Alcohol intake and endogenous sex hormones in women: Meta-analysis of cohort studies and Mendelian randomization.

BACKGROUND: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. METHODS: Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984). RESULTS: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively). CONCLUSIONS: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.

Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

BACKGROUND: Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. METHODS: Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. RESULTS: Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). CONCLUSIONS: Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.

Plant-based dietary patterns and mortality from all causes, cardiovascular disease, and cancer: The Multiethnic Cohort Study.

BACKGROUND & AIMS: Plant-based dietary patterns have been associated with lower risk of cardiovascular disease (CVD), some cancers, and related mortality in U.S. POPULATIONS: However, the quality of plant foods has rarely been considered in the association between plant-based diets and mortality, especially in a population with various racial and ethnic backgrounds. We investigated whether the adherence to plant-based dietary patterns and the healthiness of plant foods are associated with mortality from all causes, CVD, and cancer and evaluated how the association varies by race and ethnicity. METHODS: A total of 144,729 African American, Japanese American, Latino, Native Hawaiian, and White men and women who participated in the Multiethnic Cohort Study (1993-2019) were included. Cox models were used to estimate HR and 95% CI of mortality from all causes, CVD, and cancer across quintiles of three plant-based diet scores: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). RESULTS: Over an average 21 years of follow-up, we identified 65,087 deaths, including 18,663 from CVD and 16,171 from cancer. Comparing the highest versus lowest quintiles, greater scores of PDI and hPDI were associated with a lower risk of all-cause mortality in both men (HR = 0.85, 95% CI: 0.82-0.89 for PDI; HR = 0.88, 95% CI: 0.85-0.91 for hPDI; both P for trend <0.0001) and women (HR = 0.89, 95% CI: 0.86-0.93 for PDI; HR = 0.86, 95% CI: 0.83-0.89 for hPDI; both P for trend <0.0001). An increased risk of all-cause mortality with uPDI was observed only in women (HR = 1.11, 95% CI: 1.07-1.15, P for trend <0.0001; P for heterogeneity by sex = 0.019). A similar trend was shown for CVD mortality with a significant increase in risk with uPDI for both men and women. PDI was associated with a lower risk of cancer mortality in men (HR = 0.86, 95% CI: 0.80-0.92, P for trend <0.0001), while neither hPDI nor uPDI was associated in either sex. Compared with the other racial and ethnic groups within each sex, the association of uPDI with all-cause mortality was stronger in White men (P for heterogeneity by race and ethnicity = 0.009) and weaker in Latino women (P for heterogeneity = 0.002). CONCLUSION: A healthy plant-based dietary pattern emphasizing the quality of plant foods was associated with a lower risk of all-cause and CVD mortality in both men and women, although the magnitude of the associations varied across racial and ethnic groups.

Effect of Intermittent vs. Continuous Energy Restriction on Visceral Fat: Protocol for The Healthy Diet and Lifestyle Study 2 (HDLS2).

Obesity in the United States and Western countries represents a major health challenge associated with an increased risk of metabolic diseases, including cardiovascular disease, hypertension, diabetes, and certain cancers. Our past work revealed a more pronounced obesity-cancer link in certain ethnic groups, motivating us to develop a tailored dietary intervention called the Healthy Diet and Lifestyle 2 (HDLS2). The study protocol is described herein for this randomized six-month trial examining the effects of intermittent energy restriction (5:2 Diet) plus the Mediterranean dietary pattern (IER + MED) on visceral adipose tissue (VAT), liver fat, and metabolic biomarkers, compared to a standard MED with daily energy restriction (DER + MED), in a diverse participant group. Using MRI and DXA scans for body composition analysis, as well as metabolic profiling, this research aims to contribute to nutritional guidelines and strategies for visceral obesity reduction. The potential benefits of IER + MED, particularly regarding VAT reduction and metabolic health improvement, could be pivotal in mitigating the obesity epidemic and its metabolic sequelae. The ongoing study will provide essential insights into the efficacy of these energy restriction approaches across varied racial/ethnic backgrounds, addressing an urgent need in nutrition and metabolic health research. Registered Trial, National Institutes of Health, ClinicalTrials.gov (NCT05132686).

Intake of sugar and food sources of sugar and colorectal cancer risk in the Multiethnic Cohort Study.

BACKGROUND: The influence of sugar intake on the risk of colorectal cancer (CRC) remains controversial and there is a need to investigate heterogeneity of effects among race and ethnic group. OBJECTIVE: To examine the association of intake of simple sugars and their food sources with CRC risk according to race/ethnicity in a multiethnic cohort study. METHODS: We analyzed data from 192,651 participants who participated in the Multiethnic Cohort Study comprising African American, Japanese American, Latino, Native Hawaiian, and White older adults living in Hawaii and California with an average follow-up of 19 years. Intakes of total and specific types of sugars and sugary foods were estimated from a quantitative food frequency questionnaire completed by the participants in 1993-1996. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk according to quintiles (Q) of sugar and food intakes using Cox models adjusted for potential confounders. RESULTS: As of December 2017, 4,403 incident CRC cases were identified. Among all participants, multivariable-adjusted CRC HRs for Q2, Q3, Q4 and Q5 vs. Q1 for total sugars were 1.03 (95% CI: 0.94, 1.13), 1.05 (0.96, 1.16), 1.12 (1.01, 1.24), and 1.13 (1.01, 1.27), respectively. A similar positive association was observed for total fructose, glucose, fructose, and maltose but not for added sugars and sugary foods. The increased risk appeared to be limited to colon cancer and to be strongest among younger participants (i.e., 45-54 years at baseline); an association with CRC was observed for sugar-sweetened beverages in the latter group. Among race and ethnic groups, increased risk of CRC was most apparent in Latinos. CONCLUSION: In this diverse cohort, intakes of total sugar, total fructose, glucose, fructose, and maltose were associated with an increased risk of CRC and the association was strongest for colon cancer, younger participants, and Latinos.

Arecoline in buccal cells reflects Areca nut dose.

Areca nut (AN) is a carcinogen; its chewing cessation is, therefore, of worldwide interest. However, cessation biomarkers are lacking. We sought to establish arecoline in chewers' buccal cells (BCs) as a biomarker for AN dose. Self-reported AN doses, expressed as the average AN load ("AANL"), the product of AN amount, chewing time, and chewing frequency, were correlated by regression analysis with chewers' BC arecoline, measured by liquid chromatography mass spectrometry. We then determined whether associations differed between Class 1 chewers (who consume AN alone or with slaked lime, leaf, and/or spices) and Class 2 chewers (who consume any combination of the aforementioned ingredients plus tobacco). Among the 103 chewers, 28 Class 1 and 39 Class 2 chewers had detectable arecoline levels, which were used for analyses. A linear regression of cube-root transformed AANL on equally transformed BC arecoline levels provided the best model fit; resulting slopes and corresponding correlation coefficients were 0.86 and 0.40 (p < 0.01) for all; 1.09 and 0.51 (p < 0.01) for Class 1 chewers; 0.35 and 0.17 (p = 0.29) for Class 2 chewers; and 0.94 and 0.45 (p < 0.01), and 0.79 and 0.37 (p = 0.08), respectively, for those who included or excluded lime. Relationships between AANL and BC arecoline levels were similar between chewers who included or excluded lime (p = 0.76), but less between chewing classes (p = 0.14). This provides confidence that BC arecoline can generally act as a reliable biomarker for AN dose, useful for estimating efficacy in AN cessation studies and population-based chewing assessments.

Acculturation and Health Status in the Children's Healthy Living Program in the Pacific Region.

Acculturation/enculturation has been found to impact childhood health and obesity status. The objective of this study is to use cross-sectional data to examine the association between proxies of adult/caregiver acculturation/enculturation and child health status (Body Mass Index [BMI], waist circumference [WC], and acanthosis nigricans [AN]) in the U.S.-Affiliated Pacific Islands (USAPI), Alaska, and Hawai'i. Study participants were from the Children's Healthy Living (CHL) Program, an environmental intervention trial and obesity prevalence survey. Anthropometric data from 2-8 year olds and parent/caregiver questionnaires were used in this analysis. The results of this study (n = 4121) saw that those parents/caregivers who identified as traditional had children who were protected against overweight/obesity (OWOB) status and WC > 75th percentile (compared to the integrated culture identity) when adjusted for significant variables from the descriptive analysis. AN did not have a significant association with cultural classification. Future interventions in the USAPI, Alaska, and Hawai'i may want to focus efforts on parents/caregivers who associated with an integrated cultural group as an opportunity to improve health and reduce child OWOB prevalence.

Thyroid Cancer Survival in the Multiethnic Cohort Study.

OBJECTIVE: The US 5-year survival rate after thyroid cancer (TC) diagnosis is over 95%. Our aim was to investigate survival differences by sex and race and ethnicity in a multiethnic US population. DESIGN: In the Multiethnic Cohort (MEC) study, a total of 605 incident TC cases were identified by linkage to HI and CA statewide cancer registries. Cox models were performed to compare the risk of all-cause mortality among TC cases by sex and race and ethnicity, with adjustment for age, first course of treatment, baseline body mass index, smoking status, alcohol intake, and neighborhood socioeconomic status. Survival among cases was also compared to matched MEC controls with no thyroid cancer. RESULTS: After a mean follow-up of 10.1 years, 250 deaths occurred among TC cases, including 63 deaths attributed to thyroid cancer. The median survival was 14.7 years, and the 5-year age-adjusted overall survival was 84.4% for female cases and 68.7% for male cases (p < 0.0001, HR 2.28 (95% CI: 1.72, 3.01)). Age-adjusted survival was lower among African American, Native Hawaiian, and Filipino cases, compared to Japanese American cases, with Whites and Latinos being intermediate. Men and Filipinos were found to have excess mortality due to thyroid cancer compared to controls (adjusted HR 1.39, 95% CI: 1.11, 1.74; HR 1.62, 95% CI: 1.04, 2.53, respectively). CONCLUSIONS: Sex and racial and ethnic disparities in survival among TC cases were similar to those found in the general population. However, cases with TC had an excess risk of death among males and for Filipinos.

Avocado and Guacamole Consumption and Colorectal Cancer Risk: The Multiethnic Cohort Study.

Dietary fiber and phytonutrients can protect against colorectal cancer, yet their consumption is low in the US. Avocados are a potential source of these beneficial nutrients. Therefore, this study aimed to examine the relationship between avocados/guacamole consumption and colorectal cancer risk in the Multiethnic Cohort Study. We assessed avocados/guacamole consumption by using a food frequency questionnaire. We classified participants into three consumer groups: <1 serving/month, 1-3 servings/month, and ≥1 serving/week with one serving defined as ½ avocado or ½ cup. Colorectal cancer cases were ascertained through the Surveillance, Epidemiology and End Results Program cancer registries. Cox proportional hazards models of colorectal cancer were used to calculate hazard ratios and 95% confidence intervals across avocados/guacamole intake groups in each sex overall and by anatomic subsite (i.e., right colon, left colon, and rectum) and race and ethnicity. Of 192,651 eligible participants, 62.8% reported consuming <1 serving/month avocados/guacamole, 26.7% reported 1-3 servings/month, and 10.5% reported ≥1 serving/week. When adjusted for relevant covariates, there was no significant association with incident colorectal cancer overall, for subsites, or within racial and ethnic subgroups (all p for trend ≥ 0.06). In this large prospective cohort study, we did not find that consumption of avocados/guacamole was associated with colorectal cancer risk.

Time to Diagnosis and Treatment Initiation During the COVID-19 Pandemic Among Rural Patients With Cancer.

Time to diagnosis (TTD) and treatment initiation (TTI) are important measures of access to and quality of cancer care. This study addressed the knowledge gap on the impact of the COVID-19 pandemic on TTD and TTI for rural cancer patients. Sixty-three cancer patients residing in rural areas of the state of Hawaii were surveyed in 2020 to 2021. Overall, 67.5% of participants reported TTD within one month of reporting symptoms to a health care provider. Mean TTI for the overall sample was 55.3 days, and among breast cancer patients, 57.9 days. Compared with pre-pandemic state registry data, mean TTI for the overall sample and breast cancer patients were significantly longer than the state registry null value of 40 days (P = .02 and P =.05, respectively). During the COVID-19 pandemic, cancer patients in rural Hawaii experienced substantial delays in TTI compared with pre-pandemic years.

Proportion and Correlates of Children in the US-Affiliated Pacific Region Meeting Sleep, Screen Time, and Physical Activity Guidelines.

INTRODUCTION: Limited data on 24-hour movement behaviors of children aged 5-8 years exist globally. We describe the prevalence and sociodemographic associations of meeting physical activity (PA), sedentary recreational screen time (ST), and sleep guidelines among children from 11 jurisdictions in the US-Affiliated Pacific region. METHODS: Cross-sectional representative data from 1192 children aged 5-8 years living in the US-Affiliated Pacific region were drawn from the baseline 2012-2014 Children's Healthy Living Program. Sleep and moderate- to vigorous-intensity PA were calculated from accelerometry. ST and sociodemographic data were collected from caregiver surveys. The percentage of children meeting the Asia-Pacific 24-hour movement guidelines for PA (≥60 min/d of moderate- to vigorous-intensity PA), sleep (≥9 and ≤ 11 h/d) and ST (≤2 h/d) were calculated. Generalized linear mixed models were used to examine associations with adiposity and sociodemographic variables. RESULTS: Twenty-seven percent (95% confidence interval, 24.6-30.0) of children met integrated guidelines; 98% (96.2-98.0) met PA, 78% (75.4-80.0) met sleep, and 35% (32.6-38.0) met ST guidelines. Females (adjusted odds ratio = 1.40 [95% confidence interval, 1.03-1.91]) and those living in lower-middle-income jurisdictions (2.29 [1.49-3.54]) were more likely to meet ST guidelines. Overweight children (0.62 [0.40-0.96]), those aged 8 years (0.39 [0.22-0.69]), and children with caregivers of an education level of high school or beyond (0.44 [0.29-0.68]) were less likely to achieve ST guidelines. Children from midrange annual household incomes were less likely to meet combined guidelines (0.60 [0.39-0.92]). CONCLUSIONS: Three-quarters of children are not meeting integrated Asia-Pacific 24-hour movement guidelines. Future strategies for reducing ST and increasing integrated guidelines compliance are needed.

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. METHODS: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

The DIRAC framework: Geometric structure underlies roles of diversity and accuracy in combining classifiers.

Combining classification systems potentially improves predictive accuracy, but outcomes have proven impossible to predict. Similar to improving binary classification with fusion, fusing ranking systems most commonly increases Pearson or Spearman correlations with a target when the input classifiers are "sufficiently good" (generalized as "accuracy") and "sufficiently different" (generalized as "diversity"), but the individual and joint quantitative influence of these factors on the final outcome remains unknown. We resolve these issues. Building on our previous empirical work establishing the DIRAC (DIversity of Ranks and ACcuracy) framework, which accurately predicts the outcome of fusing binary classifiers, we demonstrate that the DIRAC framework similarly explains the outcome of fusing ranking systems. Specifically, precise geometric representation of diversity and accuracy as angle-based distances within rank-based combinatorial structures (permutahedra) fully captures their synergistic roles in rank approximation, uncouples them from the specific metrics of a given problem, and represents them as generally as possible.

Epigenome-wide association study of total nicotine equivalents in multiethnic current smokers from three prospective cohorts.

The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies. In the Multiethnic Cohort Study (discovery, n = 1994), TNEs were associated with differential methylation at 408 CpG sites across >250 genomic regions (p < 9 × 10-8). The top significant sites were annotated to AHRR, F2RL3, RARA, GPR15, PRSS23, and 2q37.1, all of which had decreasing methylation with increasing TNEs. We identified 45 novel CpG sites, of which 42 were unique to the EPIC array and eight annotated to genes not previously linked with smoking-related DNA methylation. The most significant signal in a novel gene was cg03748458 in MIR383;SGCZ. Fifty-one of the 408 discovery sites were validated in the Singapore Chinese Health Study (n = 340) and the Southern Community Cohort Study (n = 394) (Bonferroni corrected p < 1.23 × 10-4). Significant heterogeneity by race and ethnicity was detected for CpG sites in MYO1G and CYTH1. Furthermore, TNEs significantly mediated the association between cigarettes per day and DNA methylation at 15 sites (average 22.5%-44.3% proportion mediated). Our multiethnic study highlights the transethnic and ethnic-specific methylation associations with internal nicotine dose, a strong predictor of smoking-related morbidities.

The Association of Alcohol Outlet Density with Alcohol Intake: The Multiethnic Cohort.

OBJECTIVE: Neighborhood characteristics have been shown to influence lifestyle behaviors. Here we characterized alcohol outlet density in Los Angeles County, California, and Hawaii and assessed the association of alcohol outlet density with self-reported alcohol intake in the Multiethnic Cohort. METHOD: Participants (n=178,977) had their addresses geocoded, at cohort entry (1993-1996), and appended to block group-level alcohol outlet densities (on- and off-premises). Multinomial logistic regression was performed to assess the association between self-reported alcohol intake and on- and off-premise alcohol outlet densities by each state. Stratified analysis was conducted by sex, race, and ethnicity. RESULTS: Overall, we did not find associations between alcohol outlet density and self-reported alcohol intake in Los Angeles County, but we found that on-premise alcohol outlets were associated with 59% (OR=1.59, 95% CI:1.29,1.96) increased odds of consuming >2 drinks per day in Hawaii. Women living in neighborhoods with high density of on-premise alcohol outlets (Los Angeles County OR=1.15, 95% CI: 0.95,1.40) and (Hawaii OR=2.07, 95% CI: 1.43,3.01) had an increased odds of >2 drinks per day. CONCLUSION: This study suggests that neighborhood factors are associated with individual level behaviors and that there may be a need for multilevel interventions.

Variation in patterns of second primary malignancies across U.S. race and ethnicity groups: a Surveillance, Epidemiology, and End Results (SEER) analysis.

PURPOSE: One in six incident cancers in the U.S. is a second primary cancer (SPC). Although primary cancers vary considerably by race and ethnicity, little is known about the population-based occurrence of SPC across these groups. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) 12 data and relative to the general population, we calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPC among 2,457,756 Hispanics, non-Hispanic Asian American/Pacific Islanders (NHAAPI), non-Hispanic black (NHB), and non-Hispanic whites (NHW) cancer survivors aged 45 years or older when diagnosed with a first primary cancer (FPC) from 1992 to 2015. RESULTS: The risk of second primary bladder cancer after first primary prostate cancer was higher than expected in Hispanic (SIR = 1.18, 95% CI: 1.01-1.38) and NHAAPI (SIR = 1.41, 95% CI: 1.20-1.65) men than NHB and NHW men. Among women with a primary breast cancer, Hispanic, NHAAPI, and NHB women had a nearly 1.5-fold higher risk of a second primary breast cancer, while NHW women had a 6% lower risk. Among men with prostate cancer whose SPC was diagnosed 2 to <12 months, NHB men were at higher risk for colorectal cancer and Hispanic and NHW men for non-Hodgkin's lymphoma. In the same time frame for breast cancer survivors, Hispanic and NHAAPI women were significantly more likely than NHB and NHW women to be diagnosed with a second primary lung cancer. CONCLUSION: Future studies of SPC should investigate the role of shared etiologies, stage of diagnosis, treatment, and lifestyle factors after cancer survival across different racial and ethnic populations.

Racial and Ethnic Differences in the Population-Attributable Fractions of Alzheimer Disease and Related Dementias.

BACKGROUND AND OBJECTIVES: Previous studies estimated that modifiable risk factors explain up to 40% of the dementia cases in the United States and that this population-attributable fraction (PAF) differs by race and ethnicity-estimates of future impact based on the risk factor prevalence in contemporary surveys. The aim of this study was to determine the race-specific and ethnicity-specific PAF of late-onset Alzheimer disease and related dementias (ADRDs) based on the risk factor prevalence and associations observed on the same individuals within a prospective cohort. METHODS: Data were from Multiethnic Cohort Study participants (African American, Japanese American, Latino, Native Hawaiian, and White) enrolled in Medicare Fee-for-Service. We estimated the PAF based on the prevalence of risk factors at cohort baseline and their mutually adjusted association with subsequent ADRD incidence. Risk factors included low educational attainment and midlife exposures to low neighborhood socioeconomic status, unmarried status, history of hypertension, stroke, diabetes or heart disease, smoking, physical inactivity, short or long sleep duration, obesity, and low-quality diet, as well as APOE ε4 for a subset. RESULTS: Among 91,881 participants (mean age 59.3 at baseline, 55.0% female participants), 16,507 incident ADRD cases were identified from Medicare claims (1999-2016, mean follow-up 9.3 years). The PAF for nongenetic factors combined was similar in men (24.0% [95% CI 21.3-26.6]) and women (22.8% [20.3-25.2]) but varied across Japanese American (14.2% [11.1-17.2]), White (21.9% [19.0-24.7]), African American (27.8% [22.3-33.0]), Native Hawaiian (29.3% [21.0-36.7]), and Latino (33.3% [27.5-38.5]) groups. The combined PAF was attenuated when accounting for competing risk of death, in both men (10.4%) and women (13.9%) and across racial and ethnic groups (4.7%-25.5%). The combined PAF was also different by age at diagnosis and ADRD subtypes, higher for younger (65-74 years: 43.2%) than older (75-84 years: 32.4%; ≥85 years: 11.3%) diagnoses and higher for vascular or unspecified ADRD than for AD or Lewy body dementia. An additional PAF of 11.8% (9.9-13.6) was associated with APOE ε4, which together with nongenetic risk factors accounted for 30.6% (25.8-35.1) of ADRD. DISCUSSION: Known risk factors explained about a third of the ADRD cases but with unequal distributions across racial and ethnic groups.

Dietary intake and visceral adiposity in older adults: The Multiethnic Cohort Adiposity Phenotype study.

Background: There are established links between the accumulation of body fat as visceral adipose tissue (VAT) and the risk of developing obesity-associated metabolic disease. Previous studies have suggested that levels of intake of specific foods and nutrients are associated with VAT accumulation after accounting for total energy intake. Objective: This study assessed associations between a priori selected dietary factors on VAT quantified using abdominal magnetic resonance imaging. Methods: The cross-sectional Multiethnic Cohort Adiposity Phenotype Study included n = 395 White, n = 274 Black, n = 269 Native Hawaiian, n = 425 Japanese American and n = 358 Latino participants (mean age = 69 years ± 3 SD). Participants were enrolled stratified on sex, race, ethnicity and body mass index. General linear models were used to estimate the mean VAT area (cm2) for participants categorized into quartiles based on their dietary intake of selected foods/nutrients adjusting for age, sex, racial and ethnic groups, the total percentage fat from whole-body dual energy X-ray absorptiometry and total energy. Results: There were significant inverse associations with VAT for dietary intake of total vegetables, total fruits (including juice), cereals, whole grains, calcium, copper and dietary fiber (p-trend ≤0.04). Positive trends were observed for VAT for participants who reported higher intake of potatoes, total fat and saturated fatty acids (SFA) (p-trend ≤0.02). Foods/nutrients that met the multiple testing significance threshold were total fruits, whole grains, copper, dietary fiber and SFA intake. Conclusions: These results highlight foods and nutrients including SFA, total fruit, whole grains, fiber and copper as potential candidates for future research to inform dietary guidelines for the prevention of chronic disease among older adults.

Patient reports of cancer care coordination in rural Hawaii.

PURPOSE: Rural residents experience disproportionate burdens of cancer, and poorer cancer health outcomes in rural populations are partly attributed to care delivery challenges. Cancer patients in rural areas often experience unique challenges with care coordination. In this study, we explored patient reports of care coordination among rural Hawaii patients with cancer and compared rural and urban patients' perceptions of cancer care coordination. METHODS: 80 patients receiving active treatment for cancer from rural Hawaii participated in a care coordination study in 2020-2021. Participants completed the Care Coordination Instrument, a validated oncology patient questionnaire. FINDINGS: Mean age of rural cancer patients was 63.0 (SD = 12.1), and 57.7% were female. The most common cancer types were breast and GI. Overall, rural and urban patients' perceptions of care coordination were comparable (p > 0.05). There were statistically significant differences between rural and urban patients' perceptions in communication and navigation aspects of care coordination (p = 0.02 and 0.04, respectively). Specific differences included a second opinion consultation, clinical trial considerations, and after-hours care. 43% of rural patients reported traveling by air for part or all of their cancer treatment. CONCLUSIONS: Findings suggest that while overall perceptions of care coordination were similar between rural and urban patients, differential perceptions of specific care coordination areas between rural and urban patients may reflect limited access to care for rural patients. Improving access to cancer care may be a potential strategy to enhance care coordination for rural patients and ultimately address rural-urban cancer health disparities.