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Background: Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a decreased colorectal cancer (CRC) risk. However, to the best of the authors' knowledge, the effects of NSAID on clinical outcomes after CRC diagnosis are not well defined. The authors investigated the association between prediagnosis NSAID use and mortality after CRC diagnosis among women in the California Teachers Study cohort.Methods: Women aged <85 years participating in the California Teachers Study, without a prior CRC diagnosis at baseline (1995-1996), and who were diagnosed with CRC during follow-up through December 2005, were eligible for analysis of the association between prediagnosis NSAID use and mortality. NSAID use (including aspirin and ibuprofen) was collected through a self-administered questionnaire. Cancer occurrence was identified through California Cancer Registry linkage. Multivariate Cox proportional hazards regression models were used to estimate hazards ratios (HR) for death and 95% confidence intervals (95% CIs).Results: Among 621 CRC patients who were identified, 64% reported no prediagnosis regular NSAID use, 17% reported use of 1 to 6 days/week, and 20% reported daily use. A duration of NSAID use <5 years was reported by 17% of patients and a use of >or=5 years was reported by 18%. Regular prediagnosis NSAID use (1-3 days/week, 4-6 days/week, and daily) versus none was associated with improved overall survival (OS) (HR, 0.71; 95% CI, 0.53-0.95) and CRC-specific survival (HR, 0.58; 95% CI 0.40-0.84) after adjustment for clinically relevant factors. Prediagnosis NSAID use >or=5 years (vs none) was found to be associated with improved OS (HR, 0.55; 95% CI, 0.37-0.84) and CRC-specific survival (HR, 0.40; 95% CI, 0.23-0.71) in adjusted analyses.Conclusions: When used regularly or over a prolonged duration before CRC diagnosis, NSAIDs are associated with decreased mortality among female CRC patients. [ABSTRACT FROM AUTHOR]

High intakes of calcium and dairy products have been suggested to be related to prostate cancer risk. Such associations were examined in the Multiethnic Cohort Study (1993-2002) among 82,483 men who completed a detailed quantitative food frequency questionnaire. During a mean follow-up of 8 years, 4,404 total cases of prostate cancer were identified. In Cox proportional hazards models, no association was found between calcium and vitamin D intake and total, advanced, or high-grade prostate cancer risk, whether for total intake, intake from foods, or intake from supplements, among all male participants or among nonusers of supplemental calcium. No association of calcium or vitamin D intake was seen across racial/ethnic groups. In analyses of food groups, dairy product and total milk consumption were not associated with prostate cancer risk. However, low-/nonfat milk was related to an increased risk and whole milk to a decreased risk of total prostate cancer; after stratification, these effects were limited to localized or low-grade tumors. Although the findings from this study do not support an association between the intakes of calcium and vitamin D and prostate cancer risk, they do suggest that an association with milk consumption may vary by fat content, particularly for early forms of this cancer. [ABSTRACT FROM AUTHOR]

The association of body size, lifestyle, and medical conditions with renal cell cancer risk was examined among 161,126 Hawaii-Los Angeles Multiethnic Cohort participants (1993-2002). After 8.3 years of follow-up, 347 renal cell cancer cases (220 men, 127 women) were identified. Renal cell cancer risk increased with increasing body mass index in men (multivariate relative risk (RR) = 1.06 per unit of body mass index, p = 0.001) and women (RR = 1.07, p < 0.0001). The relative risks associated with being obese compared with being lean were 1.76 (95% confidence interval (CI): 1.20, 2.58) for men and 2.27 (95% CI: 1.37, 3.74) for women. Hypertension was associated with renal cell cancer (RR(men) = 1.42, 95% CI: 1.07, 1.87; RR(women) = 1.58, 95% CI: 1.09, 2.28). Smoking was confirmed to be a risk factor for both sexes. Among women, diuretic use was associated with increased risk (RR = 1.63, 95% CI: 1.04, 2.57), whereas physical activity was associated with reduced risk (p(trend) = 0.027). Alcohol consumption was inversely associated with risk for men (p(trend) = 0.045). Compared with nondrinkers, men who drank >/=1 drinks/day had a 31% lower risk (95% CI: 0.49, 0.96). Results show that body mass index, smoking, and hypertension are risk factors for renal cell cancer in both sexes. [ABSTRACT FROM AUTHOR]

Diet may be a modifier of smoking-related cancer risk, with protective effects of intake of fruits and vegetables and associated antioxidants found in many observational studies. We previously reported serum Beta-Cryptoxanthin levels being inversely associated with smoking-related lung cancer incidence in a cohort of Chinese men. We noted, however, that serum Beta-Cryptoxanthinn is negatively correlated with smoking. Since self-reports of smoking intensity undoubtedly contain errors, this negative correlation indicates a potential bias in assessing the effects of Beta-Cryptoxanthin, due to confounding with the unmeasured (residual) portion of cigarette exposure. We evaluated cotinine levels in pre-diagnostic spot urine samples to attempt to improve smoking assessment. We noted that urinary cotinine levels correlated significantly with cigarette consumption overall and that cotinine was strongly predictive of lung cancer risk. Urinary cotinine, however, was not as strong a predictor of lung cancer risk in current smokers as were self-reports of cigarette consumption and cotinine remained only a marginally significant predictor of lung cancer risk after adjustment for self-reports. An apparent benefit of Beta-Cryptoxanthin remained evident when including both urinary cotinine and self-reported cigarette consumption and cotinine in the statistical model. However, we conclude that cotinine measured from a single spot urine seems to have only limited value in augmenting self-reports of cigarette consumption so that, at present, the apparent protective effects of Beta-Cryptoxanthinn, as seen in our own study, should continue to be regarded as unproven. We believe that future epidemiological evaluation of the association between Beta-Cryptoxanthin (and other antioxidants) and reduced lung cancer risk must utilize improved biomarkers to augment smokers' own self-reports of smoking amount. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low intake of dietary fat and high intake of soy foods have been suggested to partly explain the lower breast cancer rates in Asia, perhaps because of lower endogenous estrogens. OBJECTIVE: The objective was to assess the hormonal and nonhormonal effects of diets resembling an Asian diet in terms of total fat and soy food contents. DESIGN: Fifty-seven postmenopausal women participated in a randomized, controlled, dietary intervention study. The subjects consumed a very-low-fat diet (VLFD; 11% of energy as fat), a Step I diet (25% of energy as fat) supplemented with soy food (SFD; 50 mg isoflavones/d), or a control Step I diet (CD; 27% of energy as fat) with no soy food. All diets were prepared at the General Clinical Research Center of the University of Southern California. Serum hormones and other markers were measured at baseline and every 2 wk during the 8 wk of intervention. RESULTS: There were no significant differences in total estradiol and sex hormone binding globulin at the completion of the intervention between women in the SFD and VLFD groups and those in the CD group. Serum insulin decreased significantly in the SFD group, and leptin decreased significantly in the SFD and VLFD groups; however, these changes did not differ significantly from the changes in the CD group. CONCLUSIONS: This study does not provide evidence that ingestion of soy food or a VLFD significantly reduces estrogen concentrations in postmenopausal women. However, short-term changes in diet may have significant and beneficial effects on blood insulin and leptin concentrations. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Studies of migrants, along with geographic and temporal variations in incidence, indicate that colorectal cancer is especially sensitive to changes in environmental factors, including, most importantly, diet. The goal of this research was to examine the changes in dietary practices that may be consistent with the changing incidence of colorectal cancer in the Los Angeles Mexican-American population. Cancer incidence and dietary intake data were available for over 35,000 Latinos of Mexican national origin currently participating in the prospective Multiethnic Cohort Study, representing the largest sample of Mexican-origin Latinos of any such study in the United States. The dataset is unique in that changes in cancer rates and in dietary behaviors across three generations could be examined. Most of the change in colorectal cancer rates occurred between the first and second generations, and, correspondingly, nearly all the dietary change also occurred between the first and second generations. Although some food traditions were retained by Mexican Americans, the dietary changes due to acculturation were significant and support an association between colorectal cancer risk and certain dietary components, notably, alcohol as a risk factor and nonstarch polysaccharides and vegetables as protective factors. [ABSTRACT FROM AUTHOR]

This report describes the development and validation/calibration of a structured food frequency questionnaire for use in a large-scale cohort study of diet and health in Chinese men and women aged 45-74 years in Singapore, the development of a food composition database for analysis of the dietary data, and the results of the dietary validation/calibration study. The present calibration study comparing estimated intakes from 24-hour recalls with those from the food frequency questionnaires revealed correlations of 0.24-0.79 for energy and nutrients among the Singapore Chinese, which are comparable to the correlation coefficients reported in calibration studies of other populations. We also report on the nutritional profiles of Singapore Chinese on the basis of results of 1,880 24-hour dietary recalls conducted on 1,022 (425 men and 597 women) cohort subjects. Comparisons with age-adjusted corresponding values for US whites and blacks show distinct differences in dietary intakes between the Singapore and US populations. The Singapore cohort will be followed prospectively to identify dietary associations with cancer risk and other health outcomes. [ABSTRACT FROM AUTHOR]

Background: There is compelling evidence that estrogens influence breast cancer risk. Since the mid-1980s, dietary fat intervention studies have been conducted to investigate the effect of fat intake on endogenous estrogen levels. To further our understanding of the possible relationship between dietary fat and breast cancer, we conducted a meta-analysis of dietary fat intervention studies that investigated serum estradiol levels, and we reviewed the nature of the evidence provided by prospective analytic studies of fat consumption and breast cancer risk.Methods: A computerized search of the English language literature on estrogen/estradiol and dietary fat intervention studies published from January 1966 through June 1998 was conducted using the MEDLINE database. Pooled estimates were derived from the change in estradiol levels associated with fat reduction from 13 studies. Analyses were conducted separately for premenopausal and postmenopausal women and in both groups combined.Results and Conclusions: Statistically significant reductions in serum estradiol levels of -7.4% (95% confidence interval [CI] = -11.7% to -2.9%) among premenopausal women and -23.0% (95% CI = -27.7% to -18.1%) among postmenopausal women were observed, with an overall -13.4% (95% CI = -16.6% to -10.1%) reduction observed. The greatest reductions occurred in two studies in which dietary fat was reduced to 10%-12% of calories compared with 18%-25% of calories in the other studies. A statistically significant reduction in estradiol levels of -6.6% (95% CI = -10.3% to -2.7%) remained after exclusion of these two studies. Review of prospective analytic epidemiologic studies that allowed for dietary measurement error suggests that the possibility that reducing fat consumption below 20% of calories will reduce breast cancer risk cannot be excluded.Implications: Dietary fat reduction can result in a lowering of serum estradiol levels and such dietary modification may still offer an approach to breast cancer prevention. [ABSTRACT FROM AUTHOR]

Purpose: There are complex and paradoxical patterns in lung cancer incidence by race/ethnicity and gender; compared to non-Hispanic White (NHW) males, non-Hispanic Black (NHB) males smoke fewer cigarettes per day and less frequently but have higher lung cancer rates. Similarly, NHB females are less likely to smoke but have comparable lung cancer rates to NHW females. We use a multistage carcinogenesis model to study the impact of smoking on lung cancer incidence in NHB and NHW individuals in the Multiethnic Cohort Study (MEC)., Methods: The effects of smoking on the rates of lung tumor initiation, promotion, and malignant conversion, and the incidence of lung cancer in NHB versus NHW adults in the MEC were analyzed using the Two-Stage Clonal Expansion (TSCE) model. Maximum likelihood methods were used to estimate model parameters and assess differences by race/ethnicity, gender, and smoking history., Results: Smoking increased promotion and malignant conversion but did not affect tumor initiation. Non-smoking-related initiation, promotion, and malignant conversion and smoking-related promotion and malignant conversion differed by race/ethnicity and gender. Non-smoking-related initiation and malignant conversion were higher in NHB than NHW individuals, whereas promotion was lower in NHB individuals., Conclusion: Findings suggest that while smoking plays an important role in lung cancer risk, background risk not dependent on smoking also plays a significant and under-recognized role in explaining race/ethnicity differences. Ultimately, the resulting TSCE model will inform race/ethnicity-specific lung cancer natural history models to assess the impact of preventive interventions on US lung cancer outcomes and disparities by race/ethnicity., Competing Interests: Declarations Competing Interests The authors declare no competing interests. Ethics Approval This study was approved by the University of Michigan IRB (HUM00195762). Consent to Participate Informed consent was obtained from all MEC study participants., (© 2024. The Author(s).)

Purpose: Recent studies suggested fine particulate matter (PM 2.5 ) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse., Materials and Methods: Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors., Results: Satellite-based PM 2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m 3 , 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM 2.5 -associations ( P heterogeneity = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM 2.5 (HR per 10 μg/m 3 increase, 1.05 [95% CI, 1.00 to 1.10]; P = .064)., Conclusion: Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM 2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM 2.5 exposure.

Background: After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans., Methods: In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk., Results: TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10-1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03-1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL., Conclusions: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years., Impact: Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk., (©2024 American Association for Cancer Research.)

Background: A growing literature has reported associations between traffic-related air pollution and breast cancer, however there are fewer investigations into specific ambient agents and any putative risk of breast cancer development, particularly studies occurring in populations residing in higher pollution areas such as Los Angeles., Objectives: To estimate breast cancer risks related to ambient air toxics exposure at residential addresses., Methods: We examined the relationships between ambient air toxics and breast cancer risk in the Multiethnic Cohort among 48,665 California female participants followed for cancer from 2003 through 2013. We obtained exposure data on chemicals acting as endocrine disruptors or mammary gland carcinogens from the National-Scale Air Toxics Assessment. Cox proportional hazards models were used to estimate breast cancer risk per one interquartile range (IQR) increase in air toxics exposure lagged by 5-years. Stratified analyses were conducted by race, ethnicity, and hormone receptor types., Results: Among all women, increased risks of invasive breast cancer were observed with toxicants related to industries [1,1,2,2-tetrachloroethane (hazard ratio [HR] = 4.22, 95% confidence interval [95% CI] 3.18-5.60), ethylene dichloride (HR = 2.81, 95% CI 2.20-3.59), and vinyl chloride (HR = 2.27, 95% CI 1.81, 2.85); these 3 agents were correlated (r2 = 0.45-0.77)]. Agents related to gasoline production or combustion were related to increased breast cancer risk [benzene (HR = 1.32, 95% CI 1.24, 1.41), ethylbenzene (HR = 1.20, 95% CI 1.13-1.28), toluene (HR = 1.29, 95% CI 1.20-1.38), naphthalene (HR = 1.11, 95% CI 1.02-2.22), acrolein (HR = 2.26, 95% CI 1.92, 2.65)]. Higher hazard ratios were observed in African Americans and Whites compared to other racial and ethnic groups (p-heterogeneity <0.05 for traffic-related air toxics, acrolein, and vinyl acetate)., Conclusions: Our findings suggest that specific toxic air pollutants may be associated with increase breast cancer risk., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Ultrafine particles (UFP) are unregulated air pollutants abundant in aviation exhaust. Emerging evidence suggests that UFPs may impact lung health due to their high surface area-to-mass ratio and deep penetration into airways. This study aimed to assess long-term exposure to airport-related UFPs and lung cancer incidence in a multiethnic population in Los Angeles County., Methods: Within the California Multiethnic Cohort, we examined the association between long-term exposure to airport-related UFPs and lung cancer incidence. Multivariable Cox proportional hazards regression models were used to estimate the effect of UFP exposure on lung cancer incidence. Subgroup analyses by demographics, histology and smoking status were conducted., Results: Airport-related UFP exposure was not associated with lung cancer risk [per one IGR HR, 1.01; 95% confidence interval (CI), 0.97-1.05] overall and across race/ethnicity. A suggestive positive association was observed between a one IQR increase in UFP exposure and lung squamous cell carcinoma (SCC) risk (HR, 1.08; 95% CI, 1.00-1.17) with a Phet for histology = 0.05. Positive associations were observed in 5-year lag analysis for SCC (HR, 1.12; 95% CI, CI, 1.02-1.22) and large cell carcinoma risk (HR, 1.23; 95% CI, 1.01-1.49) with a Phet for histology = 0.01., Conclusions: This large prospective cohort analysis suggests a potential association between airport-related UFP exposure and specific lung histologies. The findings align with research indicating that UFPs found in aviation exhaust may induce inflammatory and oxidative injury leading to SCC., Impact: These results highlight the potential role of airport-related UFP exposure in the development of lung SCC., (©2024 American Association for Cancer Research.)

Background: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs., Methods: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG)., Results: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16)., Conclusion: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Approximately 10% of smokers will develop lung cancer. Sensitive predictive biomarkers are needed to identify susceptible individuals. 1,3-Butadiene (BD) is among the most abundant tobacco smoke carcinogens. BD is metabolically activated to 3,4-epoxy-1-butene (EB), which is detoxified via the glutathione conjugation/mercapturic acid pathway to form monohydroxybutenyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA). Alternatively, EB can react with guanine nucleobases of DNA to form N7-(1-hydroxyl-3-buten-1-yl) guanine (EB-GII) adducts. We employed isotope dilution LC/ESI-HRMS/MS methodologies to quantify MHBMA, DHBMA, and EB-GII in urine of smokers who developed lung cancer ( N = 260) and matched smoking controls ( N = 259) from the Southern Community Cohort (white and African American). The concentrations of all three biomarkers were significantly higher in smokers that subsequently developed lung cancer as compared to matched smoker controls after adjusting for age, sex, and race/ethnicity ( p < 0.0001 for EB-GII, p < 0.0001 for MHBMA, and p = 0.0007 for DHBMA). The odds ratio (OR) for lung cancer development was 1.63 for MHBMA, 1.37 for DHBMA, and 1.97 for EB-GII, with a higher OR in African American subjects than in whites. The association of urinary EB-GII, MHBMA, and DHBMA with lung cancer status did not remain upon adjustment for total nicotine equivalents. These findings reveal that urinary MHBMA, DHBMA, and EB-GII are directly correlated with the BD dose delivered via smoking and are associated with lung cancer risk.

Metabolic syndrome (MetS) is associated with a high risk of cardiovascular disease, a leading cause of death among women. MetS is a diagnosis of at least 3 of the following: high blood pressure, high fasting glucose, high triglycerides, high waist circumference, and low high-density lipoprotein cholesterol. Epidemiological studies suggest that endocrine disrupting chemical (EDC) exposure is positively associated with individual components of MetS, but evidence of an association between EDCs and MetS remains inconsistent. In a cross-sectional analysis within the Multiethnic Cohort Study, we evaluated the association between 4 classes of urinary EDCs (bisphenol A [BPA], triclosan, parabens, and phthalates) and MetS among 1728 women. Multivariable logistic regression was used to estimate odds ratios and 95% CI for the association between tertiles of each EDC and MetS adjusting for age, body mass index (BMI), racial and ethnic group, and breast cancer status. Stratified analyses by race and ethnicity and BMI were conducted. MetS was identified in 519 (30.0%) women. We did not detect statistically significant associations of MetS with BPA, triclosan, or phthalate metabolite excretion. MetS was inversely associated with total parabens ( P trend = .002). Although there were suggestive inverse associations between EDCs and MetS among Latino and African American women, and women with BMI < 30 kg/m 2 , there was no statistically significant heterogeneity in associations by race and ethnicity or BMI. These findings suggest an inverse association between parabens and MetS in larger multiethnic studies. Prospective analyses to investigate suggested differences in associations by race, ethnicity, and BMI are warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Importance: Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC., Objective: To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked., Design, Setting, and Participants: This population-based prospective cohort study used data from the Multiethnic Cohort Study (MEC), which enrolled participants between April 18, 1993, and December 31, 1996, with follow-up through July 1, 2017. Eligible individuals for this study were aged 45 to 75 years and had complete smoking data at baseline. These participants were followed up for IPLC and further SPLC development through the Surveillance, Epidemiology, and End Results registry. The data were analyzed from July 1, 2022, to January 31, 2023., Exposures: Never-smoking vs ever-smoking exposure at MEC enrollment., Main Outcomes and Measures: The study had 2 primary outcomes: (1) 10-year cumulative incidence of IPLC in the entire study cohort and 10-year cumulative incidence of SPLC among patients with IPLC and (2) standardized incidence ratio (SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by smoking history., Results: Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over 4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years. Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6 (7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers, which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%). However, the 10-year cumulative SPLC incidence following IPLC was as high among never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI, 2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50; 95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12)., Conclusions and Relevance: The findings indicate that SPLC risk among lung cancer survivors who never smoked is as high as among those with IPLC who ever-smoked, highlighting the need to identify risk factors for SPLC among patients who never smoked and to develop a targeted surveillance strategy.

Inhaled particles and gases can harm health by promoting chronic inflammation in the body. Few studies have investigated the relationship between outdoor air pollution and inflammation by race and ethnicity, socioeconomic status, and lifestyle risk factors. We examined associations of particulate matter (PM) and other markers of traffic-related air pollution with circulating levels of C-reactive protein (CRP), a biomarker of systemic inflammation. CRP was measured from blood samples obtained in 1994-2016 from 7,860 California residents participating in the Multiethnic Cohort (MEC) Study. Exposure to PM (aerodynamic diameter ≤2.5 μm [PM 2.5 ], ≤10 μm [PM 10 ], and between 2.5 and 10 μm [PM 10-2.5 ]), nitrogen oxides (NO x , including nitrogen dioxide [NO 2 ]), carbon monoxide (CO), ground-level ozone (O 3 ), and benzene averaged over one or twelve months before blood draw were estimated based on participants' addresses. Percent change in geometric mean CRP levels and 95% confidence intervals (CI) per standard concentration increase of each pollutant were estimated using multivariable generalized linear regression. Among 4,305 females (55%) and 3,555 males (45%) (mean age 68.1 [SD 7.5] years at blood draw), CRP levels increased with 12-month exposure to PM 10 (11.0%, 95% CI: 4.2%, 18.2% per 10 μg/m 3 ), PM 10-2.5 (12.4%, 95% CI: 1.4%, 24.5% per 10 μg/m 3 ), NO x (10.4%, 95% CI: 2.2%, 19.2% per 50 ppb), and benzene (2.9%, 95% CI: 1.1%, 4.6% per 1 ppb). In subgroup analyses, these associations were observed in Latino participants, those who lived in low socioeconomic neighborhoods, overweight or obese participants, and never or former smokers. No consistent patterns were found for 1-month pollutant exposures. This investigation identified associations of primarily traffic-related air pollutants, including PM, NO x , and benzene, with CRP in a multiethnic population. The diversity of the MEC across demographic, socioeconomic, and lifestyle factors allowed us to explore the generalizability of the effects of air pollution on inflammation across subgroups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Frailty status has been sparsely studied in some groups including Native Hawaiians and Asian Americans., Methods: We developed a questionnaire-based deficit accumulation frailty index (FI) in the Multiethnic Cohort (MEC) and examined frailty status (robust, FI 0 to <0.2, prefrail, FI 0.2 to <0.35, and frail FI ≥ 0.35) among 29 026 men and 40 756 women., Results: After adjustment for age, demographic, lifestyle factors, and chronic conditions, relative to White men, odds of being frail was significantly higher (34%-54%) among African American, Native Hawaiian, and other Asian American men, whereas odds was significantly lower (36%) in Japanese American men and did not differ in Latino men. However, among men who had high school or less, none of the groups displayed significantly higher odds of prefrail or frail compared with White men. Relative to White women, odds of being frail were significantly higher (14%-33%) in African American and Latino women, did not differ for other Asian American women and lower (14%-36%) in Native Hawaiian and Japanese American women. These racial and ethnic differences in women were observed irrespective of education. Risk of all-cause mortality was higher in prefrail and frail men than robust men (adjusted hazard ratio [HR] = 1.69, 1.59-1.81; HR = 3.27, 3.03-3.53); results were similar in women. All-cause mortality was significantly positively associated with frailty status and frailty score across all sex, race, and ethnic groups., Conclusions: Frailty status differed significantly by race and ethnicity and was consistently associated with all-cause mortality. The FI may be a useful tool for aging studies in this multiethnic population., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: While cigarette smoking is the leading cause of lung cancer, the majority of smokers do not develop the disease over their lifetime. The inter-individual differences in risk among smokers may in part be due to variations in exposure to smoking-related toxicants., Methods: Using data from a subcohort of 2,309 current smokers at the time of urine collection from the Multiethnic Cohort Study, we prospectively evaluated the association of ten urinary biomarkers of smoking-related toxicants [total nicotine equivalents (TNE), a ratio of total trans-3'-hydroxycotinine (3-HCOT)/cotinine (a phenotypic measure of CYP2A6 enzymatic activity), 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), S-phenylmercapturic acid (SPMA), 3-hydroxypropyl mercapturic acid (3-HPMA), phenanthrene tetraol (PheT), 3-hydroxyphenanthrene (PheOH), the ratio of PheT/PheOH, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid (8-iso-PGF2α)] with lung cancer risk (n = 140 incident lung cancer cases over an average of 13.4 years of follow-up). Lung cancer risk was estimated using Cox proportional hazards models., Results: After adjusting for decade of birth, sex, race/ethnicity, body mass index, self-reported pack-years, creatinine, and urinary TNE (a biomarker of internal smoking dose), a one SD increase in log total 3-HCOT/cotinine (HR, 1.33; 95% CI, 1.06-1.66), 3-HPMA (HR, 1.41; 95% CI, 1.07-1.85), and Cd (HR, 1.45; 95% CI, 1.18-1.79) were each associated with increased lung cancer risk., Conclusions: Our study demonstrates that urinary total 3-HCOT/cotinine, 3-HPMA, and Cd are positively associated with lung cancer risk. These findings warrant replication and consideration as potential biomarkers for smoking-related lung cancer risk., Impact: These biomarkers may provide additional information on lung cancer risk that is not captured by self-reported smoking history or TNE. See related commentary by Etemadi et al., p. 289., (©2022 American Association for Cancer Research.)

Background: Data on diet quality and pancreatic cancer are limited. We examined the relationship between diet quality, assessed by 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 energy-adjusted Dietary Inflammatory Index (E-DII), and pancreatic cancer incidence in the Multiethnic Cohort Study., Methods: Diet quality scores were calculated from a validated food frequency questionnaire administered at baseline. Cox models were used to calculate HR and 95% confidence intervals (CI) adjusted for age, sex, race/ethnicity, education, diabetes, family history of pancreatic cancer, physical activity, smoking variables, total energy intake, body mass index (BMI), and alcohol consumption. Stratified analyses by sex, race/ethnicity, smoking status, and BMI were conducted., Results: Over an average follow-up of 19.3 years, 1,779 incident pancreatic cancer cases were identified among 177,313 participants (average age of 60.2 years at baseline, 1993-1996). Overall, we did not observe associations between the dietary pattern scores and pancreatic cancer (aMED: 0.98; 95% CI, 0.83-1.16; HEI-2015: 1.03; 95% CI, 0.88-1.21; AHEI-2010: 1.03; 95% CI, 0.88-1.20; DASH: 0.92; 95% CI, 0.79-1.08; E-DII: 1.05; 95% CI, 0.89-1.23). An inverse association was observed with DASH for ever smokers (HR, 0.75; 0.61-0.93), but not for nonsmokers (HR, 1.05; 0.83-1.32)., Conclusions: The DASH diet showed an inverse association with pancreatic cancer among ever smokers, but does not show a protective association overall., Impact: Modifiable measures are needed to reduce pancreatic cancer burden in these high-risk populations; our study adds to the discussion of the benefit of dietary changes., (©2022 American Association for Cancer Research.)

Few studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of the percent visceral adiposity tissue (VAT) area out of the overall abdominal area, averaged across L1-L5 (%VAT), measured by abdominal magnetic resonance imaging (MRI). A genome-wide significant signal was found on chromosome 2q14.3 in the sex-combined GWAS (lead variant rs79837492: Beta per effect allele = -4.76; P = 2.62 × 10-8) and in the male-only GWAS (lead variant rs2968545: (Beta = -6.50; P = 1.09 × 10-9), and one suggestive variant was found at 13q12.11 in the female-only GWAS (rs79926925: Beta = 6.95; P = 8.15 × 10-8). The negatively associated variants were most common in European Americans (T allele of rs79837492; 5%) and African Americans (C allele of rs2968545; 5%) and not observed in Japanese Americans, whereas the positively associated variant was most common in Japanese Americans (C allele of rs79926925, 5%), which was all consistent with the racial/ethnic %VAT differences. In a validation step among UK Biobank participants (N = 23,699 of mainly British and Irish ancestry) with MRI-based VAT volume, both rs79837492 (Beta = -0.026, P = 0.019) and rs2968545 (Beta = -0.028, P = 0.010) were significantly associated in men only (n = 11,524). In the MEC-APS, the association between rs79926925 and plasma sex hormone binding globulin levels reached statistical significance in females, but not in males, with adjustment for total adiposity (Beta = -0.24; P = 0.028), on the log scale. Rs79837492 and rs2968545 are located in intron 5 of CNTNAP5, and rs79926925, in an intergenic region between GJB6 and CRYL1. These novel findings differing by sex and racial/ethnic group warrant replication in additional diverse studies with direct visceral fat measurements., Competing Interests: The authors have declared that no competing interests exit., (Copyright: © 2023 Streicher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify the acrolein-DNA adduct (8 R / S )-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2- a ]purine-10(3 H )-one (γ-OH-Acr-dGuo, 1 ) and the lipid peroxidation-related DNA adduct 1, N 6 -etheno-dAdo (εdAdo, 2 ) in DNA obtained by oral rinse from 101 Native Hawaiians, 101 Whites, and 79 Japanese Americans. Levels of urinary biomarkers of nicotine, acrolein, acrylonitrile, and a mixture of crotonaldehyde, methyl vinyl ketone, and methacrolein were also quantified. Whites had significantly higher levels of γ-OH-Acr-dGuo than Japanese Americans and Native Hawaiians after adjusting for age and sex. There was no significant difference in levels of this DNA adduct between Japanese Americans and Native Hawaiians, which is not consistent with the high lung cancer risk of Native Hawaiians. Levels of εdAdo were modestly higher in Whites and Native Hawaiians than in Japanese Americans. The lower level of DNA adducts in the oral cells of Japanese American cigarette smokers than Whites is consistent with their lower risk for lung cancer. The higher levels of εdAdo, but not γ-OH-Acr-dGuo, in Native Hawaiian versus Japanese American cigarette smokers suggest that lipid peroxidation and related processes may be involved in their high risk for lung cancer, but further studies are required.

Rationale: Although the contribution of air pollution to lung cancer risk is well characterized, few studies have been conducted in racially, ethnically, and socioeconomically diverse populations. Objectives: To examine the association between traffic-related air pollution and risk of lung cancer in a racially, ethnically, and socioeconomically diverse cohort. Methods: Among 97,288 California participants of the Multiethnic Cohort Study, we used Cox proportional hazards regression to examine associations between time-varying traffic-related air pollutants (gaseous and particulate matter pollutants and regional benzene) and lung cancer risk ( n  = 2,796 cases; average follow-up = 17 yr), adjusting for demographics, lifetime smoking, occupation, neighborhood socioeconomic status (nSES), and lifestyle factors. Subgroup analyses were conducted for race, ethnicity, nSES, and other factors. Measurements and Main Results: Among all participants, lung cancer risk was positively associated with nitrogen oxide (hazard ratio [HR], 1.15 per 50 ppb; 95% confidence interval [CI], 0.99-1.33), nitrogen dioxide (HR, 1.12 per 20 ppb; 95% CI, 0.95-1.32), fine particulate matter with aerodynamic diameter <2.5 μm (HR, 1.20 per 10 μg/m 3 ; 95% CI, 1.01-1.43), carbon monoxide (HR, 1.29 per 1,000 ppb; 95% CI, 0.99-1.67), and regional benzene (HR, 1.17 per 1 ppb; 95% CI, 1.02-1.34) exposures. These patterns of associations were driven by associations among African American and Latino American groups. There was no formal evidence for heterogeneity of effects by nSES ( P heterogeneity > 0.21), although participants residing in low-SES neighborhoods had increased lung cancer risk associated with nitrogen oxides, and no association was observed among those in high-SES neighborhoods. Conclusions: These findings in a large multiethnic population reflect an association between lung cancer and the mixture of traffic-related air pollution and not a particular individual pollutant. They are consistent with the adverse effects of air pollution that have been described in less racially, ethnically, and socioeconomically diverse populations. Our results also suggest an increased risk of lung cancer among those residing in low-SES neighborhoods.

One mechanism by which genetic factors influence complex traits and diseases is altering gene expression. Direct measurement of gene expression in relevant tissues is rarely tenable; however, genetically regulated gene expression (GReX) can be estimated using prediction models derived from large multi-omic datasets. These approaches have led to the discovery of many gene-trait associations, but whether models derived from predominantly European ancestry (EA) reference panels can map novel associations in ancestrally diverse populations remains unclear. We applied PrediXcan to impute GReX in 51,520 ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) participants (35% African American, 45% Hispanic/Latino, 10% Asian, and 7% Hawaiian) across 25 key cardiometabolic traits and relevant tissues to identify 102 novel associations. We then compared associations in PAGE to those in a random subset of 50,000 White British participants from UK Biobank (UKBB 50k ) for height and body mass index (BMI). We identified 517 associations across 47 tissues in PAGE but not UKBB 50k , demonstrating the importance of diverse samples in identifying trait-associated GReX. We observed that variants used in PrediXcan models were either more or less differentiated across continental-level populations than matched-control variants depending on the specific population reflecting sampling bias. Additionally, variants from identified genes specific to either PAGE or UKBB 50k analyses were more ancestrally differentiated than those in genes detected in both analyses, underlining the value of population-specific discoveries. This suggests that while EA-derived transcriptome imputation models can identify new associations in non-EA populations, models derived from closely matched reference panels may yield further insights. Our findings call for more diversity in reference datasets of tissue-specific gene expression., Competing Interests: Declaration of interests E.E.K. has received speaker honoraria from Illumina, 23andMe, and Regeneron Pharmaceuticals and serves as a scientific board member for Galateo Bio., (Copyright © 2022 American Society of Human Genetics. All rights reserved.)

Background: Age-related loss in skeletal muscle mass, quality, and strength, known as sarcopenia, is a well-known phenomenon of aging and is determined clinically using methods such as dual-energy X-ray absorptiometry (DXA). However, these clinical methods to measure sarcopenia are not practical for population-based studies, and a five-question screening tool known as SARC-F has been validated to screen for sarcopenia., Methods: We investigated the relationship between appendicular skeletal lean mass/height 2 (ALM/HT 2 ) (kg/m 2 ) assessed by DXA and SARC-F in a subset of 1538 (778 men and 760 women) participants in the Multiethnic Cohort (MEC) Study after adjustment for race/ethnicity, age, and body mass index (BMI) at the time of DXA measurement. We then investigated the association between SARC-F and mortality among 71 283 (41 757 women and 29 526 men) participants in the MEC, who responded to the five SARC-F questions on a mailed questionnaire as part of the MEC follow-up in 2012-2016., Results: In women, SARC-F score was significantly inversely associated with ALM/HT 2 after adjusting for race/ethnicity, and age and BMI at DXA (r = -0.167, P < 0.001); the result was similar in men although it did not reach statistical significance (r = -0.056, P = 0.12). Among the 71 000+ MEC participants, SARC-F score ≥ 4, as an indicator of sarcopenia, was higher in women (20.9%) than in men (11.2%) (P < 0.0001) and increased steadily with increasing age (6.3% in <70 vs. 41.3% in 90+ years old) (P < 0.0001). SARC-F score ≥ 4 was highest among Latinos (30.8% in women and 16.1% in men) and lowest in Native Hawaiian women (15.6%) and Japanese American men (8.9%). During an average of 6.8 years of follow-up, compared with men with SARC-F score of 0-1 (indicator of no sarcopenia), men with SARC-F 2-3 (indicator of pre-sarcopenia) and SARC-F ≥ 4 had significantly increased risk of all-cause mortality [hazard ratio (HR) = 1.00, 1.77, 3.73, P < 0.001], cardiovascular disease (CVD) mortality (HR = 1.00, 1.85, 3.98, P < 0.001), and cancer mortality (HR = 1.00, 1.46, 1.96, P < 0.001) after covariate adjustment. Comparable risk association patterns with SARC-F scores were observed in women (all-cause mortality: HR = 1.00, 1.47, 3.10, P < 0.001; CVD mortality: HR = 1.00, 1.59, 3.54, P < 0.001; cancer mortality: HR = 1.00, 1.30, 1.77, P < 0.001). These significant risk patterns between SARC-F and all-cause mortality were found across all sex-race/ethnic groups considered (12 in total)., Conclusions: An indicator of sarcopenia, determined using SARC-F, showed internal validity against DXA and displayed racial/ethnic and sex differences in distribution. SARC-F was associated with all-cause mortality as well as cause-specific mortality., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Within the Multiethnic Cohort (MEC), we examined the association between air pollution and mortality among African American, European American, Japanese American, and Latina American women diagnosed with breast cancer., Methods: We used a land use regression (LUR) model and kriging interpolation to estimate nitrogen oxides (NO x , NO 2 ) and particulate matter (PM 2.5 , PM 10 ) exposures for 3,089 breast cancer cases in the MEC, who were diagnosed from 1993 through 2013 and resided largely in Los Angeles County, California. Cox proportional hazards models were used to examine the association of time-varying air pollutants with all-cause, breast cancer, cardiovascular disease (CVD), and non-breast cancer/non-CVD mortality, accounting for key covariates., Results: We identified 1,125 deaths from all causes (474 breast cancer, 272 CVD, 379 non-breast cancer/non-CVD deaths) among the 3,089 breast cancer cases with 8.1 years of average follow-up. LUR and kriged NO X (per 50 ppb) and NO 2 (per 20 ppb), PM 2.5 (per 10 µg/m 3 ), and PM 10 (per 10 µg/m 3 ) were positively associated with risks of all-cause (Hazard Ratio (HR) range = 1.13-1.25), breast cancer (HR range = 1.19-1.45), and CVD mortality (HR range = 1.37-1.60). Associations were statistically significant for LUR NO X and CVD mortality (HR = 1.60; 95% CI: 1.08-2.37) and kriged NO 2 and breast cancer mortality (HR = 1.45; 95% CI 1.02-2.07). Gaseous and PM pollutants were positively associated with breast cancer mortality across racial/ethnic group., Conclusion: In this study, air pollutants have a harmful impact on breast cancer survival. Additional studies should evaluate potential confounding by socioeconomic factors. These data support maintaining clean air laws to improve survival for women with breast cancer., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Scientific Committee 6-9 was established by the National Council on Radiation Protection and Measurements (NCRP), charged to provide guidance in the derivation of organ doses and their uncertainty, and produced a report, NCRP Report No. 178, Deriving Organ Doses and their Uncertainty for Epidemiologic Studies with a focus on the Million Person Study of Low-Dose Radiation Health Effects (MPS). This review summarizes the conclusions and recommendations of NCRP Report No. 178, with a concentration on and overview of the dosimetry and uncertainty approaches for the cohorts in the MPS, along with guidelines regarding the essential approaches used to estimate organ doses and their uncertainties (from external and internal sources) within the framework of an epidemiologic study., Conclusions: The success of the MPS is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. The dosimetry aspects for the MPS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. Specific dosimetric reconstruction issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma- or x-ray sources, for some of the study groups, there is also a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments.