survival while adjusting for relevant covariates. RESULTS: Of the 607 cases, 125 were diagnosed as in situ, 380 as localized, and 100 as regional/distant stage. After a mean follow-up time of 12.9 years, 27 deaths from breast cancer and 100 deaths from other causes had occurred; 71 second breast cancer primaries were diagnosed. In an overall model, mammographic density was not associated with breast cancer-specific survival (HR = 0.95 per 10%; 95%CI: 0.79-1.15), but the interaction with radiotherapy was highly significant (p = 0.006). In stratified models, percent density was associated with a reduced risk of dying from breast cancer (HR = 0.77; 95%CI: 0.60-0.99; p = 0.04) in women who had received radiation, but with an elevated risk (HR = 1.46; 95% CI: 1.00-2.14; p = 0.05) in patients who had not received radiation. High breast density predicted a borderline increase in risk for a second primary (HR = 1.72; 95% CI: 0.88-2.55; p = 0.15). CONCLUSIONS: Assessing mammographic density in women with breast cancer may identify women with a poorer prognosis and provide them with radiotherapy to improve outcomes.

The effects of soy consumption before diagnosis on breast cancer survival: the Multiethnic Cohort Study.

This study tested the hypothesis that prediagnostic soy intake was inversely associated with all-cause and breast cancer-specific mortality. The analyses included 3842 women in the Multiethnic Cohort (MEC) study of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians, who completed a quantitative food frequency questionnaire, aged ≥50 yr at cohort entry, and diagnosed with primary invasive breast cancer following cohort entry (1993-2007). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from Cox proportional hazards regression with adjustment for known clinical and lifestyle factors. During a mean follow-up after diagnosis of invasive breast cancer of 6.2 ± 3.8 yr, there were 804 deaths including 376 breast cancer-specific deaths. The HR (95%CI) for all-cause and breast cancer-specific morality comparing the highest versus lowest tertiles were 1.03 (0.81-1.33) and 1.03 (0.71-1.50) for soy products and 0.99 (0.82-1.20) and 0.95 (0.71-1.28) for total isoflavones, respectively (Ptrend > 0.60 for all). There was limited evidence of differences by hormone receptor status, tumor stage, or ethnic group. Prediagnostic soy intake was unrelated to mortality in postmenopausal women. Our findings are consistent with the literature that soy consumption does not adversely affect breast cancer survival in women.

Mammographic density and risk of breast cancer by adiposity: an analysis of four case-control studies.

The association of mammographic breast density with breast cancer risk may vary by adiposity. To examine effect modification by body mass index (BMI), the authors standardized mammographic density data from four case-control studies (1994-2002) conducted in California, Hawaii and Minnesota and Gifu, Japan. The 1,699 cases and 2,422 controls included 45% Caucasians, 40% Asians and 9% African-Americans. Using ethnic-specific BMI cut points, 34% were classified as overweight and 19% as obese. A single reader assessed density from mammographic images using a computer-assisted method. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. Modest heterogeneity in the relation between percent density and breast cancer risk across studies was observed (p(heterogeneity) = 0.08). Cases had a greater age-adjusted mean percent density than controls: 31.7% versus 28.5%, respectively (p <0.001). Relative to <20 percent density, the ORs for >35 were similar across BMI groups whereas the OR for 20-35 was slightly higher in overweight (OR = 1.69, 95% CI: 1.28, 2.24) and obese (OR = 1.62, 95% CI: 1.12, 2.33) than in normal weight women (OR = 1.49, 95% CI: 1.11, 2.01). Furthermore, limited evidence of effect modification by BMI of the OR per 10% increase in percent density (p(interaction) = 0.06) was observed, including subgroup analyses by menopausal status and in analyses that excluded women at the extremes of the BMI scale. Our findings indicate little, if any, modification by BMI of the effects of breast density on breast cancer risk.

Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case-control studies.

Mammographic density is strongly and consistently associated with breast cancer risk. To determine if this association was modified by reproductive factors (parity and age at first birth), data were combined from four case-control studies conducted in the United States and Japan. To overcome the issue of variation in mammographic density assessment among the studies, a single observer re-read all the mammograms using one type of interactive thresholding software. Logistic regression was used to estimate odds ratios (OR) while adjusting for other known breast cancer risk factors. Included were 1,699 breast cancer cases and 2,422 controls, 74% of whom were postmenopausal. A positive association between mammographic density and breast cancer risk was evident in every group defined by parity and age at first birth (OR per doubling of percent mammographic density ranged between 1.20 and 1.39). Nonetheless, the association appeared to be stronger among nulliparous than parous women (OR per doubling of percent mammographic density = 1.39 vs. 1.24; P interaction = 0.054). However, when examined by study location, the effect modification by parity was apparent only in women from Hawaii and when examined by menopausal status, it was apparent in postmenopausal, but not premenopausal, women. Effect modification by parity was not significant in subgroups defined by body mass index or ethnicity. Adjusting for mammographic density did not attenuate the OR for the association between parity and breast cancer risk by more than 16.4%, suggesting that mammographic density explains only a small proportion of the reduction in breast cancer risk associated with parity. In conclusion, this study did not support the hypothesis that parity modifies the breast cancer risk attributed to mammographic density. Even though an effect modification was found in Hawaiian women, no such thing was found in women from the other three locations.

Erythrocyte membrane fatty acid composition, serum lipids, and non-Hodgkin's lymphoma risk in a nested case-control study: the multiethnic cohort.

PURPOSE: Composition of dietary fatty acid intake, which influences cytokine production, may contribute to the development of non-Hodgkin's lymphoma (NHL). Serum lipid levels may serve as biomarkers of inflammation associated with NHL risk. METHODS: We conducted a case-control analysis (275 cases and 549 controls) nested within the Multiethnic Cohort Study (whites, Japanese Americans, Latinos, African Americans, and Native Hawaiians) to examine the association of prediagnostic, erythrocyte membrane phospholipid fatty acid composition, and serum cholesterol and triglyceride (TG) concentrations with the risk of NHL. Conditional logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) by tertiles of biomarker concentrations. RESULTS: Higher total saturated fatty acids (SFA) were associated with an increase in NHL risk (OR(T3 vs. T1) = 1.57 [95 % CI: 1.03-2.39]; p(trend) = 0.01), whereas no associations were detected for total n-3 or n-6 polyunsaturated fatty acids. Inverse associations were observed for total cholesterol (TC; OR (T3 vs. T1) = 0.51 [95 % CI: 0.35-0.74]; p(trend) < 0.0001) and high-density lipoprotein cholesterol (HDL-C; OR (T3 vs. T1) = 0.47 [95 % CI: 0.31-0.71]; p(trend) = 0.0001) but not for low-density lipoprotein cholesterol or TG. Adjustment for the use of lipid-lowering medication did not modify the results substantially. CONCLUSIONS: This prospective biomarker investigation offers supportive evidence for an adverse effect of higher erythrocyte membrane SFA levels on NHL risk, but preclinical effects cannot be excluded. Inverse relations between prediagnostic, circulating TC and HDL-C and NHL risk may be due to reverse causation or a result of protective actions of these lipids and lipoproteins.

Urinary estrogen metabolites during a randomized soy trial.

One of the hypothesized protective mechanisms of soy against breast cancer involves changes in estrogen metabolism to 2-hydroxy (OH) and 16α-OH estrogens. The current analysis examined the effect of soy foods on the 2:16α-OH E(1) ratio among premenopausal women during a randomized, crossover intervention study; women were stratified by equol producer status, a characteristic thought to enhance the protective effects of soy isoflavones. The study consisted of a high-soy diet with 2 soy food servings/day and a low-soy diet with <3 servings of soy/wk for 6 mo each; estrogen metabolites were measured in 3 overnight urines (baseline and at the end of the low- and high-soy diet) using gas chromatography mass spectrometry for the 82 women who completed the study. Urinary isoflavonoids were assessed by liquid chromatography mass spectrometry. When applying mixed models, the 2:16α-OH E(1) ratio increased (P = 0.05) because of a nonsignificant decrease in 16α-OH E(1) (P = 0.21) at the end of the high-soy diet. Similar nonsignificant increases in the 2:16α-OH E(1) ratio were observed in equol producers (P = 0.13) and nonproducers (P = 0.23). These findings suggest a beneficial influence of soy foods on estrogen metabolism regardless of equol producer status.

Asian ethnicity is associated with a higher trunk/peripheral fat ratio in women and adolescent girls.

BACKGROUND: Ethnic differences in body fat mass and distribution may develop in childhood and contribute to increased obesity-related disease risk among Asians. We used dual-energy X-ray absorptiometry (DXA) to evaluate adiposity measures among adult women and their adolescent daughters, who were of predominantly Japanese and white ethnicity. METHODS: We obtained DXA whole body scans for 101 mothers aged 30 years or older and 112 daughters aged 10 to 16 years. The participants were classified as Asian, part-Asian, mixed/other, or white. As a measure of central adiposity, we calculated the trunk/peripheral fat ratio (TPFR). General linear models were used to evaluate differences in adiposity measures by ethnic category. RESULTS: In mothers, TPFR was significantly higher (P(trend) < 0.01) in Asians and part-Asians (1.38 ± 0.42 and 1.32 ± 0.51) than in mixed/others and whites (1.18 ± 0.27 and 1.09 ± 0.21). The trend was similar among daughters (P(trend) < 0.001), with respective values of 1.09 ± 0.18, 0.97 ± 0.17, 0.99 ± 0.16, and 0.87 ± 0.11. Among mothers, gynoid fat mass and peripheral fat mass were significantly lower in Asians than in whites, whereas none of the regional DXA adiposity measures differed by ethnicity in daughters. CONCLUSIONS: These results confirm previous reports of greater central adiposity in women of Asian ancestry and indicate that ethnic differences in adiposity are already present in adolescence.

Joint Associations of Race, Ethnicity, and Socioeconomic Status With Mortality in the Multiethnic Cohort Study.

Importance: Socioeconomic status may help delineate racial and ethnic inequities in mortality. Objective: To investigate the joint associations of race, ethnicity, and neighborhood and individual socioeconomic status with mortality. Design, Setting, and Participants: This prospective analysis used data from the Multiethnic Cohort Study. A population-based sample of participants recruited from California (mainly Los Angeles County) and Hawaii from 1993 to 1996 was followed up until 2013. African American, European American, Japanese American, Latino American, and Native Hawaiian men and women were included. Participants with baseline residential addresses that could not be geocoded or who were missing information on education or adjustment variables were excluded. Data analyses were conducted from January 2018 to December 2020. Exposures: Neighborhood socioeconomic status (nSES) was derived using US Census block group data on education, occupation, unemployment, household income, poverty, rent, and house values. Participants self-reported their highest education attainment. Five racial and ethnic groups, 2 states of residence, 2 nSES, and 2 education categories were combined to create a joint exposure variable. Low and high nSES were defined as quintiles 1 to 3 and 4 to 5, respectively. Low and high education levels were defined as high school or less and greater than high school graduate, respectively. Main Outcomes and Measures: All-cause, cardiovascular disease (CVD), cancer, and non-CVD and noncancer deaths were ascertained through 2013 via linkage to death certificates and the US National Death Index. Multivariable Cox proportional hazards regression analyses were conducted. Results: Among 182 912 participants (100 785 [55.1%] women and 82 127 [44.9%] men; mean [SD] age, 60.0 [8.9] years; 31 138 African American, 45 796 European American, 52 993 Japanese American, 39 844 Latino American, and 13 141 Native Hawaiian participants) with a mean (SD) follow-up of 17 (5) years, there were 63 799 total deaths, including 23 191 CVD deaths, 19 008 cancer deaths, and 21 235 non-CVD and noncancer deaths. The lowest all-cause mortality was found among 15 104 Japanese American participants in Hawaii with high nSES and high education (eg, 2870 all-cause deaths [19.0%]), and this population served as the reference group for all regression analyses. Native Hawaiian participants in Hawaii with low nSES and low education had the highest all-cause mortality HR (2.38; 95% CI, 2.21-2.57). African American and European American participants in California with low nSES and low education had the next highest all-cause mortality HRs (2.01; 95% CI, 1.91-2.11 and 1.98; 95% CI, 1.85-2.12, respectively). Latino American participants in California with low nSES had equivalent all-cause mortality HRs regardless of education level (high education: 1.57; 95% CI, 1.48-1.66; low education: 1.57; 95% CI, 1.50-1.65). Patterns for cause-specific mortality were similar to those for all-cause mortality. For example, Native Hawaiian participants in Hawaii with low nSES and low education had highest CVD mortality HR (2.92; 95% CI, 2.60-3.27) and cancer mortality HR (2.01; 95% CI, 1.77-2.29). Conclusions and Relevance: These results suggest that joint associations of nSES and education may further delineate racial and ethnic inequities in mortality and that future investigations of racial and ethnic inequities in mortality should consider differences by measures of socioeconomic status, especially for underserved populations.

Outdoor ambient air pollution and breast cancer survival among California participants of the Multiethnic Cohort Study.

BACKGROUND: Within the Multiethnic Cohort (MEC), we examined the association between air pollution and mortality among African American, European American, Japanese American, and Latina American women diagnosed with breast cancer. METHODS: We used a land use regression (LUR) model and kriging interpolation to estimate nitrogen oxides (NOx , NO2) and particulate matter (PM2.5, PM10) exposures for 3,089 breast cancer cases in the MEC, who were diagnosed from 1993 through 2013 and resided largely in Los Angeles County, California. Cox proportional hazards models were used to examine the association of time-varying air pollutants with all-cause, breast cancer, cardiovascular disease (CVD), and non-breast cancer/non-CVD mortality, accounting for key covariates. RESULTS: We identified 1,125 deaths from all causes (474 breast cancer, 272 CVD, 379 non-breast cancer/non-CVD deaths) among the 3,089 breast cancer cases with 8.1 years of average follow-up. LUR and kriged NOX (per 50 ppb) and NO2 (per 20 ppb), PM2.5 (per 10 µg/m3), and PM10 (per 10 µg/m3) were positively associated with risks of all-cause (Hazard Ratio (HR) range = 1.13-1.25), breast cancer (HR range = 1.19-1.45), and CVD mortality (HR range = 1.37-1.60). Associations were statistically significant for LUR NOX and CVD mortality (HR = 1.60; 95% CI: 1.08-2.37) and kriged NO2 and breast cancer mortality (HR = 1.45; 95% CI 1.02-2.07). Gaseous and PM pollutants were positively associated with breast cancer mortality across racial/ethnic group. CONCLUSION: In this study, air pollutants have a harmful impact on breast cancer survival. Additional studies should evaluate potential confounding by socioeconomic factors. These data support maintaining clean air laws to improve survival for women with breast cancer.