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1.  A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and immunological health conditions in humans 
Critical Reviews in Toxicology  2016;46(4):279-331.
Whether perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS), two widely used and biopersistent synthetic chemicals, are immunotoxic in humans is unclear. Accordingly, this article systematically and critically reviews the epidemiologic evidence on the association between exposure to PFOA and PFOS and various immune-related health conditions in humans. Twenty-four epidemiologic studies have reported associations of PFOA and/or PFOS with immune-related health conditions, including ten studies of immune biomarker levels or gene expression patterns, ten studies of atopic or allergic disorders, five studies of infectious diseases, four studies of vaccine responses, and five studies of chronic inflammatory or autoimmune conditions (with several studies evaluating multiple endpoints). Asthma, the most commonly studied condition, was evaluated in seven studies. With few, often methodologically limited studies of any particular health condition, generally inconsistent results, and an inability to exclude confounding, bias, or chance as an explanation for observed associations, the available epidemiologic evidence is insufficient to reach a conclusion about a causal relationship between exposure to PFOA and PFOS and any immune-related health condition in humans. When interpreting such studies, an immunodeficiency should not be presumed to exist when there is no evidence of a clinical abnormality. Large, prospective studies with repeated exposure assessment in independent populations are needed to confirm some suggestive associations with certain endpoints.
PMCID: PMC4819831  PMID: 26761418
Asthma; autoimmune diseases; CAS No. 335-67-1; CAS No. 1763-23-1; epidemiology; hypersensitivity; immune system;  immunization; immunological factors; infection; perfluoroalkyl substances; polyfluoroalkyl substances
2.  Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia 
Berndt, Sonja I. | Camp, Nicola J. | Skibola, Christine F. | Vijai, Joseph | Wang, Zhaoming | Gu, Jian | Nieters, Alexandra | Kelly, Rachel S. | Smedby, Karin E. | Monnereau, Alain | Cozen, Wendy | Cox, Angela | Wang, Sophia S. | Lan, Qing | Teras, Lauren R. | Machado, Moara | Yeager, Meredith | Brooks-Wilson, Angela R. | Hartge, Patricia | Purdue, Mark P. | Birmann, Brenda M. | Vajdic, Claire M. | Cocco, Pierluigi | Zhang, Yawei | Giles, Graham G. | Zeleniuch-Jacquotte, Anne | Lawrence, Charles | Montalvan, Rebecca | Burdett, Laurie | Hutchinson, Amy | Ye, Yuanqing | Call, Timothy G. | Shanafelt, Tait D. | Novak, Anne J. | Kay, Neil E. | Liebow, Mark | Cunningham, Julie M. | Allmer, Cristine | Hjalgrim, Henrik | Adami, Hans-Olov | Melbye, Mads | Glimelius, Bengt | Chang, Ellen T. | Glenn, Martha | Curtin, Karen | Cannon-Albright, Lisa A. | Diver, W Ryan | Link, Brian K. | Weiner, George J. | Conde, Lucia | Bracci, Paige M. | Riby, Jacques | Arnett, Donna K. | Zhi, Degui | Leach, Justin M. | Holly, Elizabeth A. | Jackson, Rebecca D. | Tinker, Lesley F. | Benavente, Yolanda | Sala, Núria | Casabonne, Delphine | Becker, Nikolaus | Boffetta, Paolo | Brennan, Paul | Foretova, Lenka | Maynadie, Marc | McKay, James | Staines, Anthony | Chaffee, Kari G. | Achenbach, Sara J. | Vachon, Celine M. | Goldin, Lynn R. | Strom, Sara S. | Leis, Jose F. | Weinberg, J. Brice | Caporaso, Neil E. | Norman, Aaron D. | De Roos, Anneclaire J. | Morton, Lindsay M. | Severson, Richard K. | Riboli, Elio | Vineis, Paolo | Kaaks, Rudolph | Masala, Giovanna | Weiderpass, Elisabete | Chirlaque, María- Dolores | Vermeulen, Roel C. H. | Travis, Ruth C. | Southey, Melissa C. | Milne, Roger L. | Albanes, Demetrius | Virtamo, Jarmo | Weinstein, Stephanie | Clavel, Jacqueline | Zheng, Tongzhang | Holford, Theodore R. | Villano, Danylo J. | Maria, Ann | Spinelli, John J. | Gascoyne, Randy D. | Connors, Joseph M. | Bertrand, Kimberly A. | Giovannucci, Edward | Kraft, Peter | Kricker, Anne | Turner, Jenny | Ennas, Maria Grazia | Ferri, Giovanni M. | Miligi, Lucia | Liang, Liming | Ma, Baoshan | Huang, Jinyan | Crouch, Simon | Park, Ju-Hyun | Chatterjee, Nilanjan | North, Kari E. | Snowden, John A. | Wright, Josh | Fraumeni, Joseph F. | Offit, Kenneth | Wu, Xifeng | de Sanjose, Silvia | Cerhan, James R. | Chanock, Stephen J. | Rothman, Nathaniel | Slager, Susan L.
Nature Communications  2016;7:10933.
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPP associated with risk of this disease.
PMCID: PMC4786871  PMID: 26956414
3.  Sodium-to-Potassium Ratio and Blood Pressure, Hypertension, and Related Factors12 
Advances in Nutrition  2014;5(6):712-741.
The potential cost-effectiveness and feasibility of dietary interventions aimed at reducing hypertension risk are of considerable interest and significance in public health. In particular, the effectiveness of restricted sodium or increased potassium intake on mitigating hypertension risk has been demonstrated in clinical and observational research. The role that modified sodium or potassium intake plays in influencing the renin-angiotensin system, arterial stiffness, and endothelial dysfunction remains of interest in current research. Up to the present date, no known systematic review has examined whether the sodium-to-potassium ratio or either sodium or potassium alone is more strongly associated with blood pressure and related factors, including the renin-angiotensin system, arterial stiffness, the augmentation index, and endothelial dysfunction, in humans. This article presents a systematic review and synthesis of the randomized controlled trials and observational research related to this issue. The main findings show that, among the randomized controlled trials reviewed, the sodium-to-potassium ratio appears to be more strongly associated with blood pressure outcomes than either sodium or potassium alone in hypertensive adult populations. Recent data from the observational studies reviewed provide additional support for the sodium-to-potassium ratio as a superior metric to either sodium or potassium alone in the evaluation of blood pressure outcomes and incident hypertension. It remains unclear whether this is true in normotensive populations and in children and for related outcomes including the renin-angiotensin system, arterial stiffness, the augmentation index, and endothelial dysfunction. Future study in these populations is warranted.
PMCID: PMC4224208  PMID: 25398734
4.  Serum IgA to Epstein-Barr virus Early Antigen-Diffuse identifies Hodgkin's Lymphoma 
Journal of medical virology  2013;86(9):1621-1628.
Hodgkin's lymphoma is associated with immune dysregulation. Immune impairment often results in aberrant immune responses and lytic reactivation of ubiquitous Herpesviruses such as Epstein-Barr virus (EBV) in mucosal tissues. Accordingly, the specificity of IgA to EBV early-lytic antigens, which are important for reactivation, was evaluated to determine Hodgkin's lymphoma-specific sero-reactive patterns. Sera from 42 previously described patients with Hodgkin's lymphoma were compared to sera from 17 patients with infectious mononucleosis (IM), another EBV-related condition that often presents in a similar manner; and to sera from 15 healthy EBV-seropositive subjects. Flow cytometry analysis demonstrated that like IM sera, most Hodgkin's lymphoma sera contained IgA that labeled cells expressing EBV early-lytic antigens whereas healthy EBV-seropositive sera did not. Further evaluation to distinguish Hodgkin's lymphoma from IM showed that IgA in most Hodgkin's lymphoma, irrespective of the presence of EBV in primary tumors, detected only modified forms of EBV lytic Early Antigen-Diffuse (EA-D) while IM sera detected the un-modified form as well, further supporting the presence of immune dysregulation in Hodgkin's lymphoma patients. This IgA pattern distinguished Hodgkin's lymphoma from IM sera with a sensitivity of 92.9%, specificity 100%, positive predictive value 100%, and negative predictive value 85%. Our findings lay the groundwork for additional scientific and clinical investigation, particularly into the potential for developing Hodgkin's lymphoma -associated diagnostic and prognostic biomarkers.
PMCID: PMC3969873  PMID: 24122847
Hodgkin's lymphoma; Epstein-Barr virus; immune dysregulation; biomarker; lytic antigens
5.  Medical History, Lifestyle, Family History, and Occupational Risk Factors for Sporadic Burkitt Lymphoma/Leukemia: The Interlymph Non-Hodgkin Lymphoma Subtypes Project 
The etiologic role of medical history, lifestyle, family history, and occupational risk factors in sporadic Burkitt lymphoma (BL) is unknown, but epidemiologic and clinical evidence suggests that risk factors may vary by age.
We investigated risk factors for sporadic BL in 295 cases compared with 21818 controls in a pooled analysis of 18 case–control studies in the International Lymphoma Epidemiology Consortium (InterLymph). Cases were defined to include typical BL or Burkitt-like lymphoma. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations were calculated separately for younger (<50 years) and older (≥50 years) BL using multivariate logistic regression.
Cases included 133 younger BL and 159 older BL (age was missing for three cases) and they were evenly split between typical BL (n = 147) and Burkitt-like lymphoma (n = 148). BL in younger participants was inversely associated with a history of allergy (OR = 0.58; 95% CI = 0.32 to 1.05), and positively associated with a history of eczema among individuals without other atopic conditions (OR = 2.54; 95% CI = 1.20 to 5.40), taller height (OR = 2.17; 95% CI = 1.08 to 4.36), and employment as a cleaner (OR = 3.49; 95% CI = 1.13 to 10.7). BL in older participants was associated with a history of hepatitis C virus seropositivity (OR = 4.19; 95% CI = 1.05 to 16.6) based on three exposed cases. Regardless of age, BL was inversely associated with alcohol consumption and positively associated with height.
Our data suggest that BL in younger and older adults may be etiologically distinct.
PMCID: PMC4155458  PMID: 25174031
6.  Medical History, Lifestyle, Family History, and Occupational Risk Factors for Mycosis Fungoides and Sézary Syndrome: The InterLymph Non-Hodgkin Lymphoma Subtypes Project 
Mycosis fungoides and Sézary syndrome (MF/SS) are rare cutaneous T-cell lymphomas. Their etiology is poorly understood.
A pooled analysis of 324 MF/SS cases and 17217 controls from 14 case–control studies from Europe, North America, and Australia, as part of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma (NHL) Subtypes Project, was carried out to investigate associations with lifestyle, medical history, family history, and occupational risk factors. Multivariate logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).
We found an increased risk of MF/SS associated with body mass index equal to or larger than 30kg/m2 (OR = 1.57, 95% CI = 1.03 to 2.40), cigarette smoking for 40 years or more (OR = 1.55, 95% CI = 1.04 to 2.31), eczema (OR = 2.38, 95% CI = 1.73 to 3.29), family history of multiple myeloma (OR = 8.49, 95% CI = 3.31 to 21.80), and occupation as crop and vegetable farmers (OR = 2.37, 95% CI = 1.14 to 4.92), painters (OR = 3.71, 95% CI = 1.94 to 7.07), woodworkers (OR = 2.20, 95% CI = 1.18 to 4.08), and general carpenters (OR = 4.07, 95% CI = 1.54 to 10.75). We also found a reduced risk of MF/SS associated with moderate leisure time physical activity (OR = 0.46, 95% CI = 0.22 to 0.97).
Our study provided the first detailed analysis of risk factors for MF/SS and further investigation is needed to confirm these findings in prospective data and in other populations.
PMCID: PMC4155463  PMID: 25174030
7.  Medical History, Lifestyle, Family History, and Occupational Risk Factors for Peripheral T-Cell Lymphomas: The InterLymph Non-Hodgkin Lymphoma Subtypes Project 
Accounting for 10%–15% of all non-Hodgkin lymphomas in Western populations, peripheral T-cell lymphomas (PTCL) are the most common T-cell lymphoma but little is known about their etiology. Our aim was to identify etiologic risk factors for PTCL overall, and for specific PTCL subtypes, by analyzing data from 15 epidemiologic studies participating in the InterLymph Consortium.
A pooled analysis of individual-level data for 584 histologically confirmed PTCL cases and 15912 controls from 15 case–control studies conducted in Europe, North America, and Australia was undertaken. Data collected from questionnaires were harmonized to permit evaluation of a broad range of potential risk factors. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression.
Risk factors associated with increased overall PTCL risk with a P value less than .05 included: a family history of hematologic malignancies (OR = 1.92, 95% CI = 1.30 to 2.84); celiac disease (OR = 17.8, 95% CI = 8.61 to 36.79); eczema (OR = 1.41, 95% CI = 1.07 to 1.85); psoriasis (OR = 1.97, 95% CI = 1.17 to 3.32); smoking 40 or more years (OR = 1.92, 95% CI = 1.41 to 2.62); and employment as a textile worker (ever) (OR = 1.58, 95% CI = 1.05 to 2.38) and electrical fitter (ever) (OR = 2.89, 95% CI = 1.41 to 5.95). Exposures associated with reduced overall PTCL risk included a personal history of allergies (OR = 0.69, 95% CI = 0.54 to 0.87), alcohol consumption (ever) (OR = 0.64, 95% CI = 0.49 to 0.82), and having ever lived or worked on a farm (OR = 0.72, 95% CI = 0.55% to 0.95%). We also observed the well-established risk elevation for enteropathy-type PTCL among those with celiac disease in our data.
Conclusions Our pooled analyses identified a number of new potential risk factors for PTCL and require further validation in independent series.
PMCID: PMC4155466  PMID: 25174027
8.  Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project 
Morton, Lindsay M. | Slager, Susan L. | Cerhan, James R. | Wang, Sophia S. | Vajdic, Claire M. | Skibola, Christine F. | Bracci, Paige M. | de Sanjosé, Silvia | Smedby, Karin E. | Chiu, Brian C. H. | Zhang, Yawei | Mbulaiteye, Sam M. | Monnereau, Alain | Turner, Jennifer J. | Clavel, Jacqueline | Adami, Hans-Olov | Chang, Ellen T. | Glimelius, Bengt | Hjalgrim, Henrik | Melbye, Mads | Crosignani, Paolo | di Lollo, Simonetta | Miligi, Lucia | Nanni, Oriana | Ramazzotti, Valerio | Rodella, Stefania | Costantini, Adele Seniori | Stagnaro, Emanuele | Tumino, Rosario | Vindigni, Carla | Vineis, Paolo | Becker, Nikolaus | Benavente, Yolanda | Boffetta, Paolo | Brennan, Paul | Cocco, Pierluigi | Foretova, Lenka | Maynadié, Marc | Nieters, Alexandra | Staines, Anthony | Colt, Joanne S. | Cozen, Wendy | Davis, Scott | de Roos, Anneclaire J. | Hartge, Patricia | Rothman, Nathaniel | Severson, Richard K. | Holly, Elizabeth A. | Call, Timothy G. | Feldman, Andrew L. | Habermann, Thomas M. | Liebow, Mark | Blair, Aaron | Cantor, Kenneth P. | Kane, Eleanor V. | Lightfoot, Tracy | Roman, Eve | Smith, Alex | Brooks-Wilson, Angela | Connors, Joseph M. | Gascoyne, Randy D. | Spinelli, John J. | Armstrong, Bruce K. | Kricker, Anne | Holford, Theodore R. | Lan, Qing | Zheng, Tongzhang | Orsi, Laurent | Dal Maso, Luigino | Franceschi, Silvia | La Vecchia, Carlo | Negri, Eva | Serraino, Diego | Bernstein, Leslie | Levine, Alexandra | Friedberg, Jonathan W. | Kelly, Jennifer L. | Berndt, Sonja I. | Birmann, Brenda M. | Clarke, Christina A. | Flowers, Christopher R. | Foran, James M. | Kadin, Marshall E. | Paltiel, Ora | Weisenburger, Dennis D. | Linet, Martha S. | Sampson, Joshua N.
Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.
We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case–control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).
Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10−4), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10−4). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.
Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.
PMCID: PMC4155467  PMID: 25174034
9.  Medical training fails to prepare providers to care for patients with chronic hepatitis B infection 
AIM: To investigate physicians’ knowledge including chronic hepatitis B (CHB) diagnosis, screening, and management in various stages of their training.
METHODS: A voluntary 20-question survey was administered in Santa Clara County, CA where Asian and Pacific Islanders (API) account for a third of the population. Among the 219 physician participants, there were 63 interns, 60 second-year residents, 26 chief residents and 70 attending physicians. The survey asked questions regarding respondents’ demographics, general hepatitis B virus knowledge questions (i.e., transmission, prevalence, diagnostic testing, prevention, and treatment options), as well as, self-reported practice behavior and confidence in knowledge.
RESULTS: Knowledge about screening and managing patients with CHB was poor: only 24% identified the correct tests to screen for CHB, 13% knew the next steps for patients testing positive for CHB, 18% knew the high prevalence rate among API, and 31% knew how to screen for liver cancer. Wald chi-square analysis determined the effect of training level on knowledge; in all cases except for knowledge of liver cancer screening (P = 0.0032), knowledge did not significantly increase with length in residency training or completion of residency.
CONCLUSION: Even in a high-risk region, both medical school and residency training have not adequately prepared physicians in the screening and management of CHB.
PMCID: PMC4462732  PMID: 26078568
Liver cancer; Hepatitis B; Asian Pacific Islander; Liver disease; Health disparity
10.  Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry 
The distribution of breast cancer molecular subtypes has been shown to vary by race/ethnicity, highlighting the importance of host factors in breast tumor biology. We undertook the current analysis to determine population-based distributions of breast cancer subtypes among six ethnic Asian groups in California. We defined immunohistochemical (IHC) surrogates for each breast cancer subtype among Chinese, Japanese, Filipina, Korean, Vietnamese, and South Asian patients diagnosed with incident, primary, invasive breast cancer between 2002 and 2007 in the California Cancer Registry as: hormone receptor-positive (HR+)/HER2− [estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-negative (HER2−)], triple-negative (ER−, PR−, and HER2−), and HER2-positive (ER±, PR±, and HER2+). We calculated frequencies of breast cancer subtypes among Asian ethnic groups and evaluated their associations with clinical and demographic factors. Complete IHC data were available for 8,140 Asian women. Compared to non-Hispanic White women, Korean [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5–2.2], Filipina (OR = 1.3, 95% CI = 1.2–1.5), Vietnamese (OR = 1.3, 95% CI = 1.1–1.6), and Chinese (OR =1.1, 95% CI = 1.0–1.3) women had a significantly increased risk of being diagnosed with HER2-positive breast cancer subtypes after adjusting for age, stage, grade, socioeconomic status, histology, diagnosis year, nativity, and hospital ownership status. We report a significant ethnic disparity in HER2-positive breast cancer in a large population-based cohort enriched for Asian-Americans. Given the poor prognosis and high treatment costs of HER2-positive breast cancer, our results have implications for healthcare resource utilization, cancer biology, and clinical care.
PMCID: PMC4349378  PMID: 20957431
Breast cancer subtypes; Asian; Ethnicity; HER2-positive breast cancer; Hormone receptor-positive breast cancer; Triple-negative breast cancer
Head & neck  2010;32(10):1336-1344.
Our aim was to determine the incidence rates of head and neck cancer in Vietnamese Californians compared with other Asian and non-Asian Californians.
Age-adjusted incidence rates of head and neck cancer between 1988 and 2004 were computed for Vietnamese Californians compared with other racial/ethnic groups by time period, ethnicity, neighborhood-level socioeconomic status (SES), and sex using data from the population-based California Cancer Registry (CCR). Data by smoking and alcohol status were tabulated from the California Health Interview Survey.
Vietnamese men had a higher incidence rate of head and neck cancer than other Asian men. Specifically, the laryngeal cancer rate was significantly higher for Vietnamese men (6.5/100,000; 95% confidence interval [CI], 5.0–8.2) than all other Asian men (range, 2.6–3.8/100,000), except Korean men (5.1/100,000; 95% CI, 3.9–6.4). Both Vietnamese and Korean men had the highest percentage of current smokers. Neighborhood SES was inversely related to head and neck cancer rates among Vietnamese men and women.
The higher incidence rate of head and neck cancer in Vietnamese men may correspond to the higher smoking prevalence in this group. Individual-level data are needed to establish the link of tobacco, alcohol, and other risk factors with head and neck cancer in these patients.
PMCID: PMC4349526  PMID: 20091688
head and neck cancer; Vietnamese; tobacco; socioeconomic status; immigrant status
12.  Body Mass Index and Risk of Death in Asian Americans 
American journal of public health  2014;104(3):520-525.
To investigate the association between body mass index (BMI) and mortality among Asian Americans
We pooled data from prospective cohort studies that included 20,672 Asian American adults with no history of cancer or heart disease at baseline. Hazard ratios and 95% confidence intervals (CI) were estimated using Cox proportional hazards models.
A high, but not low, BMI was associated with an increased risk of total mortality among individuals 35–69 years old. BMI was not related to total mortality among individuals ≥70 years old. With a BMI 22.5–<25 as the reference category among 35–69 year old never smokers the hazard ratios (95% CI) for total mortality were 0.83 (0.47–1.47) for BMI 15–<18.5, 0.91 (0.62–1.32) for BMI 18.5–<20, 1.08 (0.86–1.36) for BMI 20–<22.5, 1.14 (0.90–1.44) for BMI 25–<27.5, 1.13 (0.79–1.62) for BMI 27.5–<30, 1.82 (1.25–2.64) for BMI 30–<35, and 2.09 (1.06–4.11) for BMI 35–50. Higher BMI was also related to an increased mortality from cardiovascular disease and cancer.
A high BMI is associated with increased risk of mortality among Asian Americans.
PMCID: PMC3953786  PMID: 24432919
13.  Dose-Response Relationship Between Serum 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Diabetes Mellitus: A Meta-Analysis 
American Journal of Epidemiology  2015;181(6):374-384.
We systematically evaluated studies published through May 2014 in which investigators assessed the dose-response relationship between serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the occurrence of diabetes mellitus (DM), and we investigated the extent and sources of interstudy heterogeneity. The dose-response relationship between serum TCDD and DM across studies was examined using 2 dependent variables: an exposure level–specific proportion of persons with DM and a corresponding natural log-transformed ratio measure of the association between TCDD and DM. Regression slopes for each dependent variable were obtained for each study and included in a random-effects meta-analysis. Sensitivity analyses were used to assess the influence of inclusion and exclusion decisions, and sources of heterogeneity were explored using meta-regression models and a series of subanalyses. None of the summary estimates in the main models or in the sensitivity analyses indicated a statistically significant association. We found a pronounced dichotomy: a positive dose-response in cross-sectional studies of populations with low-level TCDD exposures (serum concentrations <10 pg/g lipid) and heterogeneous, but on balance null, results for prospective studies of persons with high prediagnosis TCDD body burdens. Considering the discrepancy of results for low current versus high past TCDD levels, the available data do not indicate that increasing TCDD exposure is associated with an increased risk of DM.
PMCID: PMC4380020  PMID: 25731889
Agent Orange; diabetes mellitus; dioxin; dose-response; heterogeneity; meta-analysis; TCDD
14.  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
15.  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
16.  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
17.  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
18.  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
19.  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
20.  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
21.  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
22.  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
23.  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
24.  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
25.  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

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