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Summary: The immature brain is highly susceptible to the consequences of very preterm birth with a high rate of long-term neurodisabilities in survivors and high use of specific outpatient services to limit the functional effects of the disabilities. To assess the economic burden for the social and health care system, it is necessary to inventory the community supports and need for special education or rehabilitation used by preterm children. Such studies are few and were done only in extremely low-birthweight or extremely preterm newborns in the United States. Objective: To study the rates of specific outpatient services and special education at 5 years of age and between 5 and 8 years of age in a geographically-defined population of children born very preterm. Design, Setting and Patients: 2901 liveborn children before 33 weeks’gestation (WG) and one control group of 666 liveborn children at 39-40WG were included in nine regions of France in 1997 corresponding to more than one third of all births. At five years, these children had a medical examination and were evaluated by a psychologist at local centres organised for the study in every region. Cognitive function was assessed by the mental processing composite scale (PMC) of the Kauffmann Assessement Battery for Children test, which is considered to be equivalent to intelligence quotient and behavioral difficulties using the Strength and Difficulties questionnaire completed by the parents. Data for dependence or compensatory aids, i.e. occupational therapy or physical therapy, speech therapy, psychologist or psychiatrist visits, orthoptic therapy, wearing glasses, wearing hearing aid, specific equipment to walk (walker, wheelchair…), orthopaedic treatment or anti-epileptic treatment were collected from parents. At eight years, a postal questionnaire was sent to the parents to collect data on specific outpatient services and special treatments at home and school. Stata software was used (version 9.0). Main outcome measures. Parent Questionnaire for identifying children with chronic conditions and specific health care needs at 5 and 8 years and categorization of developmental neurodisabilities based on examination of children and psychometric evaluation at 5 years. Results: At 5 years data were obtained for respectively 1817 and 396 children born before 33WG or at 39-40WG, which represent 80% of the very preterm children and 71% of the at term children. At 8 years we obtained data for 63% of the very preterm children and 59% of the at term children. At 5 years, care in a rehabilitation center and/or specific outpatient services were required for 41% of children born between 24 and 28WG, 32% of children born between 24 and 32WG and 15% of those born at 39-40WG. Between 5 and 8 years, these figures were respectively 61%, 50% and 36%. In the very preterm group, rates of specific outpatient services were higher than 80% if the child had a motor and/or a neurosensory deficit. In case of cognitive deficiencies (PMC < 85), rates of specific outpatient services were low at 37% at 5 years and increases at 63% between 5 and 8 years. Conclusion: Compared to the children born at term, the very preterm children have considerable educational needs, which are inversely related to gestational age at birth and to age of the children at the time of reporting. Despite economic burden, efforts to improve access to services are necessary, in particular in case of cognitive impairment. [Copyright &y& Elsevier]

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .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 Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

This study analyzed the overall quality of the diet using predefined indices, including the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED) score, the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII ® ), to explore their association with the risk of bladder cancer in the Multiethnic Cohort Study. Data were taken from 186,979 African American, Japanese American, Latino, Native Hawaiian, and non-Hispanic White participants aged 45-75 years, with 1152 incident cases of invasive bladder cancer during a mean follow-up period of 19.2 ± 6.6 years. Cox models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with comprehensive adjustment for smoking. Comparing the highest vs. lowest diet quality score quintile, HRs (95% CIs) in men was 1.08 (0.86-1.36) for HEI-2015, 1.05 (0.84-1.30) for AHEI-2010, 1.01 (0.80-1.27) for aMED, 1.13 (0.90-1.41) for DASH, and 0.96 (0.76-1.21) for DII ® , whereas the corresponding HRs for women were 0.75 (0.53-1.07), 0.64 (0.45-0.92), 0.60 (0.40-0.88), 0.66 (0.46-0.95), and 0.63 (0.43-0.90) with all p values for trend <0.05. The inverse association found in women did not vary by smoking status or race and ethnicity. Our findings suggest that adopting high-quality diets may reduce the risk of invasive bladder cancer among women in a multiethnic population.

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., Competing Interests: Conflict of interest All authors declare no conflict of interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke., Methods: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes., Results: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = -2.2 (95% confidence interval (CI):-2.5, -1.9), in Shanghai (n = 1049) (Δ years = -1.6 (95% CI:-2.9, -0.3), and in Sutter Health and Kaiser Permanente Hawai'i in the US (n = 82) (Δ years = -11.3 (95% CI: -17.7, -4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant., Conclusions: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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.

Background: US-born Latinos have a higher incidence of hepatocellular carcinoma (HCC) than foreign-born Latinos. Acculturation to unhealthy lifestyle behaviors and an immigrant self-selection effect may play a role. In this study, the authors examined the influence of generational status on HCC risk among Mexican American adults., Methods: The analytic cohort included 31,377 self-reported Mexican Americans from the Multiethnic Cohort Study (MEC). Generational status was categorized as: first-generation (Mexico-born; n = 13,382), second-generation (US-born with one or two parents born in Mexico; n = 13,081), or third-generation (US-born with both parents born in the United States; n = 4914). Multivariable Cox proportional hazards regression was performed to examine the association between generational status and HCC incidence., Results: In total, 213 incident HCC cases were identified during an average follow-up of 19.5 years. After adjusting for lifestyle and neighborhood-level risk factors, second-generation and third-generation Mexican Americans had a 37% (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.98-1.92) and 66% (HR, 1.66; 95% CI, 1.11-2.49) increased risk of HCC, respectively, compared with first-generation Mexican Americans (p for trend = 0.012). The increased risk associated with generational status was mainly observed in males (second-generation vs. first-generation: HR, 1.60 [95% CI, 1.05-2.44]; third-generation vs. first-generation: HR, 2.08 [95% CI, 1.29-3.37])., Conclusions: Increasing generational status of Mexican Americans is associated with a higher risk of HCC. Further studies are needed to identify factors that contribute to this increased risk., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objectives: In this report, we investigated the association between established risk factors and type 2 diabetes (T2D) across 5 distinct ethnic groups and explored differences according to T2D definition within the Multiethnic Cohort (MEC) Study., Methods: Using the full MEC, with participants in Hawaii and Los Angeles (N=172,230), we applied Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All participants completed questionnaires asking about demographics, anthropometrics, lifestyle factors, and regular diet. T2D status was determined from self-reported diagnosis/medication and Medicare claims. We assessed the associations between well-established risk factors and T2D in the full cohort, after stratification by ethnic group, according to the T2D definition, and in a biorepository subset. Effect modification by ethnicity was evaluated using Wald's tests., Results: Overall, 46,500 (27%) participants had an incident T2D diagnosis after a mean follow-up of 17.1±6.9 years. All predictors were significantly associated with T2D: overweight (HR=1.74), obesity (HR=2.90), red meat intake (HR=1.15), short (HR=1.04) and long (HR=1.08) sleep duration, and smoking (HR=1.26) predicted a significantly higher T2D incidence, whereas coffee (HR=0.90) and alcohol (HR=0.78) consumption, physical activity (HR=0.89), and diet quality (HR=0.96) were associated with lower T2D incidence. The strength of these associations was similar across ethnic groups with noteworthy disparities for overweight/obesity, physical activity, alcohol intake, coffee consumption, and diet quality., Conclusions: These findings confirm the importance of known risk factors for T2D across ethnic groups, but small differences were detected that may contribute to disparate incidence rates in some ethnic groups, especially for obesity and physical activity., (Copyright © 2023 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Given the role of the immune system in non-Hodgkin lymphoma (NHL) etiology, obesity and type 2 diabetes (T2D) may impact NHL development. We examined the association of body mass index (BMI) and T2D with NHL in the multiethnic cohort (MEC)., Methods: The MEC recruited >215,000 participants in Hawaii and Los Angeles from five racial/ethnic groups; NHL cases were identified through cancer registry linkages. T2D status, and BMI at age 21 and cohort entry were derived from repeated self-reports; for T2D, Medicare claims were also applied. HRs and 95% confidence intervals (CI) for BMI and T2D as predictors of NHL were determined using Cox regression adjusted for relevant covariates., Results: Among 192,424 participants, 3,472 (1.8%) with NHL and 68,850 (36%) with T2D after 19.2 ± 6.6 years follow-up, no significant association between T2D and NHL (HR, 1.04; 95% CI, 0.96-1.13) was observed. Stratification by BMI at cohort entry showed a significant association of T2D with NHL among individuals with normal weight only (HR, 1.18; 95% CI, 1.03-1.37). In a model with both BMI values plus T2D, only overweight (HR, 1.13; 95% CI, 1.01-1.26) and obesity (HR, 1.25; 95% CI, 0.99-1.59) at age 21 were associated with NHL incidence. Stratification by sex, race/ethnicity, and NHL subtype indicated no differences., Conclusions: Our findings suggest an association between T2D and NHL incidence in several subgroups but not in the total population and an elevated risk related to early-life BMI., Impact: Excess body weight in early life, rather than T2D, may be a predictor of NHL incidence., (©2023 American Association for Cancer Research.)

Background: Research on the association between type 2 diabetes (T2D) and bladder cancer (BCA) risk among non-European ancestry populations is sparse to nonexistent, and most prior studies rely on a single baseline assessment of T2D status., Methods: We estimated the T2D-BCA association using the Multiethnic Cohort Study of 185,059 men and women in California and Hawaii. Participants were African American, European American, Japanese American, Latin American, and Native Hawaiian, ages 45-75 years at enrollment (1993-1996). T2D was assessed by self-report at baseline, follow-up surveys, and Medicare claims. Cases were identified using Surveillance, Epidemiology and End Results Program cancer registries through 2016. Associations were estimated by race/ethnicity using Cox proportional hazards regression. Adjusted attributable fractions (AAF) and cumulative absolute risk of bladder cancer were estimated across groups., Results: Over an average 19.7 years of follow-up 1,890 incident bladder cancer cases were diagnosed. Time-varying T2D was associated with bladder cancer in the multiethnic sample (HR = 1.17; 95% confidence interval, 1.05-1.30); however, the HR did not differ by race/ethnicity ( P = 0.85). The AAF was 4.2% in the multiethnic sample and largest among Native Hawaiians (9.8%). Absolute risk of bladder cancer among European Americans without T2D was higher than all other groups with T2D., Conclusion: T2D is significantly associated with bladder cancer risk in a multiethnic sample., Significance: Those with T2D have higher incidence of bladder cancer, regardless of racial/ethnic group. Reducing T2D prevalence could substantially lower bladder cancer incidence among Native Hawaiians due to T2D being more common in this group. High absolute risk of bladder cancer among European Americans, regardless of T2D status, indicates that elevated bladder cancer risk in this group may be due to factors other than T2D. Future studies must explore reasons for this difference in incidence., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: White rice is a staple food for Japanese, a population at high risk for colorectal cancer (CRC). We investigated the association between white rice intake and CRC among Japanese Americans in the Multiethnic Cohort (MEC) study., Methods: The MEC study is a prospective study established in Hawaii and California in 1993-1996. Usual dietary intake was assessed using a validated quantitative food frequency questionnaire at baseline. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of intake and to perform trend tests across sex-specific quartiles with adjustment for relevant confounders., Results: We identified 1,553 invasive CRC cases among 49,136 Japanese Americans (23,595 men and 25,541 women) during a mean follow-up of 19 years. White rice consumption was not associated with overall CRC incidence in men (P trend = 0.11) or women (P trend = 0.56). After excluding participants with a history of diabetes, the inverse associations were significant for CRC (P trend = 0.03, HR for quartile 4 [Q4] vs quartile 1 [Q1], 0.81; 95% CI, 0.64-1.03) and tumors of the distal colon (P trend = 0.006, HR for Q4 vs Q1, 0.66; 95% CI, 0.44-0.99) among men but not women., Conclusion: White rice consumption was not associated with an increased risk of overall CRC among Japanese Americans. An inverse association was observed with risk of CRC and distal colon cancer in men without a history of diabetes.

Introduction: We investigated whether the protective association of physical activity with risk of Alzheimer's disease and related dementias (ADRD) has genetic or behavioral variations., Methods: In the Multiethnic Cohort, we analyzed moderate or vigorous physical activity (MVPA) reported at ages 45 to 75 among 88,047 participants in relation to 13,039 incident diagnoses of late-onset ADRD identified in Medicare claims (1999 to 2014), by five racial and ethnic groups, hours sitting, and in a subset (16%), apolipoprotein E (APOE) genotype., Results: MVPA was inversely associated with ADRD (hazard ratio for ≥14 vs <2.5 hours/week: 0.83, 95% confidence interval [CI]: 0.76 to 0.90 in men; 0.88, 5% CI: 0.81 to 0.95 in women). The association was inverse in all racial and ethnic groups except Black participants (P-heterogeneity = 0.52), but stronger in individuals with lower levels of sitting duration or those who do not carry the APOE e4 risk allele., Discussion: The different effects of physical activity by sitting duration and APOE genotype warrant further research., (© 2022 the Alzheimer's Association.)

Introduction: Data are limited for comparison of sex- and race/ethnicity-specific risks of Alzheimer's disease and related dementia (ADRD)., Methods: In the population-based Multiethnic Cohort, we estimated the age-standardized diagnostic incidence rate (ASDIR) and relative risk of late-onset ADRD (n = 16,410) among 105,796 participants based on Medicare claims (1999-2014) by sex and race/ethnicity., Results: The ASDIR for ADRD was higher for women (17.0 per 1000 person-years) than for men (15.3) and varied across African Americans (22.9 in women, 21.5 in men), Native Hawaiians (19.3, 19.4), Latinos (16.8, 14.7), Whites (16.4, 15.5), Japanese Americans (14.8, 13.8), and Filipinos (12.5, 9.7). Similar risk patterns were observed for AD. Adjustment for education and cardiometabolic diseases attenuated the differences. Accounting for deaths from competing causes increased the sex difference, while reducing the racial/ethnic differences. Less racial/ethnic disparity was detected among apolipoprotein E (APOE) e4 carriers., Discussion: More research is needed to understand the sex and racial/ethnic differences in ADRD., (© 2021 the Alzheimer's Association.)

Background: Latinos are the largest minority group in the United States. We assessed cancer mortality by birthplace and generation status of Mexican Latinos in the Multiethnic Cohort., Methods: We included 26 751 Latinos of Mexican origin and 6093 non-Latino Whites aged 45-74 years at cohort entry (1993-1996) from the California Multiethnic Cohort component. The Mexican Latinos comprised 42% first-generation Mexico-born immigrants, 42% second-generation (28% US-born with both parents Mexico-born and 14% US-born with 1 parent US-born and 1 parent Mexico-born), and 16% third-generation or more who were US-born with both parents US-born. Multivariable Cox models were used to calculate covariate adjusted hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality by birthplace and generation status. All statistical tests were 2-sided., Results: Cancer death rate was highest among the US-born with 1 parent US-born and 1 parent Mexico-born (age-adjusted rate = 471.0 per 100 000 person-years) and US-born with both parents US-born (age-adjusted rate = 469.0 per 100 000 person-years) groups. The US-born with both parents Mexico-born group had a 30% (hazard ratio = 1.30, 95% confidence interval = 1.18 to 1.44) higher risk of cancer death than the first-generation Mexico-born immigrants group, showing US birthplace was associated with an elevated cancer mortality. For cancer-specific mortality, US birthplace was positively associated with colorectal, liver and lung, and ovarian cancer (P values ranged from .04 to .005). Among US-born Mexican Latinos, generation status was not statistically significantly associated with overall cancer or site-specific cancer mortality., Conclusions: Our findings suggest that US birthplace is a risk factor for cancer death in Mexican Americans. Identification of the contributing factors is important to curtail patterns of increasing cancer mortality in US-born Mexican Latinos., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

High-quality diets have been found to be beneficial in preventing long-term weight gain. However, concurrent changes in diet quality and body weight over time have rarely been reported. We examined the association between 10-year changes in diet quality and body weight in the Multiethnic Cohort Study. Analyses included 53 977 African Americans, Native Hawaiians, Japanese Americans, Latinos and Whites, who completed both baseline (1993-1996, 45-69 years) and 10-year follow-up (2003-2008) surveys including a FFQ and had no history of heart disease or cancer. Using multivariable regression, weight changes were regressed on changes in four diet quality indexes, Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet and Dietary Approaches to Stop Hypertension scores. Mean weight change over 10 years was 1·2 (sd 6·8) kg in men and 1·5 (sd 7·2) kg in women. Compared with stable diet quality (< 0·5 sd change), the greatest increase (≥ 1 sd increase) in the diet scores was associated with less weight gain (by 0·55-1·17 kg in men and 0·62-1·31 kg in women). Smaller weight gain with improvement in diet quality was found in most subgroups by race/ethnicity, baseline age and baseline BMI. The inverse association was stronger in younger age and higher BMI groups. Ten-year improvement in diet quality was associated with a smaller weight gain, which varied by race/ethnicity and baseline age and BMI. Our findings suggest that maintaining a high-quality diet and improving diet quality over time may prevent excessive weight gain.

Purpose: Visceral adipose tissue (VAT) may be more important than subcutaneous fat in type 2 diabetes (T2D) etiology. We examined a VAT score developed in reference to MRI measurement of VAT in the Multiethnic Cohort (MEC) as a risk factor for incident T2D., Methods: Two nested case-control studies of cancer allowed calculation of the VAT score based on anthropometric measures and 8 biomarkers among 2,556 participants without T2D. Incident cases were identified from Medicare linkages and self-reports after blood draws in 2001-2006. Cox regression with age as time metric was applied to estimate the association of the VAT score with T2D., Results: During 10.1 ± 2.4 years, 355 incident T2D cases were identified. VAT scores were higher in T2D cases than among those without disease (5.06±0.43 vs. 4.95±0.41; P<0.0001) and significantly associated with T2D (HR = 2.70; 95%CI 1.60, 4.58 per unit) with similar values in men (HR = 2.99; 95%CI 1.03, 8.73) and women (HR = 2.61; 95%CI 1.39, 4.91). A significant association was observed in all five ethnic groups but only statistically significant among Japanese Americans (HR = 6.24; 95%CI 2.34, 16.68)., Conclusion: These findings support that VAT as estimated by a biomarker-based score predicts T2D incidence beyond BMI in particular among older adults of Japanese ancestry., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA)., Methods: Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60-65. Differentially methylated CpGs by race/ethnicity (DM-CpGs) were identified by linear regression (Bonferroni-corrected P < 0.1) and analyzed in relation to corresponding gene expression, a priori selected single nucleotide polymorphisms (SNPs), and blood biomarkers of inflammation and metabolism using Pearson or Spearman correlations (FDR < 0.1)., Results: We identified 174 DM-CpGs with the majority of hypermethylated in JPA compared to EUA (n = 133), often in promoter regions (n = 48). Half (51%) of the genes corresponding to the DM-CpGs were involved in liver function and liver disease, and the methylation in nine genes was significantly correlated with gene expression for DM-CpGs. A total of 156 DM-CpGs were associated with rs7489665 (SH2B1). Methylation of DM-CpGs was correlated with blood levels of the cytokine MIP1B (n = 146). We confirmed some of the DM-CpGs in the TCGA adjacent non-tumor liver tissue of Asians versus EUA., Conclusion: We found a number of differentially methylated CpGs in blood DNA between JPA and EUA women with a potential link to liver disease, specific SNPs, and systemic inflammation. These findings may support further research on the role of DNA methylation in mediating some of the higher risk of liver disease among JPA., (© 2021. The Author(s).)

Ultrafine particles (UFP; diameter less than or equal to 100 nm) may reach the brain via systemic circulation or the olfactory tract and have been implicated in the risk of brain tumors. The effects of airport-related UFP on the risk of brain tumors are not known. Here we determined the association between airport-related UFP and risk of incident malignant brain cancer ( n = 155) and meningioma ( n = 420) diagnosed during 16.4 years of follow-up among 75,936 men and women residing in Los Angeles County from the Multiethnic Cohort study. UFP exposure from aircrafts was estimated for participants who lived within a 53 km × 43 km grid area around the Los Angeles International Airport (LAX) from date of cohort entry (1993-1996) through December 31, 2013. Cox proportional hazards models were used to estimate the effects of time-varying, airport-related UFP exposure on risk of malignant brain cancer and meningioma, adjusting for sex, race/ethnicity, education, and neighborhood socioeconomic status. Malignant brain cancer risk in all subjects combined increased 12% [95% confidence interval (CI), 0.98-1.27] per interquartile range (IQR) of airport-related UFP exposure (∼6,700 particles/cm 3 ) for subjects with any address in the grid area surrounding the LAX airport. In race/ethnicity-stratified analyses, African Americans, the subgroup who had the highest exposure, showed a HR of 1.32 (95% CI, 1.07-1.64) for malignant brain cancer per IQR in UFP exposure. UFP exposure was not related to risk of meningioma overall or by race/ethnicity. These results support the hypothesis that airport-related UFP exposure may be a risk factor for malignant brain cancers. SIGNIFICANCE: Malignant brain cancer risk increases with airport-related UFP exposure, particularly among African Americans, suggesting UFP exposure may be a modifiable risk factor for malignant brain cancer., (©2021 American Association for Cancer Research.)

Introduction: Compared to non-Hispanic Whites, Japanese Americans, Native Hawaiians, and African Americans have higher incidences of pancreatic cancer (PCa) that are not entirely explained by rates of obesity but may be explained by weight changes throughout adulthood., Methods: The multiethnic cohort is a population-based prospective cohort study that has followed 155,308 participants since its establishment between 1993 and 1996. A total of 1,328 incident cases with invasive PCa were identified through 2015. We conducted separate multivariable Cox proportional hazards models for self-reported weight-change and BMI-change (age 21 to cohort entry) to determine the association with PCa risk, adjusting for potential confounders including weight or BMI at age 21., Results: The mean age at cohort entry was 59.3 years (SD 8.9). An increased risk of PCa was associated with: 1) weight (HR per10 lbs = 1.06; 95% CI = 1.03-1.09) or BMI (HR per kg/m 2  = 1.04; 95% CI = 1.02-1.05) at age 21; and 2) weight (HR per 10 lbs = 1.03; 95% CI = 1.01-1.05) or BMI (HR = 1.02; 95% CI = 1.00-1.03) at cohort entry. We found increased risk of PCa between weight (HR per 10 lbs = 1.03; 95% CI = 1.01-1.05) and BMI (HR per 5 kg/m 2  = 1.08; 95% CI = 1.01-1.15) change from age 21 to baseline. There were significant interactions between race/ethnicity and weight (p = 0.008) or BMI (p = 0.03) at baseline, and weight (p = 0.02) or BMI (p = 0.02) change. Weight and BMI change through adulthood significantly increased the risk of PCa for Japanese Americans and Latinos, but not for African American, White, or Hawaiian participants., Conclusion: Our findings indicate that weight or BMI gain has a significant and independent impact on PCa risk, specifically among Latinos and Japanese Americans., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The association between prediagnostic antibody responses to Fusobacterium nucleatum ( F. nucleatum ) and subsequent risk of colorectal cancer is not established., Methods: We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States., Results: Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and colorectal cancer risk., Conclusions: Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of colorectal cancer., Impact: Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue samples., (©2021 American Association for Cancer Research.)

Background: Anthropometric and hormone-related factors are established endometrial cancer risk factors; however, little is known about the impact of these factors on endometrial cancer risk in non-White women., Methods: Among 110,712 women participating in the Multiethnic Cohort (MEC) Study, 1150 incident invasive endometrial cancers were diagnosed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with endometrial cancer risk for race/ethnicity and for risk factors across racial/ethnic groups were calculated., Results: Having a higher body mass index (BMI) at baseline or age 21 years was strongly associated with increased risk (p int race/ethnicity ≥ 0.36). Parity (vs nulliparity) was inversely associated with risk in all the groups except African Americans (p int 0.006). Current use of postmenopausal hormones at baseline (PMH-E; vs never use) was associated with increased risk in Whites and Japanese Americans (p int 0.002). Relative to Whites, endometrial cancer risk was lower in Japanese Americans and Latinas and non-significantly higher in Native Hawaiians. Risk in African Americans did not differ from that in Whites., Conclusions: Racial/ethnic differences in endometrial cancer risk were not fully explained by anthropometric or hormone-related risk factors. Further studies are needed to identify reasons for the observed racial/ethnic differences in endometrial cancer risk.

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 (∑LMHM molar ) 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) (P trend  = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA OR T3 vs T1  = 2.66, 95% CI 1.39-5.12, P trend  = 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 (OR above 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.

Background: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer., Methods: Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression., Results: Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09-1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62-3.19), but not thereafter (OR, 0.97; 95% CI, 0.76-1.24)., Conclusions: In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw., Impact: Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer., (©2020 American Association for Cancer Research.)

Introduction: Cyanoethyl mercapturic acid (CEMA) is a urinary metabolite of acrylonitrile, a toxicant found in substantial quantities in cigarette smoke, but not in non-combusted products such as e-cigarettes or smokeless tobacco and rarely in the diet or in the general human environment. Thus, we hypothesized that CEMA is an excellent biomarker of combusted tobacco product use., Aims and Methods: We tested this hypothesis by analyzing CEMA in the urine of 1259 cigarette smokers (urinary cotinine ≥25 ng/mL) and 1191 nonsmokers. The analyses of CEMA and cotinine were performed by validated liquid chromatography-tandem mass spectrometry methods. Logistic regression was fit for log-transformed CEMA to construct the receiver operating characteristic curve., Results: We found that a CEMA cutpoint of 27 pmol/mL urine differentiated cigarette smokers from nonsmokers with sensitivity and specificity greater than 99%. The use of different cotinine cutpoints to define smokers (10-30 ng/mL) had little effect on the results., Conclusions: CEMA is a highly reliable urinary biomarker to identify users of combusted tobacco products such as cigarettes as opposed to users of non-combusted products, medicinal nicotine, or nonusers of tobacco products., Implications: CEMA can be used to distinguish users of combusted tobacco products from non-combusted products such as e-cigarettes, smokeless tobacco, and medicinal nicotine. Levels of CEMA in the urine of people who use these non-combusted products are extremely low, in contrast to cotinine., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prevalence of Helicobacter pylori ( H. pylori ) infection, the main risk factor for gastric cancer, has been decreasing in the United States; however, there remains a substantial racial disparity. Moreover, the time-trends for prevalence of CagA-positive H. pylori infection, the most virulent form, are unknown in the U.S., Population: We sought to assess prevalence of CagA-positive H. pylori infection over time by race in the United States., Methods: We utilized multiplex serology to quantify antibody responses to H. pylori antigens in 4,476 participants across five cohorts that sampled adults from 1985 to 2009. Using log-binomial regression models, we calculated prevalence ratios and 95% confidence intervals for the association between H. pylori -CagA sero-prevalence and birth year by race., Results: African Americans were three times more likely to be H. pylori -CagA sero-positive than Whites. After adjustment, H. pylori -CagA sero-prevalence was lower with increasing birth year among Whites ( P trend = 0.001), but remained stable for African Americans. When stratified by sex and education separately, the decline in H. pylori -CagA sero-positivity among Whites remained only for females ( P trend < 0.001) and was independent of educational attainment. Among African Americans, there was no difference by sex; furthermore, sero-prevalence increased with increasing birth year among those with a high school education or less ( P = 0.006)., Conclusions: Among individuals in the United States born from the 1920s to 1960s, H. pylori -CagA sero-prevalence has declined among Whites, but not among African Americans., Impact: Our findings suggest a widening racial disparity in the prevalence of the most virulent form of H. pylori , the main cause of gastric cancer., (©2020 American Association for Cancer Research.)

Background: Trends in diet quality among US adults indicate a steady improvement, but data on longitudinal individual-level changes in diet quality are still limited., Objective: We examined changes in diet quality over 10 y and sought to determine whether baseline sociodemographic and lifestyle factors predicted the changes in a multiethnic population., Methods: Data were from 63,255 African American, Native Hawaiian, Japanese American, Latino, and white men and women (45-75 y old at baseline) in the Multiethnic Cohort, who completed a quantitative food frequency questionnaire at baseline (1993-1996) and 10-y follow-up (2003-2007) and had no prevalent cancer or heart disease at either survey. Overall diet quality was measured by use of the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet score, and the Dietary Approaches to Stop Hypertension (DASH) score. We used a general linear model with adjustment for covariates to compare diet quality changes by baseline characteristics in men and women separately., Results: Overall diet quality improved over 10 y by 3.2 points in men and 2.9 in women assessed using the HEI-2015, although scores for some components worsened (saturated and trans fats, indicating increased intake) or remained unchanged at a low quality level (whole grains, dairy, and sodium). In multivariable models where changes in HEI-2015, AHEI-2010, and DASH were harmonized to a 100-point score, greater increases in scores in both men and women were found for Japanese American ethnicity (increase by 0.5-4.7 in the 3 scores, P < 0.03), higher education (by 0.5-1.5, P ≤ 0.001), normal weight (BMI 18.5 to <25, by 0.6-2.5, P ≤ 0.01), nonsmoking (by 1.5-2.7, P < 0.001), higher moderate/vigorous physical activity level (by 0.3-0.8, P ≤ 0.04), and multivitamin use (by 0.4-0.7, P < 0.001) at baseline., Conclusions: Sociodemographic and lifestyle factors, closely associated with diet quality, also predicted subsequent changes in diet quality over time in this multiethnic population., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background and Aims: Epidemiological data on dietary risk factors for nonalcoholic fatty liver disease (NAFLD) from population-based studies, particularly in an ethnically diverse population, are scarce. We examined dietary factors in relation to NAFLD risk in African Americans, Japanese Americans, Latinos, native Hawaiians, and whites in the Multiethnic Cohort (MEC)., Approach and Results: A nested case-control analysis was conducted within the MEC, a large prospective study with >215,000 older adult participants in Hawaii and California. NAFLD was identified using Medicare claims data, and controls were selected among participants without liver disease and individually matched to cases by birth year, sex, ethnicity, and length of Medicare enrollment. Diet was assessed at baseline through a validated quantitative food frequency questionnaire. Diet-NAFLD associations were quantified by odds ratios and 95% confidence intervals using multivariable conditional logistic regression. The study consisted of 2,974 NAFLD cases (518 with cirrhosis, 2,456 without cirrhosis) and 29,474 matched controls. Red meat (P trend = 0.010), processed red meat (P trend = 0.004), poultry (P trend = 0.005), and cholesterol (P trend = 0.005) intakes were positively associated with NAFLD, while dietary fiber intake (P trend = 0.003) was inversely associated with risk. Stronger associations were observed between red meat and cholesterol and NAFLD with cirrhosis than without cirrhosis (P heterogeneity ≤0.014)., Conclusions: Dietary factors are independently associated with NAFLD and NAFLD-related cirrhosis in a multiethnic population. Decreasing the consumption of cholesterol, red and processed meat, and poultry and increasing consumption of fiber may reduce the risk for NAFLD and related advanced liver disease., (© 2019 by the American Association for the Study of Liver Diseases.)

The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45-75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993-1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S. minority groups. We performed genome-wide association analyses for four lipid traits in over 45,000 ancestrally diverse participants from the Population Architecture using Genomics and Epidemiology (PAGE) Study, followed by a meta-analysis with several European ancestry studies. We identified nine novel lipid loci, five of which showed evidence of replication in independent studies. Furthermore, we discovered one novel gene in a PrediXcan analysis, minority-specific independent signals at eight previously reported loci, and potential functional variants at two known loci through fine-mapping. Systematic examination of known lipid loci revealed smaller effect estimates in African American and Hispanic ancestry populations than those in Europeans, and better performance of polygenic risk scores based on minority-specific effect estimates. Our findings provide new insight into the genetic architecture of lipid traits and highlight the importance of conducting genetic studies in diverse populations in the era of precision medicine., Competing Interests: The authors have declared that no competing interests exist.

Objective: Lung cancer is increasingly recognised as a heterogeneous disease. Recent advances with targeted therapies for lung cancer with oncogenic mutations have greatly improved the prognosis for this subset of patients, yet little is known about their experiences. This study aimed to identify the needs and explore the healthcare experiences of these advanced patients with oncogenic mutation driven lung cancer., Design: Qualitative interviews with patients with advanced or metastatic non-small cell lung cancer with oncogenic alterations in anaplastic lymphoma kinase, epidermal growth factor receptor or c-ros oncogene 1., Settings: Patients were recruited from online lung cancer support groups within the USA. Interviews were conducted remotely or in person, transcribed verbatim and analysed using an iterative inductive and deductive process., Participants: We included 39 patients (11 males and 28 females) with a median age of 48., Results: Two primary theme categories emerged: patients' unmet needs and improving healthcare experiences. Unmet needs are related to patients' desire to view their disease as a chronic illness, aspire to live a meaningful existence without financial devastation, desire for understanding along with emotional support and needing help with practical matters. Improving healthcare experiences involved patients' desire to trust the expertise of clinical providers, receive reliable care and be treated holistically and as informed partners., Conclusions: Patients with lung cancer with oncogenic mutations live uncharted experiences. Targeted therapy brings hope, but uncertainty is daunting. Patients grapple with the meaning and purpose of their lives while day-to-day obligations remain challenging. Healthcare teams are instrumental in their care experiences, and patients desire providers who are up-to-date on advances in the field and treat them as whole persons., Competing Interests: Competing interests: MAA, L-MB, LM, MT and DR have no conflict of interest to report. LC received honoraria as a consultant for Amgen. She has also received research funding to institutions that she works with and/or serves on the advisory board for: Novartis, Merck, Lily/Imclone, Bristol Myers Squibb, AstraZeneca/Medimmune, Pfizer, Incyte, Takeda, VentiRx, Sanofi-Genzyme, Seattle Genetics, Dynavax, Genentech, Synthorx and Alkermes., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30 kg/m 2 (RR 1.25, 95% CI 1.08-1.46), current smoking (<20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry 1-3 . In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific 4-10 . Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations 11,12 . Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions 13 -the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.

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; p trend  = 0.01) and the frequency (≥4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; p trend  = 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; p trend  = 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.

Background & Aims: We compared fat storage in the abdominal region among individuals from 5 different ethnic-racial groups to determine whether fat storage is associated with disparities observed in metabolic syndrome and other obesity-associated diseases., Methods: We collected data from 1794 participants in the Multiethnic Cohort Study (60-77 years old; of African, European [white], Japanese, Latino, or Native Hawaiian ancestry) with body mass index values of 17.1-46.2 kg/m 2 . From May 2013 through April 2016, participants visited the study clinic to undergo body measurements, an interview, and a blood collection. Participants were evaluated by dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging. Among ethnic groups, we compared adiposity of the trunk, intra-abdominal visceral cavity, and liver, adjusting for total fat mass; we evaluated the association of adult weight change with abdominal adiposity; and we examined the prevalence of metabolic syndrome mediated by abdominal adiposity., Results: Relative amounts of trunk, visceral, and liver fat varied significantly with ethnicity-they were highest in Japanese Americans, lowest in African Americans, and intermediate in the other groups. Compared with African Americans, the mean visceral fat area was 45% and 73% greater in Japanese American men and women, respectively, and the mean measurements of liver fat were 61% and 122% greater in Japanese American men and women. The visceral and hepatic adiposity associated with weight gain since participants were 21 years old varied in a similar pattern among ethnic-racial groups. In the mediation analysis, visceral and liver fat jointly accounted for a statistically significant fraction of the difference in metabolic syndrome prevalence, compared with white persons, for African Americans, Japanese Americans, and Native Hawaiian women, independently of total fat mass., Conclusions: In an analysis of data from the participants in the Multiethnic Cohort Study, we found extensive differences among ethnic-racial groups in the propensity to store fat intra-abdominally. This observation should be considered by clinicians in the prevention and early detection of metabolic disorders., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States., Methods: We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression., Results: Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007)., Conclusions: In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Lung cancer is the leading cause of cancer-related death. While cigarette smoking is the primary cause of this malignancy, risk differs across racial/ethnic groups. For the same number of cigarettes smoked, Native Hawaiians compared to whites are at greater risk and Japanese Americans are at lower risk of developing lung cancer. DNA methylation of specific CpG sites (e.g., in AHRR and F2RL3) is the most common blood epigenetic modification associated with smoking status. However, the influence of internal smoking dose, measured by urinary nicotine equivalents (NE), on DNA methylation in current smokers has not been investigated, nor has a study evaluated whether for the same smoking dose, circulating leukocyte DNA methylation patterns differ by race., Methods: We conducted an epigenome-wide association study (EWAS) of NE in 612 smokers from three racial/ethnic groups: whites (n = 204), Native Hawaiians (n = 205), and Japanese Americans (n = 203). Genome-wide DNA methylation profiling of blood leukocyte DNA was measured using the Illumina 450K BeadChip array. Average β value, the ratio of signal from a methylated probe relative to the sum of the methylated and unmethylated probes at that CpG, was the dependent variables in linear regression models adjusting for age, sex, race (for pan-ethnic analysis), and estimated cell-type distribution., Results: We found that NE was significantly associated with six differentially methylated CpG sites (Bonferroni corrected p < 1.48 × 10-7): four in or near the FOXK2, PBX1, FNDC7, and FUBP3 genes and two in non-annotated genetic regions. Higher levels of NE were associated with increasing methylation beta-valuesin all six sites. For all six CpG sites, the association was only observed in Native Hawaiians, suggesting that the influence of smoking dose on DNA methylation patterns is heterogeneous across race/ethnicity (p interactions < 8.8 × 10-8). We found two additional CpG sites associated with NE in only Native Hawaiians., Conclusions: In conclusion, internal smoking dose was associated with increased DNA methylation in circulating leukocytes at specific sites in Native Hawaiian smokers but not in white or Japanese American smokers.

Background & Aims: Healthy eating patterns assessed by diet quality indexes (DQIs) have been related to lower risk of colorectal cancer-mostly among whites. We investigated the associations between 4 DQI scores (the Healthy Eating Index 2010 [HEI-2010], the Alternative Healthy Eating Index 2010 [AHEI-2010], the alternate Mediterranean diet score [aMED], and the Dietary Approaches to Stop Hypertension score) and colorectal cancer risk in the Multiethnic Cohort., Methods: We analyzed data from 190,949 African American, Native Hawaiian, Japanese American, Latino, and white individuals, 45 to 75 years old, who entered the Multiethnic Cohort study from 1993 through 1996. During an average 16 years of follow-up, 4770 invasive colorectal cancer cases were identified., Results: Scores from all 4 DQIs associated inversely with colorectal cancer risk; higher scores associated with decreasing colorectal cancer risk (all P's for trend ≤ .003). Associations were not significant for AHEI-2010 and aMED scores in women after adjustment for covariates: for the highest vs lowest quintiles, the hazard ratio for the HEI-2010 score in men was 0.69 (95% confidence interval [CI], 0.59-0.80) and in women was 0.82 (95% CI, 0.70-0.96); for the AHEI-2010 score the hazard ratio in men was 0.75 (95% CI, 0.65-0.85) and in women was 0.90 (95% CI, 0.78-1.04); for the aMED score the hazard ratio in men was 0.84 (95% CI, 0.73-0.97) and in women was 0.96 (95% CI, 0.82-1.13); for the Dietary Approaches to Stop Hypertension score the hazard ratio in men was 0.75 (95% CI, 0.66-0.86) and in women was 0.86 (95% CI, 0.75-1.00). Associations were limited to the left colon and rectum for all indexes. The inverse associations were less strong in African American individuals than in the other 4 racial/ethnic groups., Conclusions: Based on an analysis of data from the Multiethnic Cohort Study, high-quality diets are associated with a lower risk of colorectal cancer in most racial/ethnic subgroups., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA) was designed to substantially improve fine-mapping and functional discovery by increasing variant coverage across multiple ethnicities at known loci for metabolic, cardiovascular, renal, inflammatory, anthropometric, and a variety of lifestyle traits. Studying the frequency distribution of clinically relevant mutations, putative risk alleles, and known functional variants across multiple populations will provide important insight into the genetic architecture of complex diseases and facilitate the discovery of novel, sometimes population-specific, disease associations. DNA samples from 51,650 self-identified African ancestry (17,328), Hispanic/Latino (22,379), Asian/Pacific Islander (8,640), and American Indian (653) and an additional 2,650 participants of either South Asian or European ancestry, and other reference panels have been genotyped on MEGA by PAGE II. MEGA was designed as a new resource for studying ancestrally diverse populations. Here, we describe the methodology for selecting trait-specific content for use in multi-ethnic populations and how enriching MEGA for this content may contribute to deeper biological understanding of the genetic etiology of complex disease., Competing Interests: The authors have declared that no competing interests exist.

Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%)., Conclusions: We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969-1977)., Competing Interests: the authors disclose no conflicts, (© 2016 by the American Association for the Study of Liver Diseases.)

Importance: An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention., Objective: To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors., Design, Setting, and Participants: Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality., Exposures: Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors., Main Outcomes and Measures: Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking)., Results: The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population., Conclusions and Relevance: This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.

Background: Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are major causes of morbidity and mortality among Hispanics. Disparities in the incidence of HCC and in CLD deaths by nativity in Hispanics have been reported. Whether individual-level risk factors could explain these disparities was assessed in a prospective study of 36,864 Hispanics (18,485 US-born and 18,379 foreign-born) in the Multiethnic Cohort., Methods: Risk factors were assessed with a baseline questionnaire and Medicare claim files. During a 19.6-year follow-up, 189 incident cases of HCC and 298 CLD deaths were identified., Results: The HCC incidence rate was almost twice as high for US-born Hispanic men versus foreign-born Hispanic men (44.7 vs 23.1), but the rates were comparable for women (14.5 vs 13.4). The CLD mortality rate was about twice as high for US-born Hispanics versus foreign-born Hispanics (66.3 vs 35.1 for men and 42.2 vs 19.7 for women). Heavy alcohol consumption was associated with HCC and CLD in foreign-born individuals, whereas the current smoking status, hepatitis B/C viral infection, and diabetes were associated with both HCC and CLD. After adjustments for these risk factors, the hazard rate ratios for HCC and CLD death were 1.58 (95% confidence interval, 1.00-2.51) and 1.85 (95% confidence interval, 1.25-2.73), respectively, for US-born Hispanics versus foreign-born Hispanics., Conclusions: US-born Hispanics, particularly males, are at greater risk for HCC and death from CLD than foreign-born Hispanics. Overall known differences in risk factors do not account for these disparities. Future studies are warranted to identify factors that contribute to the elevated risk of HCC development and CLD death in US-born Hispanics. Cancer 2016;122:1444-1452. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P's ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; Ptrend = 8.0×10-5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.

Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6 and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age-specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6 fold (95% CI: 2.3-13.8; p = 0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9-10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0-46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p = 0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome., (© 2015 UICC.)

Background: Physical therapists' perceptions of sexual boundaries in clinic settings in the United States have not been studied. Given the magnitude of potential consequences of sexual boundary violations, examination of this topic is imperative., Objective: The purpose of this study was to describe the perceptions of sexual boundaries among licensed physical therapists in the United States., Methods: Licensed physical therapists from Arkansas, Kansas, Maine, Ohio, and Oregon were contacted by email and asked to complete a sexual boundaries questionnaire via Survey Monkey™; 967 surveys (7.3%) were returned., Results: While most physical therapists practice within the profession's Code of Ethics, there are practitioners who date current and former patients, and condone patients' sexual banter in the clinic. Almost half (42%) of the participants acknowledged feeling sexually attracted to a patient. While gender differences were seen throughout the analyses, generally, the demographic and professional variables did not account for meaningful variance. Results were similar to previous research on physiotherapists in other countries., Conclusions: Sexuality is part of the physical therapy practice environment and physical therapists' understanding of sexual boundaries is ambiguous. These data can inform professional conversation on sexual boundaries in physical therapy practice leading to greater understanding and decreased potential for violations.

Background: Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 causes a high risk of colorectal and other cancers (Lynch Syndrome). Use of aspirin has been shown to be associated with a reduced risk of colorectal cancer for the general population as well as for MMR gene mutation carriers. The aim of this study was to determine whether use of aspirin and ibuprofen in a nontrial setting is associated with the risk of colorectal cancer risk for MMR gene mutation carriers., Methods: We included 1858 participants in the Colon Cancer Family Registry who had been found to have a pathogenic germline mutation in a MMR gene (carriers). We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided., Results: A total of 714 carriers (38%) were diagnosed with colorectal cancer at a mean age of 42.4 (standard deviation 10.6) years. A reduced risk of colorectal cancer was associated with aspirin use (for 1 month to 4.9 years: HR = 0.49, 95% CI = 0.27 to 0.90, P = .02; for ≥5 years: HR = 0.25, 95% CI = 0.10 to 0.62, P = .003) and ibuprofen use (for 1 month to 4.9 years: HR = 0.38, 95% CI = 0.18 to 0.79, P = .009; for ≥5 years: HR = 0.26, 95% CI = 0.10 to 0.69, P = .007), compared with less than one month of use., Conclusion: Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P(trend) < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (P(trend) = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (P(trend) = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)