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1.  Risk of colorectal cancer associated with active smoking among female teachers 
Cancer causes & control : CCC  2013;24(7):1291-1304.
Purpose
The objective of this study was to examine the risk of colorectal cancer associated with active smoking among members of the California Teachers Study (CTS), a large cohort of female public school employees for whom highly detailed smoking information is available.
Methods
The analysis was conducted among the 122,264 CTS participants who lived in California at cohort entry in 1995/1996, had no prior history of colorectal cancer, and provided detailed smoking information. 1,205 cases of invasive colorectal cancer prospectively diagnosed in 1995–2009 were identified from the California Cancer Registry, including 650 in the proximal colon, 267 in the distal colon, and 288 in the rectum. Hazard ratios and 95 % confidence intervals were estimated using Cox proportional hazards models, stratified by age at cohort entry, and adjusted for race/ethnicity.
Results
Compared to never smokers, current smokers had an approximately 30 % increased risk of colorectal cancer. Overall, a slightly elevated risk was also noted for former smokers. Among former smokers, risks appeared to remain elevated for up to 20 years following cessation. Risks among former and current smokers increased with greater intensity and duration of smoking. Little evidence for heterogeneity in risk was noted for colon versus rectal cancer or for different subsites within the colon.
Conclusions
These results provide convincing evidence that heavy and/or long-term smoking is a risk factor for cancers of the colon and rectum. Such evidence should be considered when updating screening guidelines to include targeting people with long active smoking histories.
doi:10.1007/s10552-013-0207-z
PMCID: PMC3733091  PMID: 23572327
Smoking; Colorectal cancer; Colon cancer; Rectal cancer; Risk; Women
2.  Increased long-term recreational physical activity is associated with older age at natural menopause among heavy smokers: the California Teachers Study 
Menopause (New York, N.Y.)  2013;20(3):282-290.
Objective
Although physical activity modulates the hypothalamic-ovarian-pituitary axis, the few studies investigating whether physical activity is associated with age at natural menopause have had mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women, overall, and by smoking history.
Methods
We investigated the association between long-term physical activity (hours/week/year) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former-light smoker, former-heavy smoker, current-light smoker, current-heavy smoker) as an effect modifier was evaluated.
Results
In a multivariable model adjusting for body mass index at age 18, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (ptrend=0.005). Higher body mass index at age 18 (ptrend=0.0003) and older age at menarche (ptrend=0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs. non-Hispanic whites, HR 1.17, 95% CI 1.09–1.26), current smokers (vs. never smokers, HR 1.68, 95% CI 1.60–1.75 for current-light smokers; HR 1.38, 95% CI 1.33–1.44 for current-heavy smokers) and older age at first full-term pregnancy (HR≥29, 2+ full-term pregnancies vs. <29, 2+ full-term pregnancies 1.10, 95% CI 1.06–1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older natural menopause among heavy smokers only (HRHighest vs. Lowest quartile 0.88, 95% CI 0.81–0.97, ptrend=0.02 for former-heavy smokers; HRHighest vs. Lowest quartile 0.89, 95% CI 0.80–0.99, ptrend=0.04 for current-heavy smokers).
Conclusion
Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.
doi:10.1097/GME.0b013e31826ce3d4
PMCID: PMC3580010  PMID: 23435025
Physical activity; smoking status; age at natural menopause; reproductive factors; cohort studies
3.  Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study 
Cancer epidemiology  2012;37(1):46-53.
Purpose
Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women.
Methods
116,939 women in the California Teachers Study, aged 22 to 79 years with no history of thyroid cancer at cohort entry, were followed from 1995-1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort).
Results
Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR=0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI<25.0 kg/m2, trend p=0.03) than among overweight or obese women (trend p=0.35; homogeneity-of-trends p=0.03). A similar pattern of risk was observed for recent activity (BMI<25 kg/m2, trend p=0.11; BMI≥25 kg/m2, trend p=0.16; homogeneity-of-trends p=0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood).
Conclusions
Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women.
doi:10.1016/j.canep.2012.09.003
PMCID: PMC3543486  PMID: 23116823
Physical activity; thyroid cancer; cancer prevention; women; overweight/obesity; Body Mass Index
4.  Alcohol consumption and breast cancer risk among postmenopausal women following the cessation of hormone therapy use: the California Teachers Study 
Background
Alcohol consumption increases breast cancer risk, but its effect may be modified by hormone therapy (HT) use, such that exposure to both may be synergistic. Because many women stopped taking HT after mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today.
Methods
Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI).
Results
Increased breast cancer risk associated with alcohol consumption was observed among postmenopausal women who were current HT users (RR=1.60, 95% CI: 1.13–2.26 and RR=2.11, 95% CI: 1.41–3.15 for <20 and ≥20 g/d of alcohol), with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3–4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for ER+ and ER+PR+ tumors; while power was limited, no increase in risk was observed for ER- tumors.
Conclusions
Following the cessation of HT use, alcohol consumption is not significantly associated with breast cancer risk, although a non-significant increased risk was observed among women who never used HT.
Impact
Our findings confirm that concurrent exposure to HT and alcohol has a substantial adverse impact on breast cancer risk. However, after HT cessation, this risk is reduced.
doi:10.1158/1055-9965.EPI-12-0418
PMCID: PMC3721729  PMID: 22832206
breast cancer; alcohol; hormone therapy; cessation; epidemiology
6.  A cross-sectional analysis of light at night, neighborhood sociodemographics and urinary 6-sulfatoxymelatonin concentrations: implications for the conduct of health studies 
Background
There is accumulating evidence that circadian disruption, mediated by alterations in melatonin levels, may play an etiologic role in a wide variety of diseases. The degree to which light-at-night (LAN) and other factors can alter melatonin levels is not well-documented. Our primary objective was to evaluate the degree to which estimates of outdoor environmental LAN predict 6-sulftoxymelatonin (aMT6s), the primary urinary metabolite of melatonin. We also evaluated other potential behavioral, sociodemographic, and anthropomorphic predictors of aMT6s.
Methods
Study participants consisted of 303 members of the California Teachers Study who provided a 24-hour urine specimen and completed a self-administered questionnaire in 2000. Urinary aMT6s was measured using the Bühlmann ELISA. Outdoor LAN levels were estimated from satellite imagery data obtained from the U.S. Defense Meteorological Satellite Program’s (DMSP) Operational Linescan System and assigned to study participants’ geocoded residential address. Information on other potential predictors of aMT6s was derived from self-administered surveys. Neighborhood socioeconomic status (SES) was based on U.S. Census block group data.
Results
Lower aMT6s levels were significantly associated with older age, shorter nights, and residential locations in lower SES neighborhoods. Outdoor sources of LAN estimated using low-dynamic range DMSP data had insufficient variability across urban neighborhoods to evaluate. While high-dynamic range DMSP offered much better variability, it was not significantly associated with urinary aMT6s.
Conclusions
Future health studies should utilize the high-dynamic range DMSP data and should consider other potential sources of circadian disruption associated with living in lower SES neighborhoods.
doi:10.1186/1476-072X-12-39
PMCID: PMC3766028  PMID: 24127816
Circadian disruption; Light at night; Melatonin; aMT6s; Socioeconomic status; Women
7.  Determinants and Within-Person Variability of Urinary Cadmium Concentrations among Women in Northern California 
Environmental Health Perspectives  2013;121(6):643-649.
Background: Cadmium (Cd) is a toxic metal associated with increased morbidity and mortality. Urinary Cd (U-Cd) concentration is considered a biomarker of long-term exposure.
Objectives: Our objectives were to evaluate the within-person correlation among repeat samples and to identify predictors of U-Cd concentrations.
Methods: U-Cd concentrations (micrograms per liter) were measured in 24-hr urine samples collected from 296 women enrolled in the California Teachers Study in 2000 and a second 24-hr sample collected 3–9 months later from 141 of the participants. Lifestyle and sociodemographic characteristics were obtained via questionnaires. The Total Diet Study database was used to quantify dietary cadmium intake based on a food frequency questionnaire. We estimated environmental cadmium emissions near participants’ residences using a geographic information system.
Results: The geometric mean U-Cd concentration was 0.27 µg/L and the range was 0.1–3.6 µg/L. The intraclass correlation among repeat samples from an individual was 0.50. The use of a single 24-hr urine specimen to characterize Cd exposure in a case–control study would result in an observed odds ratio of 1.4 for a true odds ratio of 2.0. U-Cd concentration increased with creatinine, age, and lifetime pack-years of smoking among ever smokers or lifetime intensity-years of passive smoking among nonsmokers, whereas it decreased with greater alcohol consumption and number of previous pregnancies. These factors explained 42–44% of the variability in U-Cd concentrations.
Conclusion: U-Cd levels varied with several individual characteristics, and a single measurement of U-Cd in a 24-hr sample did not accurately reflect medium- to long-term body burden.
doi:10.1289/ehp.1205524
PMCID: PMC3672909  PMID: 23552363
cadmium; biomarkers; diet; exposure science; GIS
8.  The Association Between Neighborhood Characteristics and Body Size and Physical Activity in the California Teachers Study Cohort 
American journal of public health  2011;102(4):689-697.
Objectives
We considered interactions between physical activity and body mass index (BMI) and neighborhood factors.
Methods
We used recursive partitioning to identify predictors of low recreational physical activity (<2.5 hours/week) and overweight and obesity (BMI≥25.0 kg/m2) among 118 315 women in the California Teachers Study. Neighborhood characteristics were based on 2000 US Census data and Reference US business listings.
Results
Low physical activity and being overweight or obese were associated with individual sociodemographic characteristics, including race/ethnicity and age. Among White women aged 36 to 75 years, living in neighborhoods with more household crowding was associated with a higher probability of low physical activity (54% vs 45% to 51%). In less crowded neighborhoods where more people worked outside the home, the existence of fewer neighborhood amenities was associated with a higher probability of low physical activity (51% vs 46%). Among non–African American middle-aged women, living in neighborhoods with a lower socioeconomic status was associated with a higher probability of being overweight or obese (46% to 59% vs 38% in high–socioeconomic status neighborhoods).
Conclusions
Associations between physical activity, overweight and obesity, and the built environment varied by sociodemographic characteristics in this educated population.
doi:10.2105/AJPH.2011.300150
PMCID: PMC3410673  PMID: 21852626
9.  Long-Term Exposure to Air Pollution and Cardiorespiratory Disease in the California Teachers Study Cohort 
Rationale: Several studies have linked long-term exposure to particulate air pollution with increased cardiopulmonary mortality; only two have also examined incident circulatory disease.
Objectives: To examine associations of individualized long-term exposures to particulate and gaseous air pollution with incident myocardial infarction and stroke, as well as all-cause and cause-specific mortality.
Methods: We estimated long-term residential air pollution exposure for more than 100,000 participants in the California Teachers Study, a prospective cohort of female public school professionals. We linked geocoded residential addresses with inverse distance-weighted monthly pollutant surfaces for two measures of particulate matter and for several gaseous pollutants. We examined associations between exposure to these pollutants and risks of incident myocardial infarction and stroke, and of all-cause and cause-specific mortality, using Cox proportional hazards models.
Measurements and Main Results: We found elevated hazard ratios linking long-term exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), scaled to an increment of 10 μg/m3 with mortality from ischemic heart disease (IHD) (1.20; 95% confidence interval [CI], 1.02–1.41) and, particularly among postmenopausal women, incident stroke (1.19; 95% CI, 1.02–1.38). Long-term exposure to particulate matter less than 10 μm in aerodynamic diameter (PM10) was associated with elevated risks for IHD mortality (1.06; 95% CI, 0.99–1.14) and incident stroke (1.06; 95% CI, 1.00–1.13), while exposure to nitrogen oxides was associated with elevated risks for IHD and all cardiovascular mortality.
Conclusions: This study provides evidence linking long-term exposure to PM2.5 and PM10 with increased risks of incident stroke as well as IHD mortality; exposure to nitrogen oxides was also related to death from cardiovascular diseases.
doi:10.1164/rccm.201012-2082OC
PMCID: PMC3208653  PMID: 21700913
particulate matter; cardiovascular diseases; air pollutants; epidemiology
10.  Birth Anomalies and Obstetric History as Risks for Childhood Tumors of the Central Nervous System 
Pediatrics  2011;128(3):e652-e657.
OBJECTIVE:
The causes of childhood central nervous system (CNS) tumors are largely unknown. Birth characteristics have been examined as possible risk factors for childhood CNS tumors, although the studies have been underpowered and inconclusive. We hypothesized that birth anomalies and a mother's history of previous pregnancy losses, as a proxy for genetic defects, increase the risk for CNS tumors.
METHODS:
From the California Cancer Registry, we identified 3733 patients aged 0 to 14 years with CNS tumors, diagnosed from 1988 through 2006 and linked to a California birth certificate. Four controls were matched to each patient. We calculated odds ratios (ORs) for the reported presence of a birth defect and for history of pregnancy losses by using logistic regression, adjusted for race, Hispanic ethnicity, maternal age, birth weight, and birth order.
RESULTS:
Offspring from mothers who had ≥2 fetal losses after 20 weeks' gestation had a threefold risk for CNS tumors (OR: 3.13 [95% confidence interval (CI): 1.32–7.41]) and a 14-fold risk for high-grade glioma (OR: 14.28 [95% CI: 1.56–130.65]). Birth defects increased risk for the CNS cancers medulloblastoma (OR: 1.70 [95% CI: 1.12–2.57]), primitive neuroectodermal tumor (OR: 3.64 [95% CI: 1.54–8.56]), and germ cell tumors (OR: 6.40 [95% CI: 2.09–19.56]).
CONCLUSIONS:
Multiple pregnancy losses after 20 weeks' gestation and birth defects increase the risk of a childhood CNS tumor. Previous pregnancy losses and birth defects may be surrogate markers for gene defects in developmental pathways that lead to CNS tumorigenesis.
doi:10.1542/peds.2010-3637
PMCID: PMC3164097  PMID: 21824884
childhood brain tumors; congenital anomalies; birth defects; central nervous system tumors
11.  Cigarette Smoking, Passive Smoking, and Non-Hodgkin Lymphoma Risk: Evidence From the California Teachers Study 
American Journal of Epidemiology  2011;174(5):563-573.
Epidemiologic studies conducted to date have shown evidence of a causal relation between smoking and non-Hodgkin lymphoma (NHL) risk. However, previous studies did not account for passive smoking exposure in the never-smoking reference group. The California Teachers Study collected information about lifetime smoking and household passive smoking exposure in 1995 and about lifetime exposure to passive smoking in 3 settings (household, workplace, and social settings) in 1997–1998. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2007. Compared with never smokers, ever smokers had a 1.11-fold (95% confidence interval (CI): 0.94, 1.30) higher NHL risk that increased to a 1.22-fold (95% CI: 0.95, 1.57) higher risk when women with household passive smoking were excluded from the reference category. Statistically significant dose responses were observed for lifetime cumulative smoking exposure (intensity and pack-years; both P ’s for trend = 0.02) when women with household passive smoking were excluded from the reference category. Among never smokers, NHL risk increased with increasing lifetime exposure to passive smoking (relative risk = 1.51 (95% CI: 1.03, 2.22) for >40 years vs. ≤5 years of passive smoking; P for trend = 0.03), particularly for follicular lymphoma (relative risk = 2.89 (95% CI: 1.23, 6.80); P for trend = 0.01). The present study provides evidence that smoking and passive smoking may influence NHL etiology, particularly for follicular lymphoma.
doi:10.1093/aje/kwr127
PMCID: PMC3202153  PMID: 21768403
cohort studies; lymphoma, non-Hodgkin; smoking; tobacco smoke pollution
12.  Hormonal Factors and the Risk of Papillary Thyroid Cancer in the California Teachers Study Cohort 
Background
Despite the increasing incidence of thyroid cancer, there is limited information on its etiology. The strikingly higher rates in young women, compared to men, suggest that sex steroid hormones may be involved in the development of this disease.
Methods
We investigated the effects of menstrual, reproductive, and other hormonal factors on papillary thyroid cancer risk in the prospective California Teachers Study (CTS) cohort. Among 117,646 women, 233 were diagnosed with invasive histologically-confirmed papillary thyroid cancer after cohort enrollment and before January 1, 2008. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models.
Results
Among younger women (age <45 years at baseline; approximately one-third of the cohort), but not older women, later age at menarche (age ≥14 years) was associated with increased risk (RR=1.88, 95% CI: 1.13–3.13; pinteraction by age=0.06). Risk was also increased among young women who had longer (>30 days) adolescent menstrual cycles (RR=1.78, 95% CI: 1.01–3.14) and whose last pregnancy had ended within five years of cohort enrollment (RR=2.21, 95% CI: 1.13–4.34). Among older women (age ≥45 years at baseline), ever use of estrogen-only therapy was associated with a statistically non-significant increase in risk (RR=1.69, 95% CI: 0.95–2.98).
Conclusions
The findings from this prospective analysis suggest that several factors related to delayed pubertal development and the transient effects of pregnancy may be particularly important in influencing risk in young women.
Impact
These results suggest the importance of future research into the role of progesterone and the estrogen-to-progesterone ratio.
doi:10.1158/1055-9965.EPI-11-0381
PMCID: PMC3288117  PMID: 21791618
papillary thyroid cancer; menstrual factors; reproductive factors; exogenous hormone use; epidemiology
13.  Birth order and Risk of Childhood Cancer: A Pooled Analysis from Five U.S. States 
The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case-control dataset. The subjects were drawn from population-based registries of cancers and births in California, Minnesota, New York, Texas, and Washington. We included 17,672 cases less than 15 years of age who were diagnosed from1980-2004 and 57,966 randomly selected controls born 1970-2004, excluding children with Down syndrome. We calculated odds ratios and 95% confidence intervals using logistic regression, adjusted for sex, birth year, maternal race, maternal age, multiple birth, gestational age, and birth weight. Overall, we found an inverse relationship between childhood cancer risk and birth order. For children in the fourth or higher birth order category compared to first-born children, the adjusted OR was 0.87 (95% CI: 0.81, 0.93) for all cancers combined. When we examined risks by cancer type, a decreasing risk with increasing birth order was seen in the central nervous system (CNS) tumors, neuroblastoma, bilateral retinoblastoma, Wilms tumor, and rhabdomyosarcoma. We observed increased risks with increasing birth order for acute myeloid leukemia but a slight decrease in risk for acute lymphoid leukemia. These risk estimates were based on a very large sample size which allowed us to examine rare cancer types with greater statistical power than in most previous studies, however the biologic mechanisms remain to be elucidated.
doi:10.1002/ijc.25593
PMCID: PMC3008504  PMID: 20715170
birth order; case-control studies; child; epidemiology; neoplasms
14.  MENOPAUSAL HORMONE THERAPY DOES NOT INFLUENCE LUNG CANCER RISK: RESULTS FROM THE CALIFORNIA TEACHERS STUDY 
Background
Results from studies examining the association between hormone therapy (HT) and lung cancer risk disagree.
Methods
We examined the associations between HT use and lung cancer risk among 60,592 postmenopausal women enrolled in the prospective California Teachers Study cohort. Between 1995 and 2007, 727 women were diagnosed with lung cancer. Multivariable Cox proportional hazards regression models were fit using age as the time metric.
Results
No measure of HT use was associated with lung cancer risk (all p-values for trend≥0.4). In addition, no variations in risk by smoking status (never, ever, former, current), type of HT (E-alone, E+P use), type of menopause, or lung cancer histology were observed.
Conclusions
Our findings do not support an association between HT and lung cancer.
Impact
This large-scale, prospective study, which capitalizes on the detailed hormone use, smoking history, and type of menopause information available within this unique cohort, was unable to find any association between intake of HT and lung cancer risk.
doi:10.1158/1055-9965.EPI-10-1182
PMCID: PMC3065239  PMID: 21266521
15.  Survival following non-small cell lung cancer among Asian/Pacific Islander, Latina, and non-Hispanic White women who have never smoked 
BACKGROUND
Lung cancer is the leading cause of cancer death among US Asian/Pacific Islander (API) and Latina women, despite low smoking prevalence. This study examined survival patterns following non-small cell lung cancer in a population-based sample of lung cancer cases from the San Francisco Bay Area Lung Cancer Study (SFBALCS).
METHODS
Women diagnosed with lung cancer from 1998–2003 and 2005–2008 and identified through the Greater Bay Area Cancer Registry were telephone-screened for eligibility for the SFBALCS. The screener data were linked to the cancer registry data to determine follow-up. This analysis included 187 non-Hispanic White, 23 US-born Latina, 32 foreign-born Latina, 30 US-born API, and 190 foreign-born API never smokers diagnosed with lung cancer and followed through 2008.
RESULTS
All-cause survival was poorer among APIs (hazard ratio (HR) and 95% confidence interval (CI) = 1.7 (1.0–2.8) among US-born APIs; 1.2 (0.9–1.5) among foreign-born APIs), and Latinas (HR (95% CI) = 2.1 (1.2–3.6) among US-born Latinas; 1.4 (0.9–2.3) among foreign-born Latinas), relative to non-Hispanic Whites. These survival differences were not explained by differences in selected sociodemographic or clinical factors.
CONCLUSIONS
Further research should focus on factors such as cultural behaviors, access to or attitudes toward health care, and genetic variations, as possible explanations for these striking racial/ethnic differences.
IMPACT
Latina and API female never smokers diagnosed with lung cancer were up to two-times more likely to die than non-Hispanic Whites, highlighting the need for additional research to identify the underlying reasons for the disparities, as well as heightened clinical awareness.
doi:10.1158/1055-9965.EPI-10-0965
PMCID: PMC3070404  PMID: 21239685
lung cancer survival; Asian; Latina; Hispanic; never smokers; nativity
16.  Age-specific effects of hormone therapy use on overall mortality and ischemic heart disease mortality among women in the California Teachers Study 
Menopause (New York, N.y.)  2011;18(3):253-261.
Objective
Although the Women’s Health Initiative trial (WHI) suggested that menopausal hormone therapy (HT) does not reduce coronary heart disease mortality overall, subsequent results have suggested that there may be a benefit in younger women. The California Teachers Cohort Study (CTS) questionnaire and mortality data was used to examine whether age modified the association between HT and the relative risk of overall mortality and ischemic heart disease (IHD) deaths.
Methods
Participants from the CTS were 71,237 postmenopausal women (mean age = 63, range 36 to 94 years) followed prospectively for mortality and other outcomes from 1995–1996 through 2004.
Results
Age at baseline was a much more important modifier of HT effects than age at start of therapy. Risks for all-cause mortality (n=8,399) were lower for younger current HT users at baseline than for never users (for women ≤60 years: HR=0.54, 95% CI=0.46–0.62). These risk reductions greatly diminished, in a roughly linear fashion, with increasing baseline age (for women 85–94 years HR=0.94, 95% CI=0.81–1.10 for all-cause mortality). Similar results were seen for IHD deaths (n=1,464). No additional significant modifying effects of age at first use, duration of use, or formulation were apparent.
Conclusions
These results provide evidence that reduced risks of mortality associated with HT use are observed among younger users but not for older postmenopausal women even those starting therapy close to their time of menopause.
doi:10.1097/gme.0b013e3181f0839a
PMCID: PMC3253313  PMID: 20881652
Overall mortality; heart disease; menopausal hormone therapy; risk; survival; age
17.  Body size and the risk of ovarian cancer by hormone therapy use in the California Teachers Study cohort 
Cancer causes & control : CCC  2010;21(12):2241-2248.
Objective
To investigate whether obesity and hormone therapy (HT) are associated with ovarian cancer risk among women in the California Teachers Study cohort.
Methods
Of 56,091 women age ≥45 years, 277 developed epithelial ovarian cancer between 1995 and 2007. Multivariate Cox regression was performed.
Results
Among women who never used HT, greater adult weight gain, waist circumference and waist-to-height ratio, but not adult BMI, increased risk of ovarian cancer. Compared to women who never used HT and had a stable adult weight, risk of ovarian cancer was increased in women who gained ≥40 lb (relative risk (RR) 1.8, 95% confidence interval (CI): 1.0–3.0) or used HT for >5 years (RR 2.3 95% CI: 1.3–4.1). Having both exposures (RR 1.9, 95% CI: 0.99–3.5), however, did not increase risk more than having either alone. Results were similar for waist circumference and weight-to-height ratio; however, differences across HT groups were not statistically significant.
Conclusions
This study suggests that abdominal adiposity and weight gain, but not overall obesity, increase ovarian cancer risk and that there may be a threshold level beyond which additional hormones, whether exogenous or endogenous, do not result in additional elevation in risk. However, large pooled analyses are needed to confirm these findings.
doi:10.1007/s10552-010-9647-x
PMCID: PMC3120052  PMID: 20924664
Ovarian cancer; Obesity; Abdominal adiposity; Hormone therapy
18.  Body size and the risk of endometrial cancer by hormone therapy use in postmenopausal women in the California Teachers Study cohort 
Cancer causes & control : CCC  2010;21(9):1407-1416.
Objective
To investigate whether hormone therapy (HT) and obesity are associated with endometrial cancer risk among postmenopausal women in the California Teachers Study cohort.
Methods
Of 28,418 postmenopausal women, 395 developed type 1 endometrial cancer between 1995 and 2006. Multivariate Cox regression was performed to estimate relative risks (RR), stratified by HT use (never used, ever estrogen-alone (ET), or exclusively estrogen-plus-progestin (EPT)).
Results
Among women who never used HT, overall and abdominal adiposity were associated with increased risk; when evaluated simultaneously, abdominal adiposity was more strongly associated (RR 2.2, 95% confidence interval (CI): 1.1–4.5 for waist ≥35 vs. <35 inches). Among women who ever used ET, risk was increased in women with BMI ≥25 kg/m2 (RR 1.6, 95% CI: 1.1–2.3 vs. <25 kg/m2). Neither overall nor abdominal obesity was associated with risk in women who exclusively used EPT (P-interaction<0.001 for BMI by HT use).
Conclusions
Among women who never used HT, risk was strongly positively related to obesity and may have been influenced more by abdominal than overall adiposity; however, due to small numbers, this latter finding requires replication. Among women who ever used ET, being overweight at baseline predicted higher risk, whereas use of EPT mitigated any effect of obesity.
doi:10.1007/s10552-010-9568-8
PMCID: PMC2925506  PMID: 20431936
endometrial cancer; obesity; abdominal adiposity; hormone therapy
19.  Determinants of Agricultural Pesticide Concentrations in Carpet Dust 
Environmental Health Perspectives  2011;119(7):970-976.
Background: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes.
Objective: We identified determinants of concentrations of agricultural pesticides in dust.
Methods: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California. We measured concentrations of seven pesticides used extensively in agriculture (carbaryl, chlorpyrifos, chlorthal-dimethyl, diazinon, iprodione, phosmet, and simazine). We estimated use of agricultural pesticides near residences from a statewide database alone and by linking the database with crop maps. We calculated the density of pesticide use within 500 and 1,250 m of residences for 180, 365, and 730 days before collection of dust and evaluated relationships between agricultural pesticide use estimates and pesticide concentrations in carpet dust.
Results: For five of the seven pesticides evaluated, residences with use of agricultural pesticides within 1,250 m during the previous 365 days had significantly higher concentrations of pesticides than did residences with no nearby use. The highest correlation with concentrations of pesticides was generally for use reported within 1,250 m of the residence and 730 days before sample collection. Regression models that also accounted for occupational and home use of pesticides explained only a modest amount of the variability in pesticide concentrations (4–28%).
Conclusions: Agricultural pesticide use near residences was a significant determinant of concentrations of pesticides in carpet dust for five of seven pesticides evaluated.
doi:10.1289/ehp.1002532
PMCID: PMC3222988  PMID: 21330232
agriculture; dust; exposure; GIS; pesticides
20.  Childhood cancer in relation to parental race and ethnicity: a five-state pooled analysis 
Cancer  2010;116(12):3045-3053.
Background
Children of different racial/ethnic backgrounds have varying risks of cancer. However, few studies have examined cancer occurrence in mixed ancestry children.
Methods
Population-based case-control study examining cancer among children age <15 years using linked cancer and birth-registry data from 5 U.S. states from 1978 to 2004. Data were available for 13,249 cancer cases and 36,996 controls selected from birth records. Parental race/ethnicity was determined from birth records. Logistic regression was used to examine the association of cancer with different racial/ethnic groups.
Results
Relative to Whites, Blacks had a 28% decreased risk of cancer (odds ratio (OR) 0.72, 95% CI 0.65–0.80), while both Asians and Hispanics had an approximate 15% decrease. Children of mixed White/Black ancestry also were at decreased risk (OR 0.71, 95% CI 0.56–0.90), but estimates for mixed White/Asian and White/Hispanic children did not differ from those of Whites. Relative to Whites: 1.) Black and mixed White/Black children had decreased ORs for acute lymphoblastic leukemia, (0.39, 95% CI 0.31–0.49) and (0.58, 95% CI 0.37–0.91), respectively; 2.) Asian and mixed White/Asian children had decreased ORs for brain tumors, (0.51, 95% CI 0.39–0.68) and (0.79, 95% CI 0.54–1.16), respectively; and 3.) Hispanic and mixed White/Hispanic children had decreased ORs for neuroblastoma (0.51, 95% CI 0.42–0.61) and (0.67, 95% CI 0.50–0.90), respectively.
Conclusion
The tendency of mixed ancestry children to have risks more similar to racial/ethnic minority children than the White majority group may help formulate etiologic studies designed to more directly study possible genetic and environmental differences.
doi:10.1002/cncr.25099
PMCID: PMC2903004  PMID: 20564410
child; ethnicity; neoplasms/epidemiology; race; risk factors
22.  Passive Smoking and Risk of Breast Cancer in the California Teachers Study*†‡ 
Background
Although recent reviews have suggested active smoking to be a risk factor for breast cancer, the association with passive smoke exposure remains controversial. This risk association was explored in a large prospective study of women, the California Teachers Study.
Methods
Detailed lifetime information on passive smoke exposure by setting (home, work, or social) and by age of exposure were collected in 1997 from 57,523 women who were lifetime nonsmokers and had no history of breast cancer. In the ensuing decade, a total of 1,754 women were diagnosed with invasive breast cancer. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) associated with several lifetime passive smoke exposure metrics.
Results
For all breast cancer, measures of higher lifetime passive smoking intensity and duration were associated with non-statistically significant HRs of 1.11 to 1.14. For postmenopausal women, HRs for lifetime low, medium and high cumulative exposure were 1.17 (95%CI 0.91, 1.49), 1.19 (95%CI 0.93, 1.53), and 1.26 (95% CI 0.99, 1.60). For women exposed in adulthood (age ≥20) risk was elevated at the highest level of cumulative exposure (HR=1.18, 95% CI 1.00, 1.40), primarily among postmenopausal women (HR=1.25, 95% CI 1.01, 1.56). A statistically significant dose response was detected when analysis was restricted to women with moderate to high levels of passive smoke exposure.
Conclusion
These results suggest that cumulative exposures to high levels of side stream smoke may increase breast cancer risk among postmenopausal women who themselves have never smoked tobacco products.
doi:10.1158/1055-9965.EPI-09-0936
PMCID: PMC2908531  PMID: 19959687
passive smoking; tobacco; breast cancer; cohort study; women
23.  Factors Associated with Residential Mobility in Children with Leukemia: Implications for Assigning Exposures 
Annals of epidemiology  2009;19(11):834-840.
Purpose
In epidemiologic studies, neighborhood characteristics are often assigned to individuals based on a single residence despite the fact that people frequently move and, for most cancer outcomes, the relevant time-window of exposure is not known. The authors evaluated residential mobility patterns for a population-based series of childhood leukemia cases enrolled in the Northern California Childhood Leukemia Study.
Methods
Complete residential history from one year prior to birth to date of diagnosis was obtained for 380 cases diagnosed between 1995 and 2002. All residences were assigned U.S. Census block group designations using a geographic information system.
Results
Overall, two-thirds (65.8%) of children had moved between birth and diagnosis, and a third (34.5%) moved during the first year of life. Approximately 25% of the mothers had moved during the year before the child's birth. Multivariable analysis indicated greater residential mobility to be associated with older age of the child at diagnosis, younger age of the mother at child's birth, and lower household income. Among those who had moved, residential urban/rural status for birth and diagnosis residences changed for about 20% of subjects, and neighborhood SES for 35%.
Conclusions
These results suggest that neighborhood attribute estimates in health studies should account for patterns of residential mobility. Estimates based on a single residential location at a single point in time may lead to different inferences.
doi:10.1016/j.annepidem.2009.03.001
PMCID: PMC2761989  PMID: 19364662
Childhood leukemia; Epidemiology; Exposure classification; Residential mobility; Socioeconomic status
24.  Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study 
Introduction
Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival.
Methods
California Teachers Study cohort members provided information in 1995–1996 on long-term (high school through age 54 years) and recent (past 3 years) participation in moderate and strenuous recreational physical activities. The 3,539 women diagnosed with invasive breast cancer after cohort entry and through December 31, 2004, were followed through December 31, 2005. Of these, 460 women died, 221 from breast cancer. Moderate and strenuous physical activities were combined into low (≤0.50 hr/wk/yr of any activity), intermediate (0.51–3.0 hr/wk/yr of moderate or strenuous activity but no activity >3.0 hr/wk/yr) or high activity (>3.0 hr/wk/yr of either activity type). Multivariable relative risks (RR) and 95% confidence intervals (CI) for mortality were estimated using Cox proportional hazards methods, adjusting for race/ethnicity, estrogen receptor status, disease stage, and baseline information on comorbidities, body mass index, and caloric intake.
Results
Women with high or intermediate levels of long-term physical activity had lower risk of breast cancer death (RR=0.53, 95% CI=0.35–0.80; and RR=0.65, 95% CI=0.45–0.93, respectively) than women with low activity levels. These associations were consistent across estrogen receptor status and disease stage, but confined to overweight women. Deaths due to causes other than breast cancer were related only to recent activity.
Conclusions
Consistent long-term participation in physical activity before breast cancer diagnosis may lower risk of breast cancer death, providing further justification for public health strategies to increase physical activity throughout the lifespan.
doi:10.1158/1055-9965.EPI-09-0538
PMCID: PMC2783945  PMID: 19843680
25.  Residential Proximity to Agricultural Pesticide Applications and Childhood Acute Lymphoblastic Leukemia 
Environmental research  2009;109(7):891-899.
Ambient exposure from residential proximity to applications of agricultural pesticides may contribute to the risk of childhood acute lymphoblastic leukemia (ALL). Using residential histories collected from the families of 213 ALL cases and 268 matched controls enrolled in the Northern California Childhood Leukemia Study, the authors assessed residential proximity within a half-mile (804.5 meters) of pesticide applications by linking address histories with reports of agricultural pesticide use. Proximity was ascertained during different time windows of exposure, including the first year of life and the child’s lifetime through the date of diagnosis for cases or reference for controls. Agricultural pesticides were categorized a priori into groups based on similarities in toxicological effects, physicochemical properties, and target pests or uses. The effects of moderate and high exposure for each group of pesticides were estimated using conditional logistic regression. Elevated ALL risk was associated with lifetime moderate exposure, but not high exposure, to certain physicochemical categories of pesticides, including organophosphates, cholorinated phenols, and triazines, and with pesticides classified as insecticides or fumigants. A similar pattern was also observed for several toxicological groups of pesticides. These findings suggest future directions for the identification of specific pesticides that may play a role in the etiology of childhood leukemia.
doi:10.1016/j.envres.2009.07.014
PMCID: PMC2748130  PMID: 19700145
Agricultural pesticides; cancer; childhood leukemia; environmental exposure; geographic information systems

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