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BackgroundThere is growing evidence that exposure to low-grade inflammation may be associated with adverse health outcomes.MethodsWe 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.ResultCompared 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.ConclusionsSeveral 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.

BackgroundCadmium (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.ObjectivesTo determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development.MethodsA 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.ResultsThe 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

PurposePolybrominated diphenyl ethers (PBDEs) are among the most persistent and pervasive global environmental contaminants. Their toxic and endocrine-disrupting properties have made them a focus of concern for breast cancer. Our objective was to evaluate the risk of breast cancer associated with serum PBDE levels in a case-control study nested within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 936 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed between 2011 and 2015. Blood samples were collected from cases an average of 35 months after diagnosis. PBDEs were measured in serum using automated solid phase extraction and gas chromatography/high resolution mass spectrometry. Statistical analyses were restricted to the three congeners with detection frequencies ≥75%: 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CI) for each BDE congener, adjusting for serum lipids and other potential confounders.ResultsThe OR for each of the three BDE congeners was close to unity with a CI that included one. Analyses stratified by menopausal status, tumor hormone responsiveness, BMI, and changes in body weight yielded similarly null results.ConclusionsOur findings provide no evidence that serum levels of BDE-47, BDE-100 or BDE-153 are associated with breast cancer risk. These results should be interpreted in the context of study limitations which include the reliance on PBDE measurements that may not represent pre-diagnostic, early-life or chronic exposures and a lack of information on genetic polymorphisms and other factors which may affect endogenous estrogen levels.

BackgroundPer- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011-2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS.ResultsFor all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs

After several decades of widespread use, some per- and polyfluoroalkyl substances (PFASs) were phased-out of use due to concerns raised by their persistent, bioaccumulative, and toxic properties. Our objective was to evaluate temporal trends in serum PFAS levels among 1257 middle-aged and older California women (ages 40-94) during a four year period, beginning approximately 5-10 years after these phase-outs began. An online SPE-HPLC-MS/MS was used to measure 10 long-chain PFASs in serum from blood collected cross-sectionally during 2011-2015 from a subset of participants in the California Teachers Study. Results from multivariable linear regression analyses indicated that serum concentrations of nearly all PFASs declined on average 10% to 20% per year. Serum levels of perfluorohexanesulfonic acid (PFHxS) did not significantly decline. With the exception of PFHxS, the downward trend in serum concentrations was evident for all PFASs across all ages, although declines were comparatively steeper among the oldest women. These findings suggest that the phase-out of some common PFASs has resulted in reduced human exposures to them. The lack of a decline for PFHxS suggests that these exposures may be ongoing and underscores the importance of continued biomonitoring and research efforts to elucidate current pathways of exposure.

Melanoma incidence has been increasing in light-skinned populations worldwide, but the reasons for the increase have been controversial. Our prior assessment in California non-Hispanic whites showed substantial increases in invasive melanoma incidence for tumors of all thicknesses in all neighborhoods categorized by socioeconomic status (SES) between 1988-1992 and 1998-2002. To understand whether these trends continued, we updated our assessment to include the diagnosis period 2008-2012 and more accurate pathologic stage at diagnosis. We used the California Cancer Registry to calculate age-adjusted incidence rates for over 58,000 newly diagnosed melanomas. Incidence rates not only continued to rise over the 10-year period from 1998-2002 and 2008-2012 but also showed significant increases in almost all groups defined jointly by tumor thickness or stage at diagnosis and a small area (census tract) SES measure. The largest relative rate increases were seen for regional, distant, and ulcerated disease, especially among males living in the lowest SES neighborhoods. Considering tumor thickness and stage as proxies for time to screening detection and neighborhood SES as a proxy for health care access, we interpret this pattern to indicate continued, true increases in melanoma occurrence as opposed to a thin tumor phenomenon simply driven by improved access to care.

BackgroundAlthough married cancer patients have more favorable survival than unmarried patients, reasons underlying this association are not fully understood. The authors evaluated the role of economic resources, including health insurance status and neighborhood socioeconomic status (nSES), in a large California cohort.MethodsFrom the California Cancer Registry, we identified 783,167 cancer patients (386,607 deaths) who were diagnosed during 2000 through 2009 with a first primary, invasive cancer of the 10 most common sites of cancer-related death for each sex and were followed through 2012. Age-stratified and stage-stratified Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality associated with marital status, adjusted for cancer site, race/ethnicity, and treatment.ResultsCompared with married patients, unmarried patients had an elevated risk of mortality that was higher among males (HR, 1.27; 95% CI, 1.26-1.29) than among females (HR, 1.19; 95% CI, 1.18-1.20; Pinteraction < .001). Adjustment for insurance status and nSES reduced the marital status HRs to 1.22 for males and 1.15 for females. There was some evidence of synergistic effects of marital status, insurance, and nSES, with relatively higher risks observed for unmarried status among those who were under-insured and living in high nSES areas compared with those who were under-insured and living in low nSES areas (Pinteraction = 6.8 × 10(-9) among males and 8.2 × 10(-8) among females).ConclusionsThe worse survival of unmarried than married cancer patients appears to be minimally explained by differences in economic resources. Cancer 2016;122:1618-25. © 2016 American Cancer Society.

BackgroundIt has been observed that married cancer patients have lower mortality rates than unmarried patients, but data for different racial/ethnic groups are scarce. The authors examined the risk of overall mortality associated with marital status across racial/ethnic groups and sex in data from the California Cancer Registry.MethodsCalifornia Cancer Registry data for all first primary invasive cancers diagnosed from 2000 through 2009 for the 10 most common sites of cancer-related death for non-Hispanic whites (NHWs), blacks, Asians/Pacific Islanders (APIs), and Hispanics were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for marital status in relation to overall mortality by race/ethnicity and sex. The study cohort included 393,470 male and 389,697 female cancer patients and 204,007 and 182,600 deaths from all causes, respectively, through December 31, 2012.ResultsAll-cause mortality was higher in unmarried patients than in married patients, but there was significant variation by race/ethnicity. Adjusted HRs (95% CIs) ranged from 1.24 (95% CI, 1.23-1.26) in NHWs to 1.11 (95% CI, 1.07-1.15) in APIs among males and from 1.17 (95% CI, 1.15-1.18) in NHWs to 1.07 (95% CI, 1.04-1.11) in APIs among females. All-cause mortality associated with unmarried status compared with married status was higher in US-born API and Hispanic men and women relative to their foreign-born counterparts.ConclusionsFor patients who have the cancers that contribute most to mortality, being unmarried is associated with worse overall survival compared with being married, with up to 24% higher mortality among NHW males but only 6% higher mortality among foreign-born Hispanic and API females. Future research should pursue the identification of factors underlying these associations to inform targeted interventions for unmarried cancer patients. Cancer 2016;122:1570-8. © 2016 American Cancer Society.

BackgroundEspecially for cancers with long latency periods, such as breast cancer, the issue of residential mobility hinders ecologic analyses seeking to examine the role of environmental contaminants in chronic disease etiology. This study describes and evaluates characteristics associated with residential mobility in a sub-sample of the California Teachers Study (CTS) cohort.MethodsIn 2000, lifetime residential histories were collected for a sub-sample of 328 women enrolled in the CTS; women's degree of residential mobility and associated factors were analyzed.ResultsWhile most women moved many times during their lives (average = 8.9), the average number of years at their residence when they enrolled in the study was reasonably long (15.1 years). Age strongly predicted duration at current residence but was not related to the number of lifetime residences. After adjusting for age, California-born women and women living in high socioeconomic status (SES) neighborhoods were significantly more residentially stable. Agreement between self-reported urbanization of recent residences and that based on census data of the geocoded residences was very good (80% concordant). Among women currently living in urban areas, an average of 43.3 years, or 77%, of their lifetimes were spent in urban residences; among women currently living in a rural area, an average of 37.3 years, or 67% of their lifetimes were spent in rural residences.ConclusionsThis suggests that analyses of incidence rates based on current residence, while not capturing a woman's full exposure history, may reasonably reflect some aspect of longer term chronic exposures, especially those related to urbanization, at least in professional women.

We examined the association between residential proximity to agricultural pesticide use and breast cancer incidence among members of the California Teachers Study cohort, a large study of professional school employees with extensive information on breast cancer risk factors, followed for cancer incidence since 1995. We identified 1552 invasive breast cancer cases, diagnosed between 1996 and 1999, among 114,835 cohort members. We used California Pesticide Use Reporting data to select pesticides for analysis based on use volume, carcinogenic potential, and exposure potential; a Geographic Information System was used to estimate pesticide applications within a half-mile radius of subjects' residences. We applied Cox proportional hazard models to estimate hazard rate ratios (HR) for selected pesticides, adjusting for age, race, and socioeconomic status. We saw no association between residential proximity to recent agricultural pesticide use and invasive breast cancer incidence. HR estimates for the highest compared to the lowest exposure categories for groups of agents were as follows: probable or likely carcinogens (1.07, 95% confidence interval (CI): 0.86-1.32), possible or suggestive carcinogens (1.06, 95% CI: 0.87-1.29), mammary carcinogens (1.15, 95% CI: 0.90-1.48), and endocrine disruptors (1.03, 95% CI: 0.86-1.25). HR estimates for other groups and individual pesticides did not differ from unity, nor was there a trend for any groupings of or individual pesticides examined. Stratifying by menopausal status or family history of breast cancer did not substantially affect our results. Our analyses suggest that breast cancer incidence is not elevated in areas of recent, high agricultural pesticide use in California.

ObjectivesThese analyses were designed to describe characteristics associated with active and passive smoking in a large cohort of women in order to identify possible confounders of the relationship between smoking exposures and breast cancer risk.MethodsAnalyses were based on 1995 data collected from the California Teachers Study (CTS) and were restricted to those with complete and usable tobacco data (n = 128,174). Age-adjusted and race-adjusted odds ratios (OR) were generated by unconditional logistic regression.ResultsCompared with never smokers, both current and former smokers experienced menarche at an earlier age. Current and former smokers also were more likely than their never smoking counterparts to be nulliparous. Among parous women, current, but not former smokers were less likely than never smokers to have had their first child at an older age. Similarly, among never smokers, those exposed to household passive smoking experienced menarche at an earlier age, were more likely to be nulliparous, and among parous women, were less likely to have had their first child at an older age than never smokers not exposed to passive smoking. Greater alcohol consumption was strongly associated with both active and passive smoking exposures. Compared with never smokers, current smokers were less likely to take antioxidant supplements, whereas former smokers were more likely to take antioxidant supplements. Among never smokers, antioxidant use did not differ depending on passive smoking exposure. A number of other dietary correlates of active and passive smoking were identified.ConclusionsWe identified a number of reproductive and dietary correlates to smoking exposures that underscore the need to adjust for such factors in an analysis of smoking and breast cancer and potentially other disease entities. Furthermore, these findings may suggest potential mechanisms underlying an association between breast cancer and smoking.

PurposeThis study describes the prevalence and patterns of environmental tobacco smoke (ETS) exposure in a large, well-defined cohort of professional, female school employees in California.DesignThis is a cross-sectional study based on survey responses from members of the California Teachers Study (CTS) cohort.SubjectsThe analyses focused on lifetime nonsmokers (N = 61,899) in the CTS cohort who responded to detailed questions on lifetime ETS exposures in the home, workplace, and other social settings.MeasuresDemographic characteristics, smoking status, and ETS exposure were based on self-reported data from two mailed surveys. Prevalence estimates within the cohort were compared with those from the California Behavioral Risk Factor Survey and the California Adult Tobacco Survey.ResultsETS exposures were highest for never smokers born in the 1930s (78% in the home, 66% in the workplace, and 48% in other social settings) and steadily declined among participants born in later years. ETS exposure from spousal smoking peaked during the 1950s (37%). In the 1980s, the workplace (28%) replaced the household (19%) as the primary exposure setting.ConclusionsConsideration of these patterns in the prevalence of ETS exposures is important in the interpretation and design of tobacco-related health studies.

BackgroundThere is great interest in whether exposure to tobacco smoke, a substance containing human carcinogens, may contribute to a woman's risk of developing breast cancer. To date, literature addressing this question has been mixed, and the question has seldom been examined in large prospective study designs.MethodsIn a 1995 baseline survey, 116 544 members of the California Teachers Study (CTS) cohort, with no previous breast cancer diagnosis and living in the state at initial contact, reported their smoking status. From entry into the cohort through 2000, 2005 study participants were newly diagnosed with invasive breast cancer. We estimated hazard ratios (HRs) for breast cancer associated with several active smoking and household passive smoking variables using Cox proportional hazards models.ResultsIrrespective of whether we included passive smokers in the reference category, the incidence of breast cancer among current smokers was higher than that among never smokers (HR = 1.32, 95% confidence interval [CI] = 1.10 to 1.57 relative to all never smokers; HR = 1.25, 95% CI = 1.02 to 1.53 relative to only those never smokers who were unexposed to household passive smoking). Among active smokers, breast cancer risks were statistically significantly increased, compared with all never smokers, among women who started smoking at a younger age, who began smoking at least 5 years before their first full-term pregnancy, or who had longer duration or greater intensity of smoking. Current smoking was associated with increased breast cancer risk relative to all nonsmokers in women without a family history of breast cancer but not among women with such a family history. Breast cancer risks among never smokers reporting household passive smoking exposure were not greater than those among never smokers reporting no such exposure.ConclusionOur study provides evidence that active smoking may play a role in breast cancer etiology and suggests that further research into the connection is warranted, especially with respect to genetic susceptibilities.