Prospective analysis of sleep characteristics, chronotype, and risk of breast cancer in the california teachers study.

PURPOSE: Poor sleep quality and evening chronotype were associated with increased risk of breast cancer in a previous retrospective study in the California Teachers Study (CTS). The present analysis examines these sleep factors prospectively in the same cohort of women. METHODS: From the CTS, we included 1,085 incident breast cancer cases and 38,470 cancer-free participants from 2012 through 2019. We calculated time at risk and used Cox proportional hazards regression models to estimate the hazard ratios (HRs) and control for risk factors such as age, race, body mass index, family history of breast cancer, and reproductive history. The sleep factors examined were quality, latency, duration, disturbance, and sleep medication use, based on a shortened version of the Pittsburgh Sleep Quality Index, as well as chronotype (preference for morning or evening activity). This analysis was limited to women who were post-menopausal at the time they answered these sleep-related questions. RESULTS: Measures of sleep quality did not appear to be associated with subsequent breast cancer risk. The HR for evening chronotypes compared to morning chronotypes was somewhat elevated (HR 1.19, 95% CI 1.04, 1.36). CONCLUSION: While the measures of sleep quality and duration were not associated with post-menopausal breast cancer risk in this prospective analysis, the modestly elevated risk observed for evening chronotypes was consistent with the prior retrospective analysis.

Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnoses.

BACKGROUND: Some hormonally active cancers have low survival rates, but a large proportion of their incidence remains unexplained. Endocrine disrupting chemicals may affect hormone pathways in the pathology of these cancers. OBJECTIVE: To evaluate cross-sectional associations between per- and polyfluoroalkyl substances (PFAS), phenols, and parabens and self-reported previous cancer diagnoses in the National Health and Nutrition Examination Survey (NHANES). METHODS: We extracted concentrations of 7 PFAS and 12 phenols/parabens and self-reported diagnoses of melanoma and cancers of the thyroid, breast, ovary, uterus, and prostate in men and women (≥20 years). Associations between previous cancer diagnoses and an interquartile range increase in exposure biomarkers were evaluated using logistic regression models adjusted for key covariates. We conceptualized race as social construct proxy of structural social factors and examined associations in non-Hispanic Black, Mexican American, and other Hispanic participants separately compared to White participants. RESULTS: Previous melanoma in women was associated with higher PFDE (OR:2.07, 95% CI: 1.25, 3.43), PFNA (OR:1.72, 95% CI: 1.09, 2.73), PFUA (OR:1.76, 95% CI: 1.07, 2.89), BP3 (OR: 1.81, 95% CI: 1.10, 2.96), DCP25 (OR: 2.41, 95% CI: 1.22, 4.76), and DCP24 (OR: 1.85, 95% CI: 1.05, 3.26). Previous ovarian cancer was associated with higher DCP25 (OR: 2.80, 95% CI: 1.08, 7.27), BPA (OR: 1.93, 95% CI: 1.11, 3.35) and BP3 (OR: 1.76, 95% CI: 1.00, 3.09). Previous uterine cancer was associated with increased PFNA (OR: 1.55, 95% CI: 1.03, 2.34), while higher ethyl paraben was inversely associated (OR: 0.31, 95% CI: 0.12, 0.85). Various PFAS were associated with previous ovarian and uterine cancers in White women, while MPAH or BPF was associated with previous breast cancer among non-White women. IMPACT STATEMENT: Biomarkers across all exposure categories (phenols, parabens, and per- and poly- fluoroalkyl substances) were cross-sectionally associated with increased odds of previous melanoma diagnoses in women, and increased odds of previous ovarian cancer was associated with several phenols and parabens. Some associations differed by racial group, which is particularly impactful given the established racial disparities in distributions of exposure to these chemicals. This is the first epidemiological study to investigate exposure to phenols in relation to previous cancer diagnoses, and the first NHANES study to explore racial/ethnic disparities in associations between environmental phenol, paraben, and PFAS exposures and historical cancer diagnosis.

Probabilistic risk assessment of residential exposure to metal(loid)s in a mining impacted community.

The "Gold Country" region of California is impacted by legacy and active gold mines. Concomitantly, Gold Country has an increased rate of female breast cancer relative to the state average. Using community-based participatory research methods, 40 participants completed surveys and collected a total of 354 water, soil, home-grown foods, and dust samples from their homes, which we compared to state, federal, and international contamination standards for arsenic, cadmium, and lead. All soil samples exceeded U.S. EPA and California EPA soil standards for arsenic. When comparing other media to state, federal and international standards for arsenic, cadmium, and lead, 15 additional exceedances for indoor/outdoor dust, drinking water, and/or vegetable were documented. A probabilistic risk assessment was conducted to determine an adult female's exposure to arsenic, cadmium, and lead and estimated risk. Arsenic exposure, due largely to water (63.5 %) and homegrown food (33.3 %), presents carcinogenic risks in excess of the EPA recommended upper limit for contaminated sites (1 × 10-4) in 12.5 % of scenarios, and exceeds a risk level of 1 × 10-6 in 98.0 % of cases. Cadmium exposure results mainly from homegrown food consumption (83.7 %), and lead exposure results from a broader range of sources. This research indicates that rural areas in Gold Country face environmental exposures different than in urban areas. Exposure to arsenic in the female population of Gold Country may be driven by consumption of home-grown foods and water, and exposure to cadmium is driven by home-grown food intake. Since mining sites are of concern internationally, this risk assessment process and associated findings are significant and can be used to inform and tailor public health interventions. The weight of the evidence suggests that the arsenic exposure identified in this study could contribute to increases in the cancer rate among those living in Gold Country, California.

Risk prediction models for endometrial cancer: development and validation in an international consortium.

BACKGROUND: Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. METHODS: We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses' Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. RESULTS: Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O] = 1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O = 1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O = 0.55, 95% CI = 0.51 to 0.59). CONCLUSIONS: Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.

Differential newborn DNA methylation among individuals with complex congenital heart defects and childhood lymphoma.

BACKGROUND: There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on "CHD-lymphoma" associations. METHODS: From >3 million live births (1988-2004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD-lymphoma through the California BioBank. We performed case-control epigenome-wide association analyses (EWAS) using two comparison groups with reciprocal discovery and validation to identify differential methylation associated with CHD-lymphoma. RESULTS: After correction for multiple testing at the discovery and validation stages, individuals with CHD-lymphoma had differential newborn methylation at six sites relative to two comparison groups. Our top finding was significant in both EWAS and indicates PPFIA1 cg25574765 was hypomethylated among individuals with CHD-lymphoma (mean beta = 0.04) relative to both unaffected individuals (mean beta = 0.93, p = 1.5 × 10-12 ) and individuals with complex CHD (mean beta = 0.95, p = 3.8 × 10-8 ). PPFIA1 encodes a ubiquitously expressed liprin protein in one of the most commonly amplified regions in many cancers (11q13). Further, cg25574765 is a proposed marker of pre-eclampsia, a maternal CHD risk factor that has not been fully evaluated for lymphoma risk in offspring, and the tumor microenvironment that may drive immune cell malignancies. CONCLUSIONS: We identified associations between molecular changes present in the genome at birth and risk of childhood lymphoma among those with CHD. Our findings also highlight novel perinatal exposures that may underlie methylation changes in CHD predisposing to lymphoma.

Association between long-term exposure to particulate air pollution with SARS-CoV-2 infections and COVID-19 deaths in California, U.S.A.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 µm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.

Coffee consumption and risk of endometrial cancer: a pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: Epidemiologic studies suggest that coffee consumption may be inversely associated with risk of endometrial cancer (EC), the most common gynecological malignancy in developed countries. Furthermore, coffee consumption may lower circulating concentrations of estrogen and insulin, hormones implicated in endometrial carcinogenesis. Antioxidants and other chemopreventive compounds in coffee may have anticarcinogenic effects. Based on available meta-analyses, the World Cancer Research Fund (WCRF) concluded that consumption of coffee probably protects against EC. OBJECTIVES: Our main aim was to examine the association between coffee consumption and EC risk by combining individual-level data in a pooled analysis. We also sought to evaluate potential effect modification by other risk factors for EC. METHODS: We combined individual-level data from 19 epidemiologic studies (6 cohort, 13 case-control) of 12,159 EC cases and 27,479 controls from the Epidemiology of Endometrial Cancer Consortium (E2C2). Logistic regression was used to calculate ORs and their corresponding 95% CIs. All models were adjusted for potential confounders including age, race, BMI, smoking status, diabetes status, study design, and study site. RESULTS: Coffee drinkers had a lower risk of EC than non-coffee drinkers (multiadjusted OR: 0.87; 95% CI: 0.79, 0.95). There was a dose-response relation between higher coffee consumption and lower risk of EC: compared with non-coffee drinkers, the adjusted pooled ORs for those who drank 1, 2-3, and >4 cups/d were 0.90 (95% CI: 0.82, 1.00), 0.86 (95% CI: 0.78, 0.95), and 0.76 (95% CI: 0.66, 0.87), respectively (P-trend < 0.001). The inverse association between coffee consumption and EC risk was stronger in participants with BMI > 25 kg/m2. CONCLUSIONS: The results of the largest analysis to date pooling individual-level data further support the potentially beneficial health effects of coffee consumption in relation to EC, especially among females with higher BMI.

Returning Individual Tap Water Testing Results to Research Study Participants after a Wildfire Disaster.

After the devastating wildfire that destroyed most of the town of Paradise, California in 2018, volatile organic compounds were found in water distribution pipes. Approximately 11 months after the fire, we collected tap water samples from 136 homes that were still standing and tested for over 100 chemicals. Each participant received a customized report showing the laboratory findings from their sample. Our goal was to communicate individual water results and chemical information rapidly in a way that was understandable, scientifically accurate, and useful to participants. On the basis of this process, we developed a framework to illustrate considerations and priorities that draw from best practices of previous environmental results return research and crisis communication, while also addressing challenges specific to the disaster context. We also conducted a follow-up survey on participants' perceptions of the results return process. In general, participants found the results return communications to be understandable, and they felt less worried about their drinking water quality after receiving the information. Over one-third of the participants reported taking some kind of action around their water usage habits after receiving their results. Communication with participants is a critical element of environmental disaster research, and it is important to have a strategy to communicate results that achieves the goals of timeliness, clarity, and scientific accuracy, ultimately empowering people toward actions that can reduce exposure.

Host characteristics associated with serologic inflammatory biomarkers in women.

BACKGROUND: There is growing evidence that exposure to low-grade inflammation may be associated with adverse health outcomes. METHODS: We conducted a cross-sectional study within the California Teachers Study prospective cohort, among female participants who had completed a questionnaire that asked about their health behaviors (e.g., diabetes, physical activity, body mass index, medication use) and who had donated blood within a year of their questionnaire. 822 women with stored serum were evaluated for 16 immune biomarkers. In addition, four immune pathways were constructed: Th1, pro-inflammatory/macrophage activation, B-cell activation, and T-cell activation. Odds ratios (ORs) and 95% confidence intervals (CI) for the association between host characteristics and immune biomarkers were assessed using logistic regression models. RESULT: Compared to women of a normal BMI, obese women (>30 kg/m2) were positively associated with sTNFR2, CD27, IL6, CXCL13, sIL-2Rα, and IL6Ra levels above the median, with odds ratios ranging from 1.5 to 6.0. The pro-inflammatory/macrophage activation pathway was positively associated with diabetes (OR = 2.12, 95% CI = 1.14-3.95), fueled by individual associations between diabetes and sTNF-R2, TNFα and sCD27. Physical activity was inversely associated with sTNF-R2, TNFα, CXCL13, IL6, IL10, and IFN-γ levels, particularly for the highest category of activity (5.88+ hours/week) (ORs = 0.32-0.69). In pathway-based analyses, the Th1 pathway which includes decreased levels of IL4 and IL10 was positively associated with elevated physical activity (OR = 1.5). In contrast, the pro-inflammatory, B- and T-cell activation pathways were positively associated with higher BMI (OR ranging from 1.6 to 3) and inversely associated with increasing levels of physical activity. CONCLUSIONS: Several host characteristics were associated with circulating levels of immune biomarkers, including markers of inflammation. Further understanding of associations between immune marker profiles with human disease are warranted.

Development of a Data Visualization Tool for Occupational Exposure to Chemicals of Concern for Breast Cancer Among California Working Women, 2010-2014.

We identified the occupations that employ California women and a list of chemicals of concern for breast cancer. We evaluated the likelihood of on-the-job exposure to the categories of chemicals by occupation among formally and informally employed women. We selected 145 occupations representing more than 6.6 million women (85% of California working women), along with an additional sixteen occupations for informal workers only. We organized 1012 chemicals (including mammary gland carcinogens, developmental toxicants, and endocrine-disrupting chemicals) into twenty-five categories. More than 80 percent of occupations investigated had possible or probable exposure to at least one category of chemicals. This is the first categorization of occupational exposure to chemicals of concern for breast cancer among California working women. Our investigation revealed significant data gaps, which could be improved by policy changes resulting in enhanced collection of data on occupation and chemical exposure.

Incidence of Lung Cancer Among Never-Smoking Asian American, Native Hawaiian, and Pacific Islander Females.

BACKGROUND: Although lung cancer incidence rates according to smoking status, sex, and detailed race/ethnicity have not been available, it is estimated that more than half of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. METHODS: We calculated age-adjusted incidence rates for lung cancer according to smoking status and detailed race/ethnicity among females, focusing on AANHPI ethnic groups, and assessed relative incidence across racial/ethnic groups. We used a large-scale dataset that integrates data from electronic health records from 2 large health-care systems-Sutter Health in Northern California and Kaiser Permanente Hawai'i-linked to state cancer registries for incident lung cancer diagnoses between 2000 and 2013. The study population included 1 222 694 females (n = 244 147 AANHPI), 3297 of which were diagnosed with lung cancer (n = 535 AANHPI). RESULTS: Incidence of lung cancer among never-smoking AANHPI as an aggregate group was 17.1 per 100 000 (95% confidence interval [CI] = 14.9 to 19.4) but varied widely across ethnic groups. Never-smoking Chinese American females had the highest rate (22.8 per 100 000, 95% CI = 17.3 to 29.1). Except for Japanese American females, incidence among every never-smoking AANHPI female ethnic group was higher than that of never-smoking non-Hispanic White females, from 66% greater among Native Hawaiian females (incidence rate ratio = 1.66, 95% CI = 1.03 to 2.56) to more than 100% greater among Chinese American females (incidence rate ratio = 2.26, 95% CI = 1.67 to 3.02). CONCLUSIONS: Our study revealed high rates of lung cancer among most never-smoking AANHPI female ethnic groups. Our approach illustrates the use of innovative data integration to dispel the myth that AANHPI females are at overall reduced risk of lung cancer and demonstrates the need to disaggregate this highly diverse population.

Methylation biomarkers of polybrominated diphenyl ethers (PBDEs) and association with breast cancer risk at the time of menopause.

BACKGROUND: Exposure to polybrominated diphenyl ethers (PBDEs) may influence risk of developing post-menopausal breast cancer. Although mechanisms are poorly understood, epigenetic regulation of gene expression may play a role. OBJECTIVES: To identify DNA methylation (DNAm) changes associated with PBDE serum levels and test the association of these biomarkers with breast cancer risk. METHODS: We studied 397 healthy women (controls) and 133 women diagnosed with breast cancer (cases) between ages 40 and 58 years who participated in the California Teachers Study. PBDE levels were measured in blood. Infinium Human Methylation EPIC Bead Chips were used to measure DNAm. Using multivariable linear regression models, differentially methylated CpG sites (DMSs) and regions (DMRs) associated with serum PBDE levels were identified using controls. For top-ranked DMSs and DMRs, targeted next-generation bisulfite sequencing was used to measure DNAm for 133 invasive breast cancer cases and 301 age-matched controls. Conditional logistic regression was used to evaluate associations between DMSs and DMRs and breast cancer risk. RESULTS: We identified 15 DMSs and 10 DMRs statistically significantly associated with PBDE levels (FDR < 0.05). Methylation changes in a DMS at BMP8B and DMRs at TP53 and A2M-AS1 were statistically significantly (FDR < 0.05) associated with breast cancer risk. CONCLUSION: We show for the first time that serum PBDE levels are associated with differential methylation and that PBDE-associated DNAm changes in blood are associated with breast cancer risk.

Fire and Water: Assessing Drinking Water Contamination After a Major Wildfire.

We investigated patterns of volatile organic compound (VOC) contamination in drinking water systems affected by the California 2018 Camp Fire. We performed spatial analysis of over 5000 water samples collected over a 17 month period by a local water utility, sampled tap water for VOCs in approximately 10% (N = 136) of standing homes, and conducted additional nontargeted chemical analysis of 10 samples. Benzene contamination was present in 29% of service connections to destroyed structures and 2% of service connections to standing homes. A spatial pattern was apparent. Tap water in standing homes 11 months after the fire contained low concentrations of benzene in 1% of samples, but methylene chloride was present in 19% of samples, including several above regulatory limits. Elevated methylene chloride was associated with greater distance from the water meter to the tap, longer stagnation time, and the presence of a destroyed structure on the service connection; it was inversely associated with certain trihalomethanes. Nontargeted analysis identified multiple combustion byproducts in the water at 2/10 homes. Our findings support the hypothesis that pyrolysis and smoke intrusion from depressurization contributed to the benzene contamination. Further research is needed to test the hypothesis that methylene chloride may be generated from the dehalogenation of disinfection byproducts stagnating in galvanized iron pipes.

Sex differences in associations between birth characteristics and childhood cancers: a five-state registry-linkage study.

BACKGROUND: There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. METHODS: Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction < 0.01) by sex was evaluated for each characteristic in each cancer. RESULTS: Males comprised > 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction < 0.01) including gestational age for ALL (female, 40 vs. 37-39 weeks OR: 0.84, 95% CI 0.73-0.97) and ependymoma (female, 40 vs. 37-39 OR: 1.78, 95% CI 1.14-2.79; female, ≥ 41 OR: 2.01. 95% CI 1.29-3.14), birth order for AML (female, ≥ 3rd vs. 1st OR: 1.39, 95% CI 1.01-1.92), maternal education for Hodgkin lymphoma (male, any college vs. < high school[HS] OR: 1.47, 95% CI 1.03-2.09) and Wilms tumor (female, any college vs. HS OR: 0.74, 95% CI 0.59-0.93), maternal race/ethnicity for neuroblastoma (male, black vs. white OR: 2.21, 95% CI 1.21-4.03; male, Hispanic vs. white OR: 1.86, 95% CI 1.26-2.75; female, Asian/Pacific Islander vs. white OR: 0.28, 95% CI 0.12-0.69), and paternal age (years) for hepatoblastoma in males (< 24 vs. 25-29 OR: 2.17, 95% CI 1.13-4.19; ≥ 35 vs. 25-29 OR: 2.44, 95% CI 1.28-4.64). CONCLUSIONS: These findings suggest etiologic heterogeneity by sex for childhood cancers for gestational age, maternal education, and race/ethnicity and paternal age.

Residential exposure to carbamate, organophosphate, and pyrethroid insecticides in house dust and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Self-reported residential use of pesticides has consistently been associated with increased risk of childhood leukemia. However, these studies were limited in their ability to identify specific insecticide active ingredients that were associated with risk. OBJECTIVE: We used household carpet dust measurements of 20 insecticides (two carbamate, 10 organophosphate, two organochlorine, and six pyrethroid) as indicators of exposure and evaluated associations with the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: We conducted a population-based case-control study of 252 ALL cases diagnosed from 1999 to 2007 and 306 birth certificate controls from 35 counties in Central and Northern California. Carpet dust was collected at a second interview (2001-2007) for cases who had not moved since diagnosis (comparable reference date for controls) using a specialized vacuum cleaner in the room where the child spent most of their time or from the household vacuum. Insecticides were categorized as detected (yes/no), or as tertiles or quartiles of their distributions among controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for demographic characteristics, interview year, and season of dust collection. RESULTS: Permethrin, chlorpyrifos, diazinon, and carbaryl were the most frequently detected insecticide active ingredients. When we compared the highest quartile to the lowest or to non-detections, there was no association with ALL for permethrin (OR Q4 vs. Q1 = 0.81; 95% CI 0.50-1.31), carbaryl (OR Q4 vs. non-detects = 0.61, 95% CI 0.34-1.08) or chlorpyrifos (OR Q4 vs. Q1 = 0.60; 95% CI 0.36-1.00). The highest quartile of diazinon concentration was inversely associated with risk in the single pesticide model but without a monotonic exposure-response (p-trend = 0.14). After adjusting for other common insecticides, the OR was not significant (OR Q4 vs. Q1 = 0.58; 95% CI 0.33-1.05). None of the other insecticides were associated with risk. CONCLUSION: Our results should be interpreted within the limitations of the case-control study design including the use of a single post-diagnosis dust sample and restriction to residentially stable participants, which may have resulted in selection bias. Although difficult to implement, additional studies with assessment of exposure to insecticide active and non-active ingredients are necessary to elucidate the role of these common exposures in childhood leukemia risk.

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.

Integrating Electronic Health Record, Cancer Registry, and Geospatial Data to Study Lung Cancer in Asian American, Native Hawaiian, and Pacific Islander Ethnic Groups.

BACKGROUND: A relatively high proportion of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. We used an integrative data approach to assemble a large-scale cohort to study lung cancer risk among AANHPIs by smoking status with attention to representation of specific AANHPI ethnic groups. METHODS: We leveraged electronic health records (EHRs) from two healthcare systems-Sutter Health in northern California and Kaiser Permanente Hawai'i-that have high representation of AANHPI populations. We linked EHR data on lung cancer risk factors (i.e., smoking, lung diseases, infections, reproductive factors, and body size) to data on incident lung cancer diagnoses from statewide population-based cancer registries of California and Hawai'i for the period between 2000 and 2013. Geocoded address data were linked to data on neighborhood contextual factors and regional air pollutants. RESULTS: The dataset comprises over 2.2 million adult females and males of any race/ethnicity. Over 250,000 are AANHPI females (19.6% of the female study population). Smoking status is available for over 95% of individuals. The dataset includes 7,274 lung cancer cases, including 613 cases among AANHPI females. Prevalence of never-smoking status varied greatly among AANHPI females with incident lung cancer, from 85.7% among Asian Indian to 14.4% among Native Hawaiian females. CONCLUSION: We have developed a large, multilevel dataset particularly well-suited to conduct prospective studies of lung cancer risk among AANHPI females who never smoked. IMPACT: The integrative data approach is an effective way to conduct cancer research assessing multilevel factors on cancer outcomes among small populations.

Chronotype and risk of post-menopausal endometrial cancer in the California Teachers Study.

Working at night causes circadian disruption and it has been classified as a probable carcinogen. An evening chronotype, or preference for late day activity, has been shown to increase risk for several adverse health effects, such as metabolic disorders and recently, breast cancer. To further explore this emerging area of interest, we examined the association between endometrial cancer (EC) risk, another common cancer in women, and chronotype. The women in this study were members of the California Teachers Study cohort, which was established in 1995. Chronotype was reported on a subsequent questionnaire (Q5), administered in 2012-2013. The women included in this analysis were under age 90 years, were post-menopausal at Q5, and had no hysterectomy. The cancer cases, identified through linkages to the California Cancer Registry, were diagnosed between 1996 and 2014. We used unconditional logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between chronotype and EC diagnosis. There were 437 EC cases and 26,753 cancer-free controls included in this analysis. Controls were more likely to classify themselves as current morning chronotypes than were cases (39% and 34%, respectively). Compared to morning types, women who were definite evening types had a statistically significantly elevated OR of 1.44 (95% CI 1.09-1.91). This association was more pronounced among obese women as compared to non-obese women. For evening type compared to morning type, the OR among obese women was 2.01 (95% CI 1.23, 3.29) while the OR for non-obese women was 1.12 (95% CI 0.77, 1.63). To our knowledge, the association between EC risk and evening chronotype has not been previously reported, but is consistent with the small body of literature which suggests increased breast cancer risks among evening chronotypes. Because this study was based on a retrospective analysis in a cohort of mostly white female teachers in California, further analysis of chronotype as a potential EC risk factor should be considered in other cohorts and in prospective analyses in order to further explore this relationship.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Urinary cadmium and timing of menarche and pubertal development in girls.

BACKGROUND: Cadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty. OBJECTIVES: To determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development. METHODS: A cohort of 211 girls, ages 10-13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth. RESULTS: The baseline geometric mean creatinine-adjusted Cd concentration was 0.22 µg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 µg/L were less likely to have attained menarche than girls with urinary Cd < 0.2 µg/L (hazard ratio = 0.42; 95% confidence interval, 0.23-0.78). Urinary Cd was negatively associated with pubic hair growth (p-trend = 0.01) but not with breast development (p-trend = 0.72) at baseline. CONCLUSIONS: These findings suggest that a higher Cd body burden may delay some aspects of pubertal development among girls.