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1.  A genome-wide association study of Hodgkin Lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21, and 10p14 (GATA3) 
Nature genetics  2010;42(12):1126-1130.
To identify predisposition loci for classical Hodgkin Lymphoma (cHL) we conducted a genome-wide association study of 589 cHL cases and 5,199 controls with validation in 4 independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL; odds ratio [OR]=1.22, Pcombined=1.91×10−8), 8q24.21 (rs2019960, PVT1; OR=1.33, Pcombined=1.26×10−13) and 10p14 (rs501764, GATA3; OR=1.25, Pcombined=7.05×10−8). Furthermore, we confirmed the role of the MHC in disease etiology by revealing a strong HLA association (rs6903608; OR=1.70, Pcombined=2.84×10−50). These data provide new insight into the pathogenesis of cHL.
PMCID: PMC4268499  PMID: 21037568
2.  How Do Social Factors Explain Outcomes in Non–Small-Cell Lung Cancer Among Hispanics in California? Explaining the Hispanic Paradox 
Journal of Clinical Oncology  2013;31(28):3572-3578.
Hispanics in the United States have lower age-adjusted mortality resulting from non–small-cell lung cancer (NSCLC) compared with non-Hispanic whites (NHWs). The purpose of this study was to evaluate individual, clinical, and neighborhood factors in survival among Hispanics with NSCLC.
Patients and Methods
We performed a retrospective analysis of NHWs and Hispanics with NSCLC between 1998 and 2007 in the California Cancer Registry (follow-up to December 2009). Kaplan-Meier curves depict survival by nativity for Hispanics with NSCLC. Cox proportional hazards models estimated hazard of mortality by race with adjustment for individual (age, sex, marital status), clinical (histologic grade, surgery, irradiation, chemotherapy), and neighborhood factors (neighborhood socioeconomic status, ethnic enclave).
We included 14,280 Hispanic patients with NSCLC. Foreign-born Hispanics had 15% decreased risk of disease-specific mortality resulting from NSCLC compared with NHWs (hazard ratio [HR], 0.85; 95% CI, 0.83 to 0.88) after adjustment for individual, clinical, and neighborhood factors. After adjustment for individual factors, compared with US-born Hispanics, foreign-born Hispanics had 10% decreased risk of disease-specific mortality (HR, 0.90; 95% CI, 0.87 to 0.96). Clinical and neighborhood factors slightly moderated the survival benefit for foreign-born patients. A modestly more pronounced survival advantage was seen for foreign-born Hispanics living in low socioeconomic and high Hispanic enclave neighborhoods as compared with US-born Hispanics (HR, 0.86; 95% CI, 0.81 to 0.90).
Foreign-born Hispanics with NSCLC have a decreased risk of disease-specific mortality compared with NHWs and US-born Hispanics with NSCLC. Neighborhood factors slightly moderate this survival advantage. This survival advantage is slightly more pronounced in lower socioeconomic and higher Hispanic enclave neighborhoods.
PMCID: PMC3782149  PMID: 23960183
3.  A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer 
European Journal of Epidemiology  2014;29(10):667-723.
To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case–control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case–control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.
Electronic supplementary material
The online version of this article (doi:10.1007/s10654-014-9931-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4197347  PMID: 25064616
Prostate cancer; TCDD; Dioxin; Agent Orange; Veterans; Epidemiology
4.  Anthropometric, behavioral, and female reproductive factors and risk of multiple myeloma: a pooled analysis 
Cancer causes & control : CCC  2013;24(7):1279-1289.
Risk of developing multiple myeloma (MM) rises with age and is greater among men and blacks than among women and whites, respectively, and possibly increased among obese persons. Other risk factors remain poorly understood. By pooling data from two complementary epidemiologic studies, we assessed whether obesity, smoking, or alcohol consumption alters MM risk and whether female reproductive history might explain the lower occurrence of MM in females than males.
The Los Angeles County MM Case-Control Study (1985-92) included 278 incident cases and 278 controls, matched on age, sex, race, and neighborhood of residence at case’s diagnosis. We estimated MM risk using conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). In the prospective California Teachers Study (CTS), 152 women were diagnosed with incident MM between 1995-2009; we calculated hazard ratios using Cox proportional hazards analysis. Data from the two studies were pooled using a stratified, nested case-control sampling scheme (10:1 match) for the CTS; conditional logistic regression among 430 cases and 1,798 matched controls was conducted.
Obesity and smoking were not associated with MM risk in the individual or combined studies. Alcohol consumption was associated with decreased MM risk among whites only (pooled OR=0.66, 95% CI=0.49-0.90) for ever vs. never drinking). Higher gravidity and parity were associated with increased MM risk, with pooled ORs of 1.38 (95% CI=1.01-1.90) for ≥3 versus 1-2 pregnancies and 1.50 (95% CI=1.09-2.06) for ≥3 versus 1-2 live births.
Female reproductive history may modestly alter MM risk, but appears unlikely to explain the sex disparity in incidence. Further investigation in consortial efforts is warranted.
PMCID: PMC3684420  PMID: 23568533
multiple myeloma; women; reproductive; modifiable; risk factors; association; pooling; case-control; cohort; epidemiology
5.  Subtype of Dietary Fat in Relation to Risk of Hodgkin Lymphoma: A Population-based Case-Control Study in Connecticut and Massachusetts 
Cancer causes & control : CCC  2013;24(3):485-494.
Few epidemiological studies have examined the relationship between dietary fat, which may affect immune function, and risk of Hodgkin lymphoma (HL). The aim of this study was to test the hypothesis that high dietary intake of fat and specific subtypes of fat is associated with the risk of HL among 486 HL cases and 630 population-based controls recruited between 1997–2000 in Connecticut and Massachusetts. Unconditional logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CIs) stratified by age and gender. Among younger adults, HL risk was significantly and positively associated with higher intake of saturated fat (ORs for increasing quartiles= 1.3, 1.8, and 2.1; p trend = 0.04), and negatively associated with higher intake of monounsaturated fat (ORs for increasing quartiles= 0.5, 0.5, and 0.4; p trend = 0.03), after adjustment for potential confounders including lifestyle and other dietary factors. The associations with saturated fat (ORs for increasing quartile = 2.4, 3.2, and 4.4; p trend < 0.01) and monounsaturated fat (ORs for increasing quartile= 0.3, 0.6, and 0.3; p trend = 0.04) were most apparent in younger women, whereas there was no significant association between intake of total fat or any type of fat and risk of HL in older females or younger or older males. These findings show that the associations between dietary fat and risk of HL may vary by gender and age, and require confirmation in other populations.
PMCID: PMC4044911  PMID: 23314676
Hodgkin lymphoma; dietary fat; saturated fat; monounsaturated fat
6.  Body Size and Risk of Hodgkin Lymphoma by Age and Gender: A Population-based Case-Control Study in Connecticut and Massachusetts 
Cancer causes & control : CCC  2012;24(2):287-295.
Descriptive studies have indicated a rising trend in Hodgkin lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender.
A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997–2000. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs).
Among younger women < 35 years old, being overweight (25–29.9 kg/m2) vs. normal weight (18.5–24.9 kg/m2) was significantly associated with an increased risk of HL (OR = 2.1, 95% CI = 1.1–4.0). The risk increased with increasing weight and BMI (P trends < 0.01). Among women ≥ 35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (P trends < 0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males.
These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.
PMCID: PMC3557669  PMID: 23208661
Hodgkin lymphoma; body size; body mass index; height; weight
7.  Genome-wide Association Study Identifies Multiple Risk Loci for Chronic Lymphocytic Leukemia 
Berndt, Sonja I. | Skibola, Christine F. | Joseph, Vijai | Camp, Nicola J. | Nieters, Alexandra | Wang, Zhaoming | Cozen, Wendy | Monnereau, Alain | Wang, Sophia S. | Kelly, Rachel S. | Lan, Qing | Teras, Lauren R. | Chatterjee, Nilanjan | Chung, Charles C. | Yeager, Meredith | Brooks-Wilson, Angela R. | Hartge, Patricia | Purdue, Mark P. | Birmann, Brenda M. | Armstrong, Bruce K. | Cocco, Pierluigi | Zhang, Yawei | Severi, Gianluca | Zeleniuch-Jacquotte, Anne | Lawrence, Charles | Burdette, Laurie | Yuenger, Jeffrey | Hutchinson, Amy | Jacobs, Kevin B. | Call, Timothy G. | Shanafelt, Tait D. | Novak, Anne J. | Kay, Neil E. | Liebow, Mark | Wang, Alice H. | Smedby, Karin E | Adami, Hans-Olov | Melbye, Mads | Glimelius, Bengt | Chang, Ellen T. | Glenn, Martha | Curtin, Karen | Cannon-Albright, Lisa A. | Jones, Brandt | Diver, W. Ryan | Link, Brian K. | Weiner, George J. | Conde, Lucia | Bracci, Paige M. | Riby, Jacques | Holly, Elizabeth A. | Smith, Martyn T. | Jackson, Rebecca D. | Tinker, Lesley F. | Benavente, Yolanda | Becker, Nikolaus | Boffetta, Paolo | Brennan, Paul | Foretova, Lenka | Maynadie, Marc | McKay, James | Staines, Anthony | Rabe, Kari G. | Achenbach, Sara J. | Vachon, Celine M. | Goldin, Lynn R | Strom, Sara S. | Lanasa, Mark C. | Spector, Logan G. | Leis, Jose F. | Cunningham, Julie M. | Weinberg, J. Brice | Morrison, Vicki A. | Caporaso, Neil E. | Norman, Aaron D. | Linet, Martha S. | De Roos, Anneclaire J. | Morton, Lindsay M. | Severson, Richard K. | Riboli, Elio | Vineis, Paolo | Kaaks, Rudolph | Trichopoulos, Dimitrios | Masala, Giovanna | Weiderpass, Elisabete | Chirlaque, María-Dolores | Vermeulen, Roel C H | Travis, Ruth C. | Giles, Graham G. | Albanes, Demetrius | Virtamo, Jarmo | Weinstein, Stephanie | Clavel, Jacqueline | Zheng, Tongzhang | Holford, Theodore R | Offit, Kenneth | Zelenetz, Andrew | Klein, Robert J. | Spinelli, John J. | Bertrand, Kimberly A. | Laden, Francine | Giovannucci, Edward | Kraft, Peter | Kricker, Anne | Turner, Jenny | Vajdic, Claire M. | Ennas, Maria Grazia | Ferri, Giovanni M. | Miligi, Lucia | Liang, Liming | Sampson, Joshua | Crouch, Simon | Park, Ju-hyun | North, Kari E. | Cox, Angela | Snowden, John A. | Wright, Josh | Carracedo, Angel | Lopez-Otin, Carlos | Bea, Silvia | Salaverria, Itziar | Martin, David | Campo, Elias | Fraumeni, Joseph F. | de Sanjose, Silvia | Hjalgrim, Henrik | Cerhan, James R. | Chanock, Stephen J. | Rothman, Nathaniel | Slager, Susan L.
Nature genetics  2013;45(8):868-876.
PMCID: PMC3729927  PMID: 23770605
8.  Cancer mortality and quantitative oil production in the Amazon region of Ecuador, 1990–2010 
Cancer Causes & Control  2013;25(1):59-72.
Controversy persists over whether cancer risk is increased in communities surrounding oil fields, especially in the Oriente region of Ecuador. This ecologic study uses quantitative exposure data, updated mortality data, and improved statistical methods to study the impact of oil exploration and production activities on cancer mortality rates in the Oriente.
Cancer mortality rates in the Oriente in 1990 through 2010 were compared between seven cantons with active oil exploration and production as of 1990 and thirteen cantons with little or no such activities. Poisson regression was used to estimate mortality rate ratios (RRs) adjusted for age and sex. In a two-stage analysis, canton-specific log-RRs were regressed against quantitative estimates of cumulative barrels of oil produced and well-years per canton, adjusting for canton-level demographic and socioeconomic factors.
Overall and site-specific cancer mortality rates were comparable between oil-producing and non-oil-producing cantons. For overall cancer mortality in males and females combined, the RR comparing oil-producing to non-oil-producing cantons was 0.85 [95 % confidence interval (CI) 0.72–1.00]. For leukemia mortality, the corresponding RR was 0.80 (95 % CI 0.57–1.13). Results also revealed no excess of mortality from acute non-lymphocytic, myeloid, or childhood leukemia. Standardized mortality ratios were consistent with RRs. Canton-specific RRs showed no pattern in relation to oil production volume or well-years.
Results from this first ecologic study to incorporate quantitative measures of oil exploration and production showed no association between the extent of these activities and cancer mortality, including from cancers associated with benzene exposure.
Electronic supplementary material
The online version of this article (doi:10.1007/s10552-013-0308-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3889987  PMID: 24293001
Cancer; Ecuador; Epidemiology; Leukemia; Mortality; Petroleum
9.  Treatment and Mortality in Men with Localized Prostate Cancer: A Population-Based Study in California 
To provide patients and physicians with population-based estimates of mortality from prostate cancer or other causes depending upon the primary treatment modality, stratified by patient age, tumor stage and grade.
We conducted a 10-year competing-risk analysis of 45,440 men diagnosed with clinically localized (T1 or T2) prostate cancer in California during 1995–1998. Information on patient characteristics, primary treatment and cause of death was obtained from the California Cancer Registry.
In this population-based cohort, the most common primary treatment was surgery (40.4%), followed by radiotherapy (29.1%), conservative management (20.8%), and androgen deprivation therapy (ADT) monotherapy (9.8%). Prostate cancer mortality differed significantly (p < 0.0001) across treatment groups among patients <80 years at diagnosis with moderately or poorly differentiated disease; the 10-year disease-specific mortality rates were generally highest for men treated with ADT monotherapy [range: 3.3% (95% CI=0.8–12.5%) to 53.8% (95% CI=34.4–72.2%)], intermediate for men treated with conservative management [range: 1.7% (95% CI=0.7–4.6%) to 30.0% (95% CI=16.2–48.8%] or radiotherapy [range: 3.2% (95% CI=1.8–5.5%) to 18.3% (95% CI=15.1–22.0%)], and lowest for men treated with surgery [range: 1.2% (95% CI=0.8–1.7%) to 11.0% (95% CI=8.4–14.2%)].
The cause-specific mortality estimates provided by this observational study can help patients and physicians better understand the expected long-term outcomes of localized prostate cancer given the initial treatment choice and practice patterns in the general population.
PMCID: PMC3758138  PMID: 23997838
Prostate cancer; treatment; mortality; cohort study; California Cancer Registry
10.  Nativity and papillary thyroid cancer incidence rates among Hispanic women in California 
Cancer  2011;118(1):216-222.
Overall, the incidence of papillary thyroid cancer in Hispanic women residing in the United States (US) is similar to that of non-Hispanic white women. However, little is known as to whether rates in Hispanic women vary by nativity, which may influence exposure to important risk factors.
Nativity-specific incidence rates among Hispanic women were calculated for papillary thyroid cancer using data from the California Cancer Registry (CCR) for the period 1988–2004. For the 35% of cases for whom birthplace information was not available from the CCR, nativity was statistically imputed based on age at Social Security number issuance. Population estimates were extracted based on US Census data. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were also estimated.
In young (age <55 years) Hispanic women, the incidence of papillary thyroid cancer among US-born (10.65 per 100,000) was significantly greater than that for foreign-born (6.67 per 100,000; IRR=1.60, 95% CI: 1.44–1.77). The opposite pattern was observed in older women. The age-specific patterns showed marked differences by nativity: among foreign-born, rates increased slowly until age 70 years, whereas, among US-born, incidence rates peaked during the reproductive years. Incidence rates increased over the study period in all subgroups.
Incidence rates of papillary thyroid cancer vary by nativity and age among Hispanic women residing in California. These patterns can provide insight for future etiologic investigations of modifiable risk factors for this increasingly common and understudied cancer.
PMCID: PMC3179782  PMID: 21692062
papillary thyroid cancer; incidence rates; nativity; Hispanic women; cancer surveillance
11.  Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses’ Health Study 
Cancer causes & control : CCC  2011;22(12):1731-1741.
Case-control studies suggest increased sun exposure reduces non-Hodgkin lymphoma (NHL) risk. Evidence from prospective cohort studies, however, is limited and inconsistent. We evaluated the association between ambient ultraviolet radiation (UV) exposure and NHL in a nationwide cohort of women, the Nurses’ Health Study (NHS).
Between 1976 and 2006, we identified 1064 incident NHL cases among 115,482 women in the prospective NHS. Exposures assessed included average annual UV-B flux based on residence at various times during life, vitamin D intake, and predicted plasma 25-hydroxyvitamin D levels. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of all NHL and histologic subtypes using Cox proportional hazards models.
NHL risk was increased for women residing in areas of high ambient UV radiation (UV-B flux >113 R-B count × 10−4) compared to those with lower exposure (<113), with positive linear trends at all time points. The multivariable-adjusted RR for high UV area at age 15 was 1.21 (95% CI: 1.00, 1.47; p-trend <0.01). There was no evidence of statistical heterogeneity by subtype, although power was limited for subtype analyses. We observed no association between vitamin D measures and risk of NHL overall or by subtype.
Our findings do not support the hypothesis of a protective effect of UV radiation exposure on NHL risk. We found no association between vitamin D and NHL risk.
PMCID: PMC3240999  PMID: 21987081
non-Hodgkin lymphoma; sunlight; ultraviolet radiation; vitamin D; epidemiology
12.  Nutrients and Genetic Variation Involved in One-Carbon Metabolism and Hodgkin Lymphoma Risk: A Population-based Case-Control Study 
American Journal of Epidemiology  2011;174(7):816-827.
Nutritional and genetic determinants of the one-carbon metabolism pathway have been related to risk of malignant lymphomas, but little is known about their associations with Hodgkin lymphoma risk specifically. The authors examined nutrient intake (folate, vitamin B2, vitamin B6, vitamin B12, methionine) and multivitamin use among 497 Hodgkin lymphoma patients and 638 population-based controls (Massachusetts and Connecticut, 1997–2000), and genetic variation (MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, SHMT1 1420C>T, TYMS 1494del6) and gene-diet interactions in a subset. Unconditional logistic regression was used to calculate multivariable odds ratios and 95% confidence intervals. Hodgkin lymphoma risk was not associated with total nutrient intake or intake from food alone (excluding supplements). Multivitamin use (odds ratio (OR) = 1.46, 95% CI: 1.09, 1.96), total vitamin B6 (ORquartile 4 vs. 1 = 1.62) (Ptrend = 0.03), and total vitamin B12 (ORquartile 4 vs. 1 = 1.75) (Ptrend = 0.02) intakes were positively associated with risk of Epstein-Barr virus-negative, but not -positive, disease. The 5 genetic variants were not significantly associated with Hodgkin lymphoma risk; no significant gene-diet interactions were observed after Bonferroni correction. Study findings do not support a strong role for nutrients and genetic variation in the one-carbon metabolism pathway in susceptibility to Hodgkin lymphoma. Associations between diet and risk of Epstein-Barr virus-negative disease require confirmation in other populations.
PMCID: PMC3203380  PMID: 21810727
case-control studies; diet; folic acid; Hodgkin disease; vitamins
13.  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.
PMCID: PMC3208653  PMID: 21700913
particulate matter; cardiovascular diseases; air pollutants; epidemiology
14.  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.
PMCID: PMC3202153  PMID: 21768403
cohort studies; lymphoma, non-Hodgkin; smoking; tobacco smoke pollution
15.  Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study 
We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and stratified Cox proportional hazards models were fit to estimate relative risks (RR) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95%CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95%CI=0.83-1.33) overall, or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95%CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.
PMCID: PMC3258672  PMID: 20957632
non-Hodgkin lymphoma; oral contraceptives; menopausal hormonal therapy; hysterectomy; bilateral oophorectomy
16.  Lymphoid malignancies in US Asians: incidence rate differences by birthplace and acculturation 
Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHLs), Hodgkin lymphoma (HL) and multiple myeloma (MM), occur at much lower rates in Asians than other racial/ethnic groups in the United States (US). It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status.
We obtained data regarding all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from US Census data.
While incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than US-born Asians, with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower-SES neighborhoods than those living elsewhere. Conclusions: These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL.
Studying specific lymphoid malignancies in US Asians may provide valuable insight towards understanding their environmental causes.
PMCID: PMC3111874  PMID: 21493873
lymphoid malignancies; Asians; immigration; environmental causes
17.  Survival following non-small cell lung cancer among Asian/Pacific Islander, Latina, and non-Hispanic White women who have never smoked 
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).
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.
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.
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.
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.
PMCID: PMC3070404  PMID: 21239685
lung cancer survival; Asian; Latina; Hispanic; never smokers; nativity
18.  Papillary thyroid cancer incidence rates vary significantly by birthplace in Asian American women 
Cancer causes & control : CCC  2011;22(3):479-485.
To investigate how birthplace influences the incidence of papillary thyroid cancer among Asian American women.
Birthplace- and ethnic-specific age-adjusted and age-specific incidence rates were calculated using data from the California Cancer Registry for the period 1988–2004. Birthplace was statistically imputed for 30% of cases using a validated imputation method based on age at Social Security number issuance. Population estimates were obtained from the US Census. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated for foreign-born vs. US-born women.
Age-adjusted incidence rates of papillary thyroid cancer among Filipina (13.7 per 100,000) and Vietnamese (12.7) women were more than double those of Japanese women (6.2). US-born Chinese (IRR=0.48, 95% CI: 0.40–0.59) and Filipina women (IRR=0.74, 95% CI: 0.58–0.96) had significantly higher rates than those who were foreign-born; the opposite was observed for Japanese women (IRR=1.55, 95% CI: 1.17–2.08). The age-specific patterns among all foreign-born Asian women and US-born Japanese women showed a slow steady increase in incidence until age 70. However, among US-born Asian women (except Japanese), substantially elevated incidence rates during the reproductive and menopausal years were evident.
Ethnic- and birthplace-variation in papillary thyroid cancer incidence can provide insight into the etiology of this increasingly common and understudied cancer.
PMCID: PMC3291661  PMID: 21207130
papillary thyroid cancer; incidence rates; birthplace; Asian American women; cancer surveillance
19.  Dietary phytocompounds and risk of lymphoid malignancies in the California Teachers Study cohort 
Cancer causes & control : CCC  2010;22(2):237-249.
We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women.
Between 1995-1996 and December 31, 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time-scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies.
Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ≥12.1 vs. <2.7 mcM/day=0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ≥2.2 vs. <0.9 μM Trolox equiv/g/day=0.68, 95% CI: 0.42-1.10; ptrend=0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds.
Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease risk of selected subtypes.
PMCID: PMC3074494  PMID: 21107674
lymphoma; diet; isothiocyanates; antioxidants; cohort studies
20.  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.
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.
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.
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.
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.
PMCID: PMC3253313  PMID: 20881652
Overall mortality; heart disease; menopausal hormone therapy; risk; survival; age
21.  Alcohol Consumption Over Time and Risk of Lymphoid Malignancies in the California Teachers Study Cohort 
American Journal of Epidemiology  2010;172(12):1373-1383.
Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995–1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18–22 years, at ages 30–35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.
PMCID: PMC3105275  PMID: 20952595
alcohol drinking; cohort studies; lymphoma, non-Hodgkin; multiple myeloma
22.  Disparities in liver cancer incidence by nativity, acculturation, and socioeconomic status in California Hispanics and Asians 
Asians and Hispanics have the highest incidence rates of liver cancer in the US, but little is known about how incidence patterns in these largely immigrant populations vary by nativity, acculturation, and socioeconomic status (SES). Such variations can identify high-priority subgroups for prevention and monitoring.
Incidence rates and rate ratios (IRRs) by nativity among 5,400 Hispanics and 5,809 Asians diagnosed with liver cancer in 1988–2004 were calculated in the California Cancer Registry. Neighborhood ethnic enclave status and SES were classified using 2000 US Census data for cases diagnosed in 1998–2002.
Foreign-born Hispanic males had significantly lower liver cancer incidence rates than US-born Hispanic males in 1988–2004 (e.g., IRR=0.54, 95% confidence interval [CI]=0.50–0.59), whereas foreign-born Hispanic females had significantly higher rates in 1988–1996 (IRR=1.42, 95% CI=1.18–1.71), but not 1997–2004. Foreign-born Asian males and females had up to 5-fold higher rates than the US-born. Among Hispanic females, incidence rates were elevated by 21% in higher-enclave versus lower-enclave neighborhoods, and by 24% in lower- versus higher-SES neighborhoods. Among Asian males, incidence rates were elevated by 23% in higher-enclave neighborhoods and by 21% in lower-SES neighborhoods. In both racial/ethnic populations, males and females in higher-enclave, lower-SES neighborhoods had higher incidence rates.
Nativity, residential enclave status, and neighborhood SES characterize Hispanics and Asians with significantly unequal incidence rates of liver cancer, implicating behavioral or environmental risk factors and revealing opportunities for prevention.
Liver cancer control efforts should especially target foreign-born Asians, US-born Hispanic men, and residents of lower-SES ethnic enclaves.
PMCID: PMC3005535  PMID: 20940276
23.  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.
To investigate whether obesity and hormone therapy (HT) are associated with ovarian cancer risk among women in the California Teachers Study cohort.
Of 56,091 women age ≥45 years, 277 developed epithelial ovarian cancer between 1995 and 2007. Multivariate Cox regression was performed.
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.
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.
PMCID: PMC3120052  PMID: 20924664
Ovarian cancer; Obesity; Abdominal adiposity; Hormone therapy
24.  Past recreational physical activity, body size, and all-cause mortality following breast cancer diagnosis: results from the Breast Cancer Family Registry 
Few studies have considered the joint association of body mass index (BMI) and physical activity, two modifiable factors, with all-cause mortality after breast cancer diagnosis. Women diagnosed with invasive breast cancer (n=4,153) between 1991 and 2000 were enrolled in the Breast Cancer Family Registry through population-based sampling in Northern California, USA; Ontario, Canada; and Melbourne and Sydney, Australia. During a median follow-up of 7.8 years, 725 deaths occurred. Baseline questionnaires assessed moderate and vigorous recreational physical activity and BMI prior to diagnosis. Associations with all-cause mortality were assessed using Cox proportional hazards regression, adjusting for established prognostic factors. Compared with no physical activity, any recreational activity during the three years prior to diagnosis was associated with a 34% lower risk of death (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.51-0.85) for women with estrogen receptor (ER)-positive tumors, but not those with ER-negative tumors; this association did not appear to differ by race/ethnicity or BMI. Lifetime physical activity was not associated with all-cause mortality. BMI was positively associated with all-cause mortality for women diagnosed at age ≥50 years with ER-positive tumors (compared with normal-weight women, HR for overweight = 1.39, 95% CI: 0.90-2.15; HR for obese = 1.77, 95% CI: 1.11-2.82). BMI associations did not appear to differ by race/ethnicity. Our findings suggest that physical activity and BMI exert independent effects on overall mortality after breast cancer.
PMCID: PMC2920352  PMID: 20140702
breast cancer; physical activity; body mass index; obesity; mortality
25.  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.
To investigate whether hormone therapy (HT) and obesity are associated with endometrial cancer risk among postmenopausal women in the California Teachers Study cohort.
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)).
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).
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.
PMCID: PMC2925506  PMID: 20431936
endometrial cancer; obesity; abdominal adiposity; hormone therapy

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