Dietary Vitamin A and Breast Cancer Risk in Black Women: The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

BACKGROUND: Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. OBJECTIVES: We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. METHODS: In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. RESULTS: We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67-1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43-0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77-1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary ß-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51-0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45-0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. CONCLUSIONS: Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations. METHODS: We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels. RESULTS: Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments. CONCLUSIONS: Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether pre-diagnostic lipid levels are associated with Amyotrophic lateral sclerosis (ALS) risk. Methods: We conducted a matched case-control study nested in five large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the Women's Health Initiative), and identified 275 individuals who developed ALS during follow-up and had provided blood samples before disease diagnosis. For each ALS case, we randomly selected two controls who were alive at the time of the case diagnosis and matched on cohort, birth year (±1 year), sex, race/ethnicity, fasting status, and time of blood draw. We measured total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels in the plasma samples, and used conditional logistic regression to estimate associations between lipid levels and ALS risk. Results: Higher levels of HDL-C were associated with higher ALS risk in an analysis adjusted for the matching factors (risk ratio [RR] Q4 vs. Q1: 1.78, 95% confidence interval [CI]: 1.18-2.69, p trend: 0.007). The estimate remained similar in a multivariable analysis additionally adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, and use of cholesterol-lowering drugs (RR Q4 vs. Q1: 1.71, 95% CI: 1.07-2.73, p trend: 0.02). Plasma levels of TC, LDL-C, and TG were not associated with ALS risk. Conclusions: Higher pre-diagnostic HDL-C levels, but not levels of other lipids, were associated with a higher risk of ALS.

Association of serum γ-tocopherol levels with mortality: the Multiethnic Cohort Study.

BACKGROUND/OBJECTIVES: γ-Tocopherol has unique properties that protect against nitrogen oxide-mediated cellular damage. To elucidate the potential role of γ-tocopherol in the aging process, we examined the associations of serum γ-tocopherol levels with all-cause and cause-specific mortality. SUBJECTS/METHODS: Among participants in the biorepository subcohort of the Multiethnic Cohort Study, pre-cancer diagnostic serum γ-tocopherol levels were measured in a subset of 3904 men and 4461 women. Of these, 22.7% of men and 13.5% of women died during a mean follow-up time of 9.6 ± 2.6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality associated with γ-tocopherol were estimated by Cox proportional hazards regression. RESULTS: Positive associations of serum γ-tocopherol with all-cause, cancer, and cardiovascular disease mortality (CVD) (Ptrend < 0.05) were detected after adjusting for age, race/ethnicity, and serum cholesterol levels. The respective HRs (95% CIs) for the highest versus the lowest sex-specific γ-tocopherol quartile were 1.43 (1.17-1.74), 1.79 (1.22-2.64), and 1.52 (1.10-2.11) for men and 1.58 (1.25-2.00), 1.59 (1.05-2.41), and 1.59 (1.07-2.37) for women. Associations remained significant for all-cause mortality among women after further adjusting for smoking variables and history of cancer, CVD, diabetes, and hypertension at cohort entry (highest vs. lowest γ-tocopherol quartile: HR = 1.38; 95% CI = 1.08-1.75; Ptrend = 0.005). Overall, associations with all-cause mortality were consistent across race/ethnicity and were significant in three of ten sex-specific racial/ethnic groups in the fully adjusted models, with no interactions between ethnicity and γ-tocopherol. CONCLUSIONS: The positive association between γ-tocopherol and mortality suggests a potential physiological role for γ-tocopherol in response to pathological conditions.

Intake of cocoa products and risk of type-2 diabetes: the multiethnic cohort.

BACKGROUND/OBJECTIVES: As cocoa products may be protective against chronic disease due to their polyphenol content, the current study determined the association of chocolate consumption and flavanol intake with type-2 diabetes (T2D) incidence in the Multiethnic Cohort (MEC) Study. SUBJECTS/METHODS: The analysis included 151,691 participants of Native Hawaiian, Japanese American, Latino, African American, and white ancestry with 8487 incident T2D cases after 7.8 ± 3.5 years of follow-up. T2D status was based on three self-reports and confirmed by at least one of three administrative data sources. Dietary intake was assessed using a validated quantitative food frequency questionnaire, and flavanols from cocoa products were estimated from self-reported consumption of chocolate candy and drinks. Cox hazard regression, adjusted for potential confounders was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: For chocolate candy, both the highest vs. lowest (≥10 vs. <1 g/day) consumption (HR = 0.90; 95% CI, 0.83-0.97; ptrend = 0.01) and the frequency (≥4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; ptrend = 0.0002) were inversely associated with T2D. The estimated flavanol intake from cocoa products (≥3 vs. <1 mg/day) also showed an inverse association with T2D risk (HR = 0.93; 95% CI, 0.88-0.99; ptrend = 0.02). Significant interaction terms indicated that the inverse relation was limited to Japanese Americans, normal-weight individuals, and to those without comorbidities. CONCLUSIONS: The current study confirms previous reports that participants with high intake of chocolate products and cocoa-derived flavanols experience a reduced risk of developing T2D even after controlling for sugar intake, diet quality, and other aspects of the diet.

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk. METHODS: We included participants from 5 large cohort studies-The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative-and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography-mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk. RESULTS: None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57-1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52-1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52-1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset. CONCLUSION: The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.

Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies.

BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort.

PURPOSE: To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes. METHODS: This analysis includes controls of case-control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor-α. RESULTS: Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (pinteraction = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw. CONCLUSION: The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.

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.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Dietary Red and Processed Meat Intake and Markers of Adiposity and Inflammation: The Multiethnic Cohort Study.

OBJECTIVE: The potential influence of dietary factors on inflammation is important for cancer prevention. Utilizing data from control participants (312 men, 911 women) in 2 nested case-control studies of cancer within the Multiethnic Cohort, we examined the associations of red and processed meat intake with serum levels of leptin, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and the mediator effect of body mass index (BMI) on the above associations (if present). METHODS: Multivariable linear models were applied to assess the association between red and processed meat intake at cohort entry and serum biomarker levels measured 9.1 years later after adjusting for covariates and to determine the mediator effect of BMI. RESULTS: Overall red and processed meat intake was positively associated with serum leptin levels in men (ß = 0.180, p = 0.0004) and women (ß = 0.167, p < 0.0001). In women, higher red and processed meat consumption was significantly associated with higher CRP (ß = 0.069, p = 0.03) and lower adiponectin levels (ß = -0.082, p = 0.005). In mediation analyses with red and processed meat intake and BMI as predictors, the associations of red and processed meat with biomarkers decreased substantially (as indicated by percentage change in effect: leptin in men, 13.4%; leptin in women, 13.7%; adiponectin in women, -4.7%; CRP in women, 7.4%) and were no longer significant (p > 0.05), whereas BMI remained significantly associated with serum leptin (men: ß = 3.209, p < 0.0001; women: ß = 2.891, p < 0.0001), adiponectin (women: ß = -1.085, p < 0.0001), and CRP (women: ß = 1.581, p < 0.0001). CONCLUSION: The current data suggest that the amount of excess body weight or the degree of adiposity may mediate the relations between dietary red and processed meat intake and serum biomarkers associated with obesity and inflammation.

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear.Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model.Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index.Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer.Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR.

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry.Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality.Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry.Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR.

Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium.

Background: Alcohol is a recognized risk factor for invasive breast cancer, but few studies involve African American women.Methods: The current analysis included 22,338 women (5,108 cases of invasive breast cancer) from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. The association between number of alcoholic drinks per week (dpw) and breast cancer was estimated using logistic regression, adjusting for potential confounders, and stratifying by breast cancer subtype.Results: Approximately 35% of controls were current drinkers at interview. Women who reported current drinking of ≥14 dpw had an elevated risk of breast cancer compared with light drinkers (>0-<4 dpw) [adjusted OR (ORadj), 1.33; 95% confidence interval (CI), 1.07-1.64]. We observed elevated risk among women drinking ≥7 dpw for ER - [ORadj, 1.31; 95% CI, 1.00-1.72], PR - [ORadj, 1.28; 95% CI, 1.00-1.63], HER2 - [ORadj, 1.36; 95% CI, 1.09-1.70], and triple-negative [ORadj, 1.39; 95% CI, 0.98-2.00] molecular subtype. Among receptor-positive cases, ORs remained elevated but attenuated relative to receptor-negative cases. Sensitivity analysis of age-defined windows of exposure (<30 years, 30-49, 50+ years of age) did not reveal variation in patterns of association. Risk associated with alcohol intake did not vary significantly by oral contraceptive use, smoking status, or menopausal status.Conclusions: Among African American women, similar to women of European descent, drinking ≥7 alcoholic dpw was associated with an increased risk of breast cancer regardless of subtype.Impact: Alcohol intake is a modifiable risk factor for breast cancer, and reduced intake among African American women should be encouraged. Cancer Epidemiol Biomarkers Prev; 26(5); 787-94. ©2017 AACR.

Contextual Impact of Neighborhood Obesogenic Factors on Postmenopausal Breast Cancer: The Multiethnic Cohort.

Background: While obesity is well-understood to increase breast cancer risk, the role of the neighborhood obesogenic environment, encompassing social and built environment attributes that influence body size, is poorly understood.Methods: Using principal components factor analysis, five composite factors [neighborhood socioeconomic status (nSES), urban, mixed-land development, unhealthy food environment, parks] on the basis of geospatial data were developed to characterize the obesogenic environment for 48,247 postmenopausal women in the Multiethnic Cohort, residing predominately in Los Angeles County. We used Cox proportional hazards regression to examine the association between neighborhood obesogenic factors and breast cancer risk (n = 2,341 cases after 17 years of follow-up), adjusting for body mass index (BMI), weight gain since age 21, education, established risk factors, other neighborhood factors, and clustering by block group.Results: Lower nSES was associated with lower breast cancer risk [quintile 1 vs. 5: HR, 0.79; 95% confidence interval (CI), 0.66-0.95], with a more pronounced association observed in Latinos (quintile 1 vs. 5: HR, 0.60; 95% CI, 0.43-0.85). More urban environments were associated with lower breast cancer risk in Japanese Americans (quintile 5 vs. 1: HR, 0.49; 95% CI, 0.26-0.90), and lower mixed-land development was associated with higher breast cancer risk in Latinos (quintile 1 vs. 5: HR, 1.46; 95% CI, 1.10-1.93).Conclusions: Obesogenic neighborhood environment factors, especially nSES, urbanicity, and mixed-land development, were differentially and independently associated with breast cancer risk in this multiethnic population.Impact: These findings highlight the need for additional studies of the driving contextual aspects of nSES that influence breast cancer risk. Cancer Epidemiol Biomarkers Prev; 26(4); 480-9. ©2017 AACRSee all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population Sciences."

Exploring Differences in the Aspirin-Colorectal Cancer Association by Sex and Race/Ethnicity: The Multiethnic Cohort Study.

BACKGROUND: Evidence has accumulated that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer. We tested whether the inverse associations between NSAIDs and colorectal cancer is similarly observed across sexes and five racial/ethnic groups (Japanese, Latino, African American, Native Hawaiian, and white) in the Multiethnic Cohort (MEC) Study. METHODS: During a mean follow-up of 16.1 years, we identified 4,882 invasive incident colorectal cancer cases among 183,199 eligible participants. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). RESULTS: Use of aspirin and other NSAIDs was associated with a lower incidence of colorectal cancer in men (HR = 0.77; 95% CI, 0.69-0.86 for current vs. never users of aspirin) but not in women (Pinteraction = 0.005). Among male current users, a reduced risk was observed with ≥6 years of aspirin or total NSAID use. The inverse association with current NSAID use in men was observed in all racial/ethnic groups, except for Native Hawaiians, and was stronger in whites. CONCLUSIONS: Our findings suggest that the benefit of NSAIDs for colorectal cancer may be strongest for white men and generalizes to African American, Japanese, and Latino, but not to Native Hawaiian men. The lack of inverse association observed in women and Native Hawaiian men in the MEC should be interpreted with caution. IMPACT: As only very few ethnic/racial groups are likely to be represented in trials of NSAIDs and colorectal cancer, it is important to conduct prospective observational studies in various populations to test the generalizability of their results. Cancer Epidemiol Biomarkers Prev; 26(2); 162-9. ©2016 AACR.

The influence of energy standardisation on the alternate Mediterranean diet score and its association with mortality in the Multiethnic Cohort.

The alternate Mediterranean diet (aMED) score is an adaptation of the original Mediterranean diet score. Raw (aMED) and energy-standardised (aMED-e) versions have been used. How the diet scores and their association with health outcomes differ between the two versions is unclear. We examined differences in participants' total and component scores and compared the association of aMED and aMED-e with all-cause, CVD and cancer mortality. As part of the Multiethnic Cohort, 193 527 men and women aged 45-75 years from Hawaii and Los Angeles completed a baseline FFQ and were followed up for 13-18 years. The association of aMED and aMED-e with mortality was examined using Cox's regression, with adjustment for total energy intake. The correlation between aMED and aMED-e total scores was lower among people with higher BMI. Participants who were older, leaner, more educated and consumed less energy scored higher on aMED-e components compared with aMED, except for the red and processed meat and alcohol components. Men reporting more physical activity scored lower on most aMED-e components compared with aMED, whereas the opposite was observed for the meat component. Higher scores of both aMED and aMED-e were associated with lower risk of all-cause, CVD and cancer mortality. Although individuals may score differently with aMED and aMED-e, both scores show similar reductions in mortality risk for persons scoring high on the index scale. Either version can be used in studies of diet and mortality. Comparisons can be performed across studies using different versions of the score.

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Among 4 Diet Quality Indexes, Only the Alternate Mediterranean Diet Score Is Associated with Better Colorectal Cancer Survival and Only in African American Women in the Multiethnic Cohort.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, with a 5-y survival rate of ∼65%. Therefore, the identification of modifiable health factors to improve CRC survival is crucial. OBJECTIVE: We investigated the association of 4 prediagnostic a priori diet quality indexes with CRC-specific and all-cause mortality in the Multiethnic Cohort (MEC). METHODS: The MEC included >215,000 African-American, Native Hawaiian, Japanese-American, Latino, and white adults living in Hawaii and California who completed a validated quantitative food-frequency questionnaire in 1993-1996. CRC cases and deaths were identified through linkages to cancer registries and to state and national vital registries. Sex-specific HRs and 95% CIs were estimated for the Healthy Eating Index (HEI) 2010, the Alternative HEI (AHEI) 2010, the alternate Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) index with CRC-specific and overall mortality as the primary outcomes. Ethnicity-specific analyses were the secondary outcomes. RESULTS: Among 4204 MEC participants diagnosed with invasive CRC through 2010, 1976 all-cause and 1095 CRC-specific deaths were identified. A higher aMED score was associated with lower CRC-specific mortality in women [HR continuous pattern score divided by its respective SD (HR1SD): 0.86; 95% CI: 0.77, 0.96] but not in men (HR1SD: 1.01; 95% CI: 0.92, 1.11). A higher aMED score was also associated with lower all-cause mortality in women (HR1SD: 0.88; 95% CI: 0.81, 0.96) but not in men (HR1SD: 1.00; 95% CI: 0.93, 1.07). The HEI-2010, AHEI-2010, and DASH index were not significantly associated with CRC-specific or with all-cause mortality. The inverse relation for the aMED score was limited to African Americans and to colon (compared with rectal) cancer. CONCLUSIONS: The aMED score was related to lower mortality only in African-American women (1 of 5 ethnic groups studied). The results should be interpreted with caution due to the small numbers of cases within ethnic groups and the issue of multiple testing.

Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population.

OBJECTIVES: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. MATERIALS AND METHODS: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2. RESULTS AND CONCLUSION: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.