California Teachers Study Cohort Research Articles

Long-Term Exposure to Arsenic in Community Water Supplies and Risk of Cardiovascular Disease among Women in the California Teachers Study.

Inorganic arsenic in drinking water (wAs) is linked to atherosclerosis and cardiovascular disease. However, risk is uncertain at lower levels present in US community water supplies (CWS), currently regulated at the federal maximum contaminant level of . We evaluated the relationship between long-term wAs exposure from CWS and cardiovascular disease in the California Teachers Study cohort. Using statewide health care administrative records from enrollment through follow-up (1995-2018), we identified fatal and nonfatal cases of ischemic heart disease (IHD) and cardiovascular disease (CVD). Participants' residential addresses were linked to a network of CWS boundaries and annual wAs concentrations (1990-2020). Most participants resided in areas served by a CWS (92%). Exposure was calculated as a time-varying, 10-year moving average up to a participant's event, death, or end of follow-up. Using Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of IHD or CVD. We evaluated wAs exposure categorized by concentration thresholds relevant to regulation standards (, 1.00-2.99, 3.00-4.99, 5.00-9.99, ) and continuously using a log2-transformation (i.e., per doubling). Models were adjusted for baseline age, neighborhood socioeconomic status, race/ethnicity, body mass index (BMI), and smoking status. We also stratified analyses by age, BMI, and smoking status. Our analysis included 98,250 participants, 6,119 IHD cases, and 9,936 CVD cases. The HRs for IHD at concentration thresholds (reference, ) were 1.06 (95% CI: 1.00, 1.12), 1.05 (95% CI: 0.94, 1.17), 1.20 (95% CI: 1.02, 1.41), and 1.42 (95% CI: 1.10, 1.84) for , , , and , respectively. HRs for every doubling of wAs exposure were 1.04 (95% CI: 1.02, 1.06) for IHD and 1.02 (95% CI: 1.01, 1.04) for CVD. We observed statistically stronger risk among those vs. years of age at enrollment ( and 0.012 for IHD and CVD, respectively). Long-term wAs exposure from CWS, at and below the regulatory limit, may increase cardiovascular disease risk, particularly IHD. https://doi.org/10.1289/EHP14410.

Regulated water contaminants in community water supplies in the California Teachers Study cohort

Regulated water contaminants in community water supplies in the California Teachers Study cohort

Exposures to drinking water contaminants below regulatory limits and incident ovarian cancer in the California Teachers Study cohort

Exposures to drinking water contaminants below regulatory limits and incident ovarian cancer in the California Teachers Study cohort

Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort.

Pollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied. We described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators. Participants' geocoded addresses at enrollment (1995-1996) were linked to CWS service area boundaries and monitoring data (N = 115,206, 92%); we computed average (1990-2015) concentrations of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE). We used generalized linear regression to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption at follow-up (2017-2019) were also described. Medians (interquartile ranges) of average concentrations of all contaminants were below regulatory limits: arsenic: 1.03 (0.54,1.71) µg/L, uranium: 3.48 (1.01,6.18) µg/L, GA: 2.21 (1.32,3.67) pCi/L, nitrate: 0.54 (0.20,1.97) mg/L, HAA5: 8.67 (2.98,14.70) µg/L, and TTHM: 12.86 (4.58,21.95) µg/L. Among those who lived within a CWS boundary and self-reported drinking water information (2017-2019), approximately 74% self-reported their water source as municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Spatially linked water source was largely consistent with self-reported source at follow-up (2017-2019). Relative to non-Hispanic white participants, average arsenic, uranium, GA, and nitrate concentrations were higher for Black, Hispanic and Native American participants. Relative to participants living in census block groups in the lowest socioeconomic status (SES) quartile, participants in higher SES quartiles had lower arsenic/uranium/GA/nitrate, and higher HAA5/TTHM. Non-metropolitan participants had higher arsenic/uranium/nitrate, and metropolitan participants had higher HAA5/TTHM. Though average water contaminant levels were mostly below regulatory limits in this large cohort of California women, we observed heterogeneity in exposures across sociodemographic subgroups and neighborhood characteristics. These data will be used to support future assessments of drinking water exposures and disease risk.

Dietary patterns and the risk of hematological malignancy in the California Teachers study cohort.

10545 Background: Many studies show a correlation between diet and the risk of developing cancer, but most of these studies pertain to solid tumors and data linking certain diets to hematologic malignancies is scarce. This study aims to elucidate the effect of dietary patterns on the risk of developing hematologic malignancy. This study aims to elucidate dietary patterns and correlation with the risk of developing a hematologic malignancy. Methods: Data from 106,029 women in the California Teachers Study (CTS) cohort was analyzed, 476 participants were diagnosed with lymphocytic, monocytic, or other leukemia, 895 with Hodgkin’s or non-Hodgkin’s lymphoma, and 227 with multiple myeloma between 1995-2020. Results: Five major dietary patterns were identified as: 1) plant-based diet, characterized by a high consumption of fruit and vegetables, 2) high-protein, high-fat diet characterized by a high consumption of animal proteins animal protein (e.g., meat and eggs) and added fats (e.g., butter and mayonnaise), 3) high-carbohydrate diet characterized by a high consumption of convenience foods, pasta, and bread, 4) ethnic diet characterized by a high consumption of legumes, soy-based foods, rick and dark-green leafy vegetables and 5) the salad and wine diet characterized by high consumption of salad and low-fat dressing, fish, wine, coffee and tea, using principal factors analysis (PCFA). Relative risk and confidence intervals were analyzed for each dietary pattern and their correlation to a diagnosis of a hematologic malignancy. Models were adjusted for race-ethnicity/birthplace, living/working half a mile from a chemical plan, living/working half a mile from a powerplant, cigarette use, family history of leukemia and/or lymphoma, BMI (kg/m2), daily caloric intake (kcal/day), socioeconomic status, and moderate physical activity (h/wk). Overall, the high-carbohydrate diet was shown to be protective against hematologic malignancy risk with the lowest RR in all quintiles, but lowest in the 5th quintile (RR: 0.73; 95% CI: 0.59, 0.99, p=0.004). A high-carbohydrate diet was also shown to be associated with a reduction in multiple myeloma risk specifically with the lowest RR in all quintiles, but lowest in the 5th quintile (RR: 0.79; 95% CI: 0.63, 0.98, p=0.03). The ethnic diet was associated with a higher risk of multiple myeloma with the highest RR in all quintiles but highest in the 2nd quintile (RR:1.21; 95% CI 1.06, 1.39, p=0.006). Conclusions: The finding that the high-carbohydrate diet is associated with a reduced risk of a hematologic malignancy warrants further research to characterize the degree of risk reduction, what specific foods, if any, in the category offer protective effects, and if it is a potential approach for prevention.

Construction of residential histories to estimate long-term environmental exposures in the California Teachers Study cohort.

Environmental epidemiologic studies using geospatial data often estimate exposure at a participant's residence upon enrollment, but mobility during the exposure period can lead to misclassification. We aimed to mitigate this issue by constructing residential histories for participants in the California Teachers Study through follow-up (1995-2018). Address records have been collected from the US Postal Service, LexisNexis, Experian, and California Cancer Registry. We identified records of the same address based on geo-coordinate distance (≤250 m) and street name similarity. We consolidated addresses, prioritizing those confirmed by participants during follow-up questionnaires, and estimating the duration lived at each address using dates associated with records (e.g., date-first-seen). During 23 years of follow-up, about half of participants moved (48%, including 14% out-of-state). We observed greater mobility among younger women, Hispanic/Latino women, and those in metropolitan and lower socioeconomic status areas. The cumulative proportion of in-state movers remaining eligible for analysis was 21%, 32%, and 41% at 5, 10, and 20 years post enrollment, respectively. Using self-reported information collected 10 years after enrollment, we correctly identified 94% of movers and 95% of non-movers as having moved or not moved from their enrollment address. This dataset provides a foundation for estimating long-term environmental exposures in diverse epidemiologic studies in this cohort. IMPACT: Our efforts in constructing residential histories for California Teachers Study participants through follow-up (1995-2018) benefit future environmental epidemiologic studies. Address availability during the exposure period can mitigate misclassification due to residential changes, especially when evaluating long-term exposures and chronic health outcomes. This can reduce differential misclassification among more mobile subgroups, including younger women and those from lower socioeconomic and urban areas. Our approach to consolidating addresses from multiple sources showed high accuracy in comparison to self-reported residential information. The residential dataset produced from this analysis provides a valuable tool for future studies, ultimately enhancing our understanding of environmental health impacts.

Environmental Influences on Sleep in the California Teachers Study Cohort.

Only two-thirds of Americans meet the recommended 7 hours of sleep nightly. Insufficient sleep and circadian disruption have been associated with adverse health outcomes, including diabetes and cardiovascular disease. Several environmental disruptors of sleep have been reported, such as artificial light at night (ALAN) and noise. These studies tended to evaluate exposures individually. We evaluated several spatially derived environmental exposures (ALAN, noise, green space, and air pollution) and self-reported sleep outcomes obtained in 2012–2015 in a large cohort of 51,562 women in the California Teachers Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for sleep duration and latency. After adjusting for age, race/ethnicity, chronotype, use of sleep medication, and self-reported trouble sleeping, ALAN (per 5 millicandela (mcd)/m2 luminance, OR = 1.13, 95% CI: 1.07, 1.20) and air pollution (per 5 μg/m3 PM2.5, OR = 1.06, 95% CI: 1.04, 1.09) were associated with shorter sleep duration (<7 hours), and noise was associated with longer latency (>15 minutes) (per 10 decibels, OR = 1.05, 95% CI: 1.01, 1.10). Green space was associated with increased duration (per 0.1 units, OR = 0.41, 95% CI: 0.28, 0.60) and decreased latency (per 0.1 units, OR = 0.55, 95% CI: 0.39, 0.78). Further research is necessary to understand how these and other exposures (e.g., diet) perturb an individuals’ inherited sleep patterns and contribute to downstream health outcomes.

Non-steroidal Anti-inflammatory Drug Use and Risk of Age-Related Macular Degeneration in the California Teachers Study.

PurposeThe aim of this study was to examine whether use of regular aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs) is associated with the development of age-related macular degeneration (AMD).MethodsIn the California Teachers Study cohort (N = 88,481) we identified diagnoses of AMD up to December 31, 2012 by linkage to statewide hospital discharge records. Aspirin, ibuprofen, other NSAIDs, and acetaminophen use and comprehensive risk factor information were collected via self-administered questionnaires at baseline in 1995–1996 and a follow-up questionnaire in 2005–2006. We employed Cox proportional hazard regression to model AMD risk.ResultsWe did not find any associations between AMD and frequency and duration of aspirin or ibuprofen use reported at baseline. In the subsample with more specific information on medication use, we observed a 20% decrease in risk of AMD among low-dose aspirin users (HR 0.81, 95% CI 0.70–0.95) and a 55% decrease among cyclooxygenase-2 (COX-2) inhibitor users (HR 0.45, 95% CI 0.26–0.78) during 6.3 years of average follow-up.ConclusionThe decrease in risk of intermediate- or late-stage AMD among women who reported regular use of low-dose aspirin or specific COX-2 inhibitors suggests a possible protective role for medications with COX-2 inhibitory properties or aspirin at doses used for cardiovascular disease prevention.

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

ABSTRACT 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.

Outdoor artificial light at night, non-Hodgkin lymphoma, and the California Teachers Study cohort

Background: Circadian disruption has been implicated in a growing number of adverse health outcomes. Circadian disruptions due to outdoor artificial light at night (ALAN) have been associated with increased circulating levels of inflammation; a hallmark of cancer. We examined the association between outdoor ALAN and a cancer strongly associated with autoimmune and inflammatory conditions, non-Hodgkin lymphoma (NHL), in the prospective California Teachers Study (CTS) cohort. Methods: The CTS is a large prospective cohort of 133,477 women that were active or retired teachers and members of the California State Teachers Retirement System in 1995-96. Outdoor ALAN was assigned to participant addresses reported at study baseline through use of the New World Atlas of Artificial Night Sky Brightness. Among 105,937 women followed from 1995-2015, linkage to the California Cancer Registry identified 873 incident cases of NHL. Age-stratified Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for overall NHL and the most common NHL subtypes; diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In multivariate analyses, we adjusted for subtype specific covariates (e.g. body mass index (BMI) for DLBCL). Results: Compared to residents in the lowest quintile, participants residing in the highest quintile of outdoor ALAN were more likely to develop NHL overall (HR 1.32, 95% CI 1.07-1.63), and, in particular, DLBCL (HR 1.87, 95% CI 1.16-3.02). The elevated risk for DLBCL remained statistically significant after adjusting for age, race/ethnicity, BMI, and socioeconomic status (DLBCL:HR 1.70, 95% CI 1.03-2.79, NHL:HR 1.32, 95% CI 1.06-1.65). There was no association between ALAN and FL or CLL/SLL. Conclusions: Increased DLBCL risk was observed among women residing in neighborhoods with higher levels of outdoor ALAN. Future research in circadian disruption and DLBCL may clarify potential biological processes implicated in this association.

Outdoor artificial light at night and risk of non-Hodgkin lymphoma among women in the California Teachers Study cohort

BackgroundOutdoor artificial light at night (ALAN) has been implicated in a growing number of adverse health outcomes. ALAN is believed to disrupt circadian rhythms and has been associated with increased inflammation, one of the hallmarks of cancer. We examined the association between outdoor ALAN and a cancer strongly associated with autoimmune and inflammatory conditions, non-Hodgkin lymphoma (NHL), in the prospective California Teachers Study cohort. MethodsOutdoor ALAN was assigned to participant addresses at study baseline (1995−96) through use of the New World Atlas of Artificial Night Sky Brightness. Among 105,937 women followed from 1995 to 2015, linkage to the California Cancer Registry identified 873 incident cases of NHL. Age-stratified Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % confidence intervals (95 %CI) for overall NHL and the most common NHL subtypes; diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Multivariate analyses adjusted for previously reported subtype specific covariates (e.g. body mass index (BMI) for DLBCL). ResultsCompared to the lowest quintile, participants residing in the highest quintile of outdoor ALAN at baseline were more likely to develop NHL (HR = 1.32, 95 %CI = 1.07−1.63), and, in particular, DLBCL (HR = 1.87, 95 %CI = 1.16−3.02). The elevated risk for DLBCL remained statistically significant after adjusting for age, race/ethnicity, BMI, and socioeconomic status (DLBCL:HR = 1.87, 95 %CI = 1.16−3.02, NHL:HR = 1.32, 95 %CI = 1.07−1.63). There was no association between ALAN and FL or CLL/SLL. ConclusionDLBCL risk was elevated among women residing in neighborhoods with greater outdoor ALAN. Future research in circadian disruption and DLBCL may clarify potential biological processes implicated in this association.

0383 Outdoor Artificial Light at Night, Sleep Duration, and Sleep Quality in the California Teachers Study Cohort

Abstract Introduction Artificial light at night (ALAN) is believed to disrupt sleep by suppressing melatonin and altering normal circadian patterns. We assessed the association between self-reported sleep measures and outdoor ALAN in a large cohort of women. Methods The California Teachers Study (CTS) is a prospective cohort of 133,479 current and former Californian female public school professionals recruited and given a baseline questionnaire in 1995-1996. A follow-up questionnaire in 2012-2014 assessed self-reported measures of sleep habits, quality, and chronotype. Using geocoded residential addresses, participants were assigned exposures to outdoor ALAN based on the New World Atlas of Artificial Night Sky Brightness to assess the association between ALAN and self-reported sleep initiation, duration, and quality. Results Of the 42,706 women who completed the follow-up questionnaire and reported the same sleep patterns over the previous year, 5,968 reported poor sleep quality. The median outdoor ALAN was 2.16 (IQR: 1.04-3.61) millicandela per meter squared (mcd/m2). After adjusting for self-reported chronotype, use of sleep medication, age, race, and socioeconomic status, residing in the highest ALAN quintile was associated with poor sleep (OR 1.16, 95% CI 1.07-1.26). There did not appear to be an association between outdoor ALAN and time taken to fall asleep (OR 1.02, 95% CI 0.96-1.08), but it was associated with sleeping less than 8 hours (OR 1.41, 95% CI 1.33-1.50). Conclusion CTS participants who self-reported shorter sleep and poorer sleep quality were more likely to reside in areas with greater levels of outdoor ALAN. We did not see an association with ALAN and time to fall asleep, suggesting ALAN may be contributing to later sleep time or earlier waking. As we continue to follow this cohort, the data collected over the past 20 years provide a rich resource for studying both factors related to sleep and its effect on health. Support The California Teachers Study and the research reported in this publication were supported by the National Cancer Institute of the National Institutes of Health under award number U01-CA199277; P30-CA033572; P30-CA023100; UM1-CA164917; R01-CA077398; and R01-CA207020.

Physical Activity, Hormone Therapy Use, and Stroke Risk among Women in the California Teachers Study Cohort

Background: Postmenopausal hormone therapy (HT) increases the risk of stroke. Here we evaluate whether leisure time physical activity (LTPA) can change stroke risk in women using HT, leveraging data from the California Teachers Study. Methods: Female California educators without a prior history of stroke (n = 118,294) were followed from 1995 through 2015 for stroke end points. Based on statewide hospitalization data, 4,437 women had ischemic (n = 3,162; International Classification of Diseases [ICD]-9 433, 434, 436) or hemorrhagic (n = 1,275; ICD-9 430–432, excluding 432.1) stroke. LTPA and HT use were evaluated at 2 time points (baseline [1995–1996] and 10-year follow-up [2005–2006]). LTPA was assessed using American Heart Association (AHA) recommendations (>150 min/week moderate or >75 min/week strenuous physical activity). Using multivariable Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% CIs for the associations between HT use and concurrent LTPA with incident stroke. Results: Compared to women who never used HT, stroke risk was highest among women who were current HT users and did not meet AHA recommendations for LTPA at the time of their HT use: HR_baseline 1.28 (95% CI 1.13–1.44); HR_{10-year follow-up} 1.17 (95% CI 0.91–1.50). Based on the baseline questionnaire, current HT users who met AHA recommendations for LTPA in 1995–1996 still had elevated stroke risk in the 20-year follow-up (HR 1.22, 95% CI 1.08–1.37). However, among current HT users who met AHA recommendations for LTPA at the 2005–2006 follow-up questionnaire, stroke risk was not elevated (HR 1.01, 95% CI 0.80–1.29). Evaluation of the 2 time points in concert further demonstrated that meeting AHA recommendations for LTPA at the most recent follow-up time point was required to reduce HT-related stroke risk. Conclusion: Concurrent physical activity may attenuate the short-term increase in risk of stroke risk associated with HT use.

Hypertension, antihypertensive medications use and risk of age-related macular degeneration in California Teachers Cohort.

Sustained and inadequately controlled hypertension can promote the development of age-related macular degeneration (AMD) through multiple biologic pathways. Epidemiologic studies of high blood pressure, antihypertensive therapies, and the risk of AMD thus far have been inconclusive. However, few studies evaluated risks according to the use of different classes of antihypertensive drugs or took combinations of use into account. We performed a prospective cohort study by linking the California Teachers Study (CTS) cohort (N = 88 481) to statewide hospital discharge records up to December 31, 2012. History of high blood pressure, regular use of antihypertensive medications, and comprehensive risk factor information was collected via self-administered questionnaires at baseline in 1995-1996, and information on specific classes of antihypertensive drugs was provided by a subsample of CTS participants who completed a follow-up questionnaire in 2000. We identified 1762 female teachers with AMD during 14.8 years of follow-up on average. Applying Cox proportional hazard regression, we estimated increased risks of AMD among women treated for hypertension at baseline (HR = 1.15, 95% CI: 1.03, 1.30); the magnitude of the association increased with longer duration of antihypertensive treatment. In the subsample with more specific information on type of medication use, we estimated a 45% increased risk of AMD among women receiving diuretics as monotherapy compared to women with medications more potent than diuretics (HR = 1.45, 95% CI 1.10, 1.90). In women treated with a combination of antihypertensive drugs, we observed no increased risk of AMD for any individual class of drugs.

Diet Quality Scores Inversely Associated with Postmenopausal Breast Cancer Risk Are Not Associated with Premenopausal Breast Cancer Risk in the California Teachers Study

BackgroundEvidence for the association between diet and breast cancer risk is inconsistent Thus, research that compares indexes of overall diet quality may provide new insight. ObjectiveWe examined the association between diet quality indexes and pre- and postmenopausal breast cancer risk in a large prospective cohort. MethodsThis was a prospective analysis of 96,959 women, aged 22–104 y, in the California Teachers Study cohort (1995–2011). Diet quality was characterized by 4 different indexes. Specifically, we examined Alternate Mediterranean Diet (aMED), Alternative Healthy Eating Index–2010 (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH), and Paleolithic index (PALEO) scores with the risk of developing breast cancer. We used multivariable Cox proportional hazards regression models to derive HRs and 95% CIs for breast cancer risk. ResultsIn the analysis of 42,517 women at risk of premenopausal breast cancer, there was no association between any of the indexes and incident breast cancer (346 cases). In the analysis of 54,442 women at risk of postmenopausal breast cancer at baseline, higher AHEI-2010, aMED, and DASH scores were inversely associated with incident breast cancer (3523 incident cases). Respectively, HRs (95% CIs) comparing quintile 5 to quintile 1 (reference) for AHEI-2010, aMED, and DASH indexes were 0.87 (0.78, 0.97; P-trend = 0.004), 0.91 (0.82, 1.02; P-trend = 0.03), and 0.89 (0.80, 1.00; P-trend = 0.03). The PALEO score was not associated with postmenopausal breast cancer (HR for quintile 5 compared with quintile 1: 1.05; 95% CI: 0.94, 1.17). ConclusionsDiet quality indexes that emphasize intake of whole grains, vegetables, fruits, legumes, and nuts and seeds and de-emphasize red and processed meats and sugar-sweetened beverages were modestly associated with a lower risk of incident postmenopausal breast cancer risk. However, they were not associated with premenopausal breast cancer, and the PALEO score was not associated with cancer risk regardless of menopausal status.

Exploring Environmental Chemicals and Risk of Breast Cancer during the Menopausal Transition

Teasing out the biologic mechanisms of endocrine-disrupting chemicals (EDCs) in epidemiologic studies is complicated given their heterogeneity, and assessing the effects of exposures in vitro assays and in vivo animal studies may not reflect what happens in human populations. Therefore, using a transdisciplinary approach with a population-based epidemiologic study, in vitro assays, and in vivo mouse models, offers a targeted opportunity to evaluate the role of EDCs in promoting breast cancer during the menopausal transition. We are specifically investigating the effects of three polybrominated diphenyl ethers (BDE-47, BDE-100, and BDE-153). Using blood samples collected during the menopausal transition from women in the prospective California Teachers Study (CTS) cohort, we are assessing the effects of PBDE levels on the epigenome through miRNA and global and gene methylation assays, on total estrogenic activity, and on risk of developing breast cancer. In in vitro experiments in breast cell lines, we are measuring the effects of PBDEs at a range of levels, including at the CTS serum levels, to assess their effects on the activity of the estrogen and progesterone receptors and aromatase, as well as on the epigenome, transcriptome, and cell proliferation. Initial results suggest that BDE-47 acts as a mild ER-&amp;#945; agonist and BDE-100 and BDE-153 act as weak antagonists. In in vivo mouse models, we are testing whether combined effects of PBDEs at the levels seen in serum of the CTS samples cause mammary gland lesions. We first are studying ovariectomized mice, which have minimal estrogenic activity in their bodies, and then will use an ovarian-failure mouse model to represent the menopausal transition. Definitive changes in uterus weight and gene expression profiles have been observed in mice following 1-week feeding of PBDE-containing diet.

Genome-Wide Testing of Exonic Variants and Breast Cancer Risk in the California Teachers Study.

Background: Few studies have focused on the relationship of exonic variation with breast cancer and subtypes defined by tumor markers: estrogen receptor (ER), progesterone receptor (PR), and HER2.Methods: We genotyped 1,764 breast cancer patients and 1,400 controls from the California Teachers Study cohort using the Infinium HumanExome Beadchip. Individual variant and gene-based analyses were conducted for overall breast cancer and by individual tumor marker subtype.Results: No exonic variants or gene-based analyses were statistically significantly associated with breast cancer overall or by ER-, PR-, or HER2-defined subtype.Conclusions: We did not detect any novel statistically significant exonic variants with overall breast cancer risk or by subtype.Impact: Exonic variants in the exome chip may not be associated with overall breast cancer or subtype susceptibility. Cancer Epidemiol Biomarkers Prev; 26(9); 1462-5. ©2017 AACR.

Functional IGF1R variant predicts breast cancer risk in women with preeclampsia in California Teachers Study

PurposeHypertension in pregnancy has been associated with decreased future risk of breast cancer in many but not all studies. In the Marin Women’s Study, pregnancy-induced hypertension was shown to interact with the T allele of a functional IGF1R gene variant, rs2016347, to result in lower breast density, as well as decreased breast cancer risk. Our objective was to explore these findings in a larger sample of women from the California Teachers Study (CTS).MethodsThe CTS cohort consists of over 130,000 female educators. DNA was available from a nested case–control study, which included 2,030 non-Hispanic white women who developed breast cancer and 1,552 controls. The current study included all participants from the case–control group with a self-reported history of preeclampsia (80 cases/57 controls).ResultsComparing TT to GG genotypes revealed adjusted odds ratios of 0.38 (CI 0.13, 1.14) for all invasive breast cancers, 0.26 (CI 0.07, 0.89) for hormone receptor-positive (HR+) breast cancers, 0.15 (CI 0.04, 0.56) for those with age at first birth (AFB) < 30, and 0.10 (CI 0.02, 0.49) for those with AFB < 30 and HR+ breast cancers. Trend analysis yielded p values of 0.09, 0.03, 0.005, and 0.004 respectively, suggesting a biological effect for each T allele.ConclusionStudy findings indicate that the T allele of IGF1R variant rs2016347 is associated with a significant reduction in breast cancer risk in women with a history of preeclampsia, most marked for HR+ breast cancer and in women with AFB < 30.

Lifetime body size and estrogen-receptor-positive breast cancer risk in the California Teachers Study cohort.

BackgroundObesity is a public health epidemic and an important breast cancer risk factor. The relationship between interrelated body measurements is complex and most studies fail to account for this complexity. We identified key aspects of body size which jointly, over the life-course (since adolescence), are associated with estrogen-receptor-positive (ER+) breast cancer risk.MethodsAmong 109,862 women participating in the California Teachers Study cohort, 3844 were diagnosed with invasive ER+ breast cancer between 1997–1998 and December 2011. Based on validated self-reported height and weight at age 18, baseline, and 10-year follow up and waist circumference at 2-year and 10-year follow up, we identified 16 a priori body-size phenotypes. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI).ResultsPremenopausal breast cancer was influenced by adolescent, but not adult, body size (HR = 0.51, 95% CI 0.31–0.86 for body mass index (BMI; kg/m2) ≥25 vs <20 at age 18). Among postmenopausal women currently using hormone therapy, only those with the greatest body size had increased breast cancer risk (HR = 1.36, 95% CI 1.13–1.64 for height ≥67 inches and adult BMI ≥25 vs height <67). Among postmenopausal women not currently using hormone therapy, the relationship between body size and risk was complex, with the largest effects of adiposity among short women. Among short women, those with gluteal adiposity (HR = 2.70, 95% CI 1.77–4.10) and those who continued to gain weight throughout adulthood (HR = 2.57, 95% CI 1.60–4.12) were at greatest risk, whereas those who had been overweight/obese since adolescence were not at increased risk (HR = 1.33, 95% CI 0.84–2.10). Height was associated with a small increased risk, with borderline statistical significance.ConclusionsConsidering absolute body mass in adolescence and at two points in adulthood, dynamic changes in adiposity over time, and body fat distribution, we identified obesity phenotypes associated with ER+ breast cancer risk. Our approach more clearly identifies specific risk groups than do analyses that evaluate similar measures separately. These findings may aid in improving risk prediction models and developing targeted interventions, and may clarify inconsistent findings across studies.

Indicators of microbial-rich environments and the development of papillary thyroid cancer in the California Teachers Study

BackgroundLittle epidemiologic research has focused on the role of immune function in papillary thyroid cancer risk despite scattered observations suggesting it may be important (e.g., hygiene hypothesis). Here we investigate papillary thyroid cancer risk associated with self-reported living environments across the lifespan reflecting immunologically relevant exposures to microbial-rich environments. MethodsAmong 61,803 eligible participants in the California Teachers Study cohort, 100 were diagnosed with invasive papillary thyroid cancer between 2005 and 2012. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). ResultsLiving in a rural area during early childhood was associated with significantly reduced risk of developing papillary thyroid cancer as an adult (HR=0.51, 95% CI: 0.28–0.94). Specifically, reduced risks were observed for living within a half mile of hoofed animals (HR=0.47, 95% CI: 0.26–0.84), as was having an indoor dog or cat (HR=0.51, 95% CI: 0.32–0.80). Neither sharing a bedroom or living in a rented home as a child nor attending daycare or kindergarten was associated with reduced risk. ConclusionsEarly childhood exposures to hoofed animals or indoor furry pets were associated with reduced risk of subsequently developing papillary thyroid cancer. ImpactOur findings point to immunologically relevant, early-life exposures to microbial-rich environments as potentially important in reducing thyroid cancer risk, consistent with the hygiene hypothesis and suggesting that certain, possibly animal-derived, microbial exposures may be important to immune calibration or priming.