Publications by authors named "Brenda M Birmann"

75 Publications

Correlates of COVID-19 vaccine hesitancy in Austria: trust and the government.

J Public Health (Oxf) 2021 May 5. Epub 2021 May 5.

Complexity Science Hub, 1080 Vienna, Austria.

Background: With the coronavirus disease 2019 (COVID-19) pandemic surging and new mutations evolving, trust in vaccines is essential.

Methods: We explored correlates of vaccine hesitancy, considering political believes and psychosocial concepts, conducting a non-probability quota-sampled online survey with 1007 Austrians.

Results: We identified several important correlates of vaccine hesitancy, ranging from demographics to complex factors such as voting behavior or trust in the government. Among those with hesitancy towards a COVID-19 vaccine, having voted for opposition parties (opp) or not voted (novote) were (95% Confidence Intervall (CI)opp, 1.44-2.95) to 2.25-times (95%CInovote, 1.53-3.30) that of having voted for governing parties. Only 46.2% trusted the Austrian government to provide safe vaccines, and 80.7% requested independent scientific evaluations regarding vaccine safety to increase willingness to vaccine.

Conclusions: Contrary to expected, psychosocial dimensions were only weakly correlated with vaccine hesitancy. However, the strong correlation between distrust in the vaccine and distrust in authorities suggests a common cause of disengagement from public discourse.
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http://dx.doi.org/10.1093/pubmed/fdab122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135852PMC
May 2021

Working from home, quality of life, and perceived productivity during the first 50-day COVID-19 mitigation measures in Austria: a cross-sectional study.

Int Arch Occup Environ Health 2021 Apr 20. Epub 2021 Apr 20.

Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria.

Objectives: To explore changes in quality of life and perceived productivity, focusing on the effects of working from home during the first COVID-19 50-day mitigation period in Austria.

Methods: We conducted an Austrian-representative online survey (N = 1010) of self-reported life- and work-related changes during the first COVID-19 50-day mitigation period (March 16 through May 1 2020) compared to the situation before. We used multinominal logistic regression models to identify correlates of improved/decreased quality of life in the entire sample, and of improved/decreased productivity in a subsample of the working population (N = 686). We also calculated age- and multivariable-adjusted ORs and 95% CIs of an improved/decreased quality of life and an improved/decreased productivity by work from home status.

Results: During the COVID-19 mitigation period, quality of life improved in 17.5%, but decreased in 20.7% of the general Austrian population; perceived productivity at work increased in 12.7%, but decreased in 30.2% of the working population. Working from home during the mitigation period was associated with an increased quality of life (vs. none, partially: OR 2.07, 95% CI 1.09-3.91; all the time: 3.69, 1.86-7.29). In contrast, perceived productivity seemed to decrease when people worked from home (vs. none, partially: 1.42, 0.86-2.35; all the time: 1.48, 0.85-2.58). Working from home and related benefits were not equally distributed among gender, age, and educational attainment.

Conclusions: A transition to more flexibility of workplace and working hours for employees could have important positive consequences for family and professional life, for stakeholders, for public health, and ultimately for the environment.
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http://dx.doi.org/10.1007/s00420-021-01692-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056371PMC
April 2021

Comment on Alley, S.J., et al. As the Pandemic Progresses, How Does Willingness to Vaccinate against COVID-19 Evolve? 2021, , 797.

Int J Environ Res Public Health 2021 03 10;18(6). Epub 2021 Mar 10.

Department of Epidemiology, Medical University of Vienna, 1090 Vienna, Austria.

We would like to extend on the article by Alley et al [...].
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http://dx.doi.org/10.3390/ijerph18062809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001093PMC
March 2021

Circulating Biomarkers of Inflammation and Ovarian Cancer Risk in the Nurses' Health Studies.

Cancer Epidemiol Biomarkers Prev 2021 Apr 9;30(4):710-718. Epub 2021 Feb 9.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: Chronic inflammation is a well-established mechanism of ovarian carcinogenesis; however, the specific immunogenic processes influencing ovarian tumor development remain unclear. In a case-control study nested within the Nurses' Health Study (NHS) and the NHSII, we examined the association between six inflammatory chemokines and cytokines [B-cell activating factor (BAFF), C-X-C motif chemokine ligand 13 (CXCL13), IL8, soluble(s)IL2-receptor-α(Rα), sIL6Rα] and epithelial ovarian cancer risk.

Methods: Among 299 epithelial ovarian cancer cases and 334 matched controls, six inflammatory biomarkers were measured in plasma collected 1-24 years before diagnosis or index date using two custom multiplex Luminex panels. ORs and 95% confidence intervals (CI) were estimated for the association between each biomarker and risk using multivariable conditional logistic regression with adjustment for relevant confounders. We additionally assessed heterogeneity in the risk associations by histotype [high-grade serous carcinoma (HGSC) vs. non-HGSC], body mass index, smoking status, menopausal status, and aspirin use.

Results: Women with the highest versus lowest quartile (Q) levels of CXCL13 had a 72% increased ovarian cancer risk (OR = 1.72; 95% CI = 1.04-2.83; = 0.007). The positive association with CXCL13 was stronger in magnitude for non-HGSC, overweight or obese women, and postmenopausal women, although only menopausal status demonstrated statistically significant heterogeneity ( = 0.04). The remaining biomarkers were not associated with risk.

Conclusions: This first evidence that prediagnostic CXCL13, a B-cell chemoattractant, is associated with an increased risk of epithelial ovarian cancer expands current understanding of the role of inflammation in ovarian carcinogenesis.

Impact: CXCL13 may represent a novel biomarker for ovarian cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1390DOI Listing
April 2021

Red blood cell membrane trans fatty acid levels and risk of non-Hodgkin lymphoma: a prospective nested case-control study.

Am J Clin Nutr 2020 12;112(6):1576-1583

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Background: Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk.

Objectives: To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes.

Methods: We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989-1090 and 1994-1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013-2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression.

Results: Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk [n = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P = 0.015], driven by trans 18:1n-9(ω-9)/elaidic acid [OR (95% CI): 1.34 (1.08, 1.66); P = 0.007], trans 18:1n-7/vaccenic acid [OR (95% CI): 1.28 (1.04, 1.58); P = 0.023], and trans 18:2n-6t,t [OR (95% CI): 1.26 (1.01, 1.57); P = 0.037].

Conclusions: Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype.
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http://dx.doi.org/10.1093/ajcn/nqaa251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727472PMC
December 2020

Personal use of permanent hair dyes and cancer risk and mortality in US women: prospective cohort study.

BMJ 2020 09 2;370:m2942. Epub 2020 Sep 2.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

Objective: To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality.

Design: Prospective cohort study.

Setting And Participants: 117 200 women enrolled in the Nurses' Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years.

Exposure: Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes.

Main Outcome Measures: Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models.

Results: Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair.

Conclusion: No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.
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http://dx.doi.org/10.1136/bmj.m2942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463170PMC
September 2020

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Nat Commun 2020 07 3;11(1):3353. Epub 2020 Jul 3.

Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
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http://dx.doi.org/10.1038/s41467-020-16483-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335068PMC
July 2020

Association between yogurt consumption and plasma soluble CD14 in two prospective cohorts of US adults.

Eur J Nutr 2021 Mar 16;60(2):929-938. Epub 2020 Jun 16.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Purpose: Although evidence suggests an inverse association between yogurt consumption and the risk of disorders, such as type 2 diabetes and certain cancers, the mechanisms remain poorly understood. We aimed to examine the association between yogurt consumption and concentrations of plasma soluble CD14, a marker of gut barrier dysfunction.

Methods: We analyzed cross-sectional data from 632 women in the Nurses' Health Study (1989-1990) and 444 men in the Health Professionals Follow-up Study (1993-1994) with soluble CD14 concentrations. We estimated yogurt consumption from food frequency questionnaires. We used multivariable-adjusted linear regression models to estimate the percentage difference (95% CI) of soluble CD14 concentrations by yogurt consumption.

Results: Among men, higher consumption was associated with a lower soluble CD14 concentration (at least 2 cups/week vs. non-consumers; unadjusted % difference: - 7.6%; 95% CI - 13.0%, - 2.1%; P = 0.003). The inverse association was slightly attenuated following multivariable adjustment (% difference: - 5.8%; 95% CI - 11.0%, - 0.1%; P = 0.01). For the same comparison, yogurt consumption was inverse, but not statistically significant associated with soluble CD14 concentration in women (% difference: - 1.2%; 95% CI - 5.6%, 3.5%; P = 0.64). In stratified analyses, the inverse association between yogurt consumption and the concentrations of soluble CD14 was slightly stronger in men who consumed alcohol at least 20 g/day.

Conclusions: Higher yogurt consumption was associated with lower soluble CD14 concentrations, especially in men. Our findings suggest the strengthening of gut barrier function as a plausible mechanism for the observed inverse associations of yogurt consumption with gastrointestinal diseases and disorders involving other systems.
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http://dx.doi.org/10.1007/s00394-020-02303-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738354PMC
March 2021

Rotating Nightshift Work and Hematopoietic Cancer Risk in US Female Nurses.

JNCI Cancer Spectr 2020 Apr 8;4(2):pkz106. Epub 2020 Jan 8.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Nightshift work is a plausible risk factor for hematologic cancer, but epidemiological evidence remains sparse, especially for individual subtypes. We prospectively examined the association of rotating nightshift work with hematopoietic cancer risk.

Methods: This cohort study included US women from the Nurses' Health Study (NHS: n = 76 846, 1988-2012) and Nurses' Health Study II (NHSII: n = 113 087, 1989-2013). Rotating nightshift work duration was assessed at baseline (both cohorts) and cumulatively updated (NHSII). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall hematopoietic cancer and specific histologic subtypes. All statistical tests were two-sided.

Results: We documented 1405 (NHS) and 505 (NHSII) incident hematopoietic cancer cases during follow-up. In NHS, compared with women who never worked rotating nightshifts, longer rotating nightshift work duration was associated with an increased risk of overall hematopoietic cancer (HR = 0.93, 95% CI = 0.83 to 1.04; HR = 1.28, 95% CI = 1.06 to 1.55; = .009). In NHSII, results were similar though not statistically significant (HR = 0.99, 95% CI = 0.82 to 1.21; HR = 1.41, 95% CI = 0.88 to 2.26; = .47). In the subtype analyses in the NHS, the association of history of rotating nightshift work with risk of diffuse large B-cell lymphoma varied by duration (HR = 0.71, 95% CI = 0.51 to 0.98; HR = 1.69, 95% CI = 1.07 to 2.67; = .01) compared with those who never worked rotating nightshifts. Women reporting a longer history of rotating nightshifts also had suggestive (statistically nonsignificant) increased risks of overall non-Hodgkin lymphoma (HR = 1.19, 95% CI = 0.95 to 1.49), Hodgkin lymphoma (HR = 1.32, 95% CI = 0.43 to 4.06), and multiple myeloma (HR = 1.42, 95% CI = 0.85 to 2.39).

Conclusions: Longer duration (≥15 years) of rotating nightshift work was associated with increased risks of overall and several subtypes of hematopoietic cancer.
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http://dx.doi.org/10.1093/jncics/pkz106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073913PMC
April 2020

Statin use is associated with improved survival in multiple myeloma: A Swedish population-based study of 4315 patients.

Am J Hematol 2020 06 20;95(6):652-661. Epub 2020 Mar 20.

Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Statin use has been associated with reduced cancer-specific mortality among patients with several cancer types, including multiple myeloma (MM). We aimed to further elucidate the association of statin use and dose intensity with MM survival. Using Swedish population-based national health registers, we identified all incident MM diagnoses occurring January 1, 2007 to December 31, 2013 and their drug dispensations and comorbidities. We assessed statin exposure in 6-month periods pre- and post-diagnosis, treated diagnosis as baseline for calculating survival time, and calculated hazard ratios (HR) and 95% confidence intervals (CI) of exposure-related MM-specific and all-cause mortality using Cox regression. We assessed statin exposure during the entire follow-up and risk of MM-specific mortality in a nested case-control analysis. We classified dose intensity according to American College of Cardiology/American Heart Association recommendations. We ascertained 4315 MM cases during follow-up. Statin use was associated with reduced MM-specific mortality (pre-diagnosis use multivariate-adjusted HR, 95% CI: 0.83, 0.71-0.96; 6 months post-diagnosis: 0.73, 0.60-0.89; entire follow-up: 0.65, 0.52-0.80) and (more weakly) with all-cause mortality. Intensity analyses suggested a dose-response; MM-specific mortality decreased with increasing statin intensity in all time windows (eg, 6 months post-diagnosis: low [0.76 (0.56-1.03)], medium [0.73 (0.58-0.92)], high [0.33 (0.08-1.32)] intensity). However, relatively few patients received high intensity treatment, and the trend was statistically significant only for unadjusted pre-diagnosis use. In this large population-based MM cohort, statin use was associated with improved MM-specific survival in both sexes. Randomized prospective studies are warranted to evaluate statins as adjuvant treatment in MM.
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http://dx.doi.org/10.1002/ajh.25778DOI Listing
June 2020

Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.

Cancer Epidemiol Biomarkers Prev 2020 05 27;29(5):1074-1078. Epub 2020 Feb 27.

Emory University, Atlanta, Georgia.

Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis.

Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated ( < 5 × 10) with high-density lipoprotein (HDL, = 164), low-density lipoprotein (LDL, = 137), total cholesterol (TC, = 161), and triglycerides (TG, = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI).

Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance ( < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; = 0.087). No associations were noteworthy after adjusting for multiple testing.

Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes.

Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196490PMC
May 2020

Prediagnosis dietary pattern and survival in patients with multiple myeloma.

Int J Cancer 2020 10 28;147(7):1823-1830. Epub 2020 Feb 28.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Inflammation and endogenous growth factors are important in multiple myeloma (MM) pathogenesis. Although diets that modulate these biologic pathways may influence MM patient survival, studies have not examined the association of dietary patterns with MM survival. We conducted pooled prospective survival analyses of 423 MM patients from the Nurses' Health Study (1986-2016) and the Health Professionals Follow-up Study (1988-2016) using Cox regression models. We used data from repeated food frequency questionnaires (FFQ) to compute dietary patterns as of the last prediagnosis FFQ, including the Alternate Healthy Eating Index (AHEI)-2010, alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension, Prudent, Western and empirical dietary inflammatory patterns and empirical dietary indices for insulin resistance and hyperinsulinemia. During follow-up, we documented 295 MM-related deaths among 345 total deaths. MM-specific mortality was 15-24% lower per one standard deviation (SD) increase (e.g., toward healthier habits) in favorable dietary pattern scores. For example, the multivariable-adjusted hazard ratio [HR] and 95% confidence interval [CI] per 1-SD increase in AHEI-2010 score were 0.76, 0.67-0.87 (p < 0.001). In contrast, MM-specific mortality was 16-24% higher per 1-SD increase (e.g., toward less healthy habits) in "unhealthy" diet scores; for example, the multivariable-adjusted HR, 95% CI per 1-SD increase in Western pattern score were 1.24, 1.07-1.44 (p = 0.005). Associations were similar for all-cause mortality. In conclusion, our consistent findings for multiple dietary patterns provide the first evidence that MM patients with healthier prediagnosis dietary habits may have longer survival than those with less healthy diets.
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http://dx.doi.org/10.1002/ijc.32928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423719PMC
October 2020

Dissecting racial disparities in multiple myeloma.

Blood Cancer J 2020 02 17;10(2):19. Epub 2020 Feb 17.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.

Multiple myeloma (MM) is a fatal plasma cell dyscrasia with a median overall survival of 5 to 10 years. MM progresses from the more common but often subclinical precursor states of monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM) to overt MM. There are large racial disparities in all stages of the disease. Compared with Whites, Blacks have an increased MGUS and MM risk and higher mortality rate, and have not experienced the same survival gains over time. The roots of this disparity are likely multifactorial in nature. Comparisons of Black and White MGUS and MM patients suggest that differences in risk factors, biology, and clinical characteristics exist by race or ancestry, which may explain some of the observed disparity in MM. However, poor accrual of Black MGUS and MM patients in clinical and epidemiological studies has limited our understanding of this disparity and hindered its elimination. Disparities in MM survival also exist but appear to stem from inferior treatment utilization and access rather than underlying pathogenesis. Innovative and multidisciplinary approaches are urgently needed to enhance our understanding of disparities that exist at each stage of the MM disease continuum and facilitate their elimination.
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http://dx.doi.org/10.1038/s41408-020-0284-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026439PMC
February 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Identifying monoclonal gammopathy of undetermined significance in electronic health data.

Pharmacoepidemiol Drug Saf 2020 01 17;29(1):69-76. Epub 2019 Nov 17.

The Meyers Primary Care Institute, a joint venture of Reliant Medical Group, Fallon Health, and the University of Massachusetts Medical School, Worcester, MA, USA.

Purpose: Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent yet largely asymptomatic precursor to multiple myeloma. Patients with MGUS must undergo regular surveillance and testing, with few known predictors of progression. We developed an algorithm to identify MGUS patients in electronic health data to facilitate large-scale, population-based studies of this premalignant condition.

Methods: We developed a four-step algorithm using electronic health record and health claims data from men and women aged 50 years or older receiving care from a large, multispecialty medical group between 2007 and 2015. The case definition required patients to have at least two MGUS ICD-9 diagnosis codes within 12 months, at least one serum and/or urine protein electrophoresis and one immunofixation test, and at least one in-office hematology/oncology visit. Medical charts for selected cases were abstracted then adjudicated independently by two physicians. We assessed algorithm validity by positive predictive value (PPV).

Results: We identified 833 people with at least two MGUS diagnosis codes; 429 (52%) met all four algorithm criteria. We randomly selected 252 charts for review, including 206 from patients meeting all four algorithm criteria. The PPV for the 206 algorithm-identified charts was 76% (95% CI, 70%-82%). Among the 49 cases deemed to be false positives (24%), 33 were judged to have multiple myeloma or another lymphoproliferative condition, such as lymphoma.

Conclusions: We developed a simple algorithm that identified MGUS cases in electronic health data with reasonable accuracy. Inclusion of additional steps to eliminate cases with malignant disease may improve algorithm performance.
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http://dx.doi.org/10.1002/pds.4912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365702PMC
January 2020

Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.

Hum Mol Genet 2020 01;29(1):70-79

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
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http://dx.doi.org/10.1093/hmg/ddz228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001601PMC
January 2020

Elucidating Under-Studied Aspects of the Link Between Obesity and Multiple Myeloma: Weight Pattern, Body Shape Trajectory, and Body Fat Distribution.

JNCI Cancer Spectr 2019 Sep 24;3(3):pkz044. Epub 2019 Jun 24.

See the Notes section for the full list of authors' affiliations.

Background: Although obesity is an established modifiable risk factor for multiple myeloma (MM), several nuanced aspects of its relation to MM remain unelucidated, limiting public health and prevention messages.

Methods: We analyzed prospective data from the Nurses' Health Study and Health Professionals Follow-Up Study to examine MM risk associated with 20-year weight patterns in adulthood, body shape trajectory from ages 5 to 60 years, and body fat distribution. For each aforementioned risk factor, we report hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MM from multivariable Cox proportional-hazards models.

Results: We documented 582 incident MM cases during 4 280 712 person-years of follow-up. Persons who exhibited extreme weight cycling, for example, those with net weight gain and one or more episodes of intentional loss of at least 20 pounds or whose cumulative intentional weight loss exceeded net weight loss with at least one episode of intentional loss of 20 pounds or more had an increased MM risk compared with individuals who maintained their weight (HR = 1.71, 95% CI = 1.05 to 2.80); the association was statistically nonsignificant after adjustment for body mass index. We identified four body shape trajectories: lean-stable, lean-increase, medium-stable, and medium-increase. MM risk was higher in the medium-increase group than in the lean-stable group (HR = 1.62, 95% CI = 1.22 to 2.14). Additionally, MM risk increased with increasing hip circumference (HR per 1-inch increase: 1.03, 95% CI = 1.01 to 1.06) but was not associated with other body fat distribution measures.

Conclusions: Maintaining a lean and stable weight throughout life may provide the strongest benefit in terms of MM prevention.
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http://dx.doi.org/10.1093/jncics/pkz044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699596PMC
September 2019

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Genet Epidemiol 2019 10 13;43(7):844-863. Epub 2019 Aug 13.

Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019

Dietary Pattern and Risk of Multiple Myeloma in Two Large Prospective US Cohort Studies.

JNCI Cancer Spectr 2019 Jun 27;3(2):pkz025. Epub 2019 Apr 27.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background: The limited data on specific dietary components and risk of multiple myeloma (MM) show no consistent association. Studies have not examined the association of dietary pattern with MM risk.

Methods: In prospective cohorts of 69 751 women (Nurses' Health Study, 1984-2014) and 47 232 men (Health Professionals Follow-up Study, 1986-2014), we examined the association between dietary pattern and risk of MM using Cox proportional hazard models. Diet was assessed repeatedly every 4 years with food frequency questionnaires and was used to calculate dietary patterns including the Alternate Healthy Eating Index-2010, Alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension, Prudent and Western patterns, the empirical dietary inflammatory pattern (EDIP), and empirical dietary indices for insulin resistance (EDIR) and hyperinsulinemia (EDIH).

Results: During 2 792 257 person-years of follow-up, we identified 478 incident MM cases (215 women, 263 men). In men, high EDIP was statistically significantly associated with a 16% increase in MM risk (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 1.02 to 1.32 per 1-SD increase). Moreover, EDIR and EDIH had a suggestive positive association (EDIR: HR = 1.09, 95% CI = 0.96 to 1.24; and EDIH: HR = 1.11, 95% CI = 0.97 to 1.28 per 1-SD increase). We observed no other associations with MM risk in men and no associations for any dietary pattern with MM risk in women.

Conclusions: We present the first evidence for a role of diets with higher inflammatory or insulinemic potential in MM development. Further studies are warranted to explore these associations in other populations, including the apparent restriction to men.
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http://dx.doi.org/10.1093/jncics/pkz025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532330PMC
June 2019

Clonal hematopoiesis and risk of acute myeloid leukemia.

Haematologica 2019 12 19;104(12):2410-2417. Epub 2019 Apr 19.

Department of Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine, Saint Louis, MO

Nearly all adults harbor acute myeloid leukemia (AML)-related clonal hematopoietic mutations at a variant allele fraction (VAF) of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow up to investigate associations of clonal mutations of ≥0.0001 allele frequency with future risk of AML. We identified 35 cases with AML that had pre-diagnosis peripheral blood samples and matched two controls without history of cancer per case by sex, age, and ethnicity. We conducted blinded error-corrected sequencing on all study samples and assessed variant-associated risk using conditional logistic regression. We detected AML-associated mutations in 97% of all participants (598 mutations, 5.8/person). Individuals with mutations ≥0.01 variant allele fraction had a significantly increased AML risk (OR 5.4, 95%CI: 1.8-16.6), as did individuals with higher-frequency clones and those with R882H/C mutations. The risk of lower-frequency clones was less clear. In the 11 case-control sets with samples banked ten years apart, clonal mutations rarely expanded over time. Our findings are consistent with published evidence that detection of clonal mutations ≥0.01 VAF identifies individuals at increased risk for AML. Further study of larger populations, mutations co-occurring within the same pre-leukemic clone and other risk factors (lifestyle, epigenetics, etc.), are still needed to fully elucidate the risk conferred by low-frequency clonal hematopoiesis in asymptomatic adults.
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http://dx.doi.org/10.3324/haematol.2018.215269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959179PMC
December 2019

Trends in cause of death among patients with multiple myeloma in Puerto Rico and the United States SEER population, 1987-2013.

Int J Cancer 2020 01 30;146(1):35-43. Epub 2019 Mar 30.

Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA.

Multiple myeloma (MM) survival has improved due to recent developments in MM treatment. As a result, other co-morbid conditions may be of increasing importance to MM patients' long-term survival. This study examines trends in common causes of death among patients with MM in Puerto Rico, and in the US Surveillance, Epidemiology, and End Results (SEER) population. We analyzed the primary cause of death among incident MM cases recorded in the Puerto Rico Central Cancer Registry (n = 3,018) and the US SEER Program (n = 67,733) between 1987 and 2013. We calculated the cumulative incidence of death due to the eight most common causes and analyzed temporal trends in mortality rates using joinpoint regression. Analyses of SEER were also stratified by Hispanic ethnicity. MM accounted for approximately 72% of all reported deaths among persons diagnosed with MM in Puerto Rico and in SEER. In both populations, the proportion of patients who died from MM decreased with increasing time since diagnosis. Age-standardized temporal trends showed a decreased MM-specific mortality rate among US SEER (annual percent change [APC] = -5.0) and Puerto Rican (APC = -1.8) patients during the study period, and particularly after 2003 in non-Hispanic SEER patients. Temporal decline in non-MM causes of death was also observed among US SEER (APC = -2.1) and Puerto Rican (APC = -0.1) populations. MM-specific mortality decreased, yet remained the predominant cause of death for individuals diagnosed with MM over a 26-year period. The most pronounced decreases in MM-specific death occurred after 2003, which suggests a possible influence of more recently developed MM therapies.
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http://dx.doi.org/10.1002/ijc.32232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708774PMC
January 2020

Rising cancer incidence in younger adults: is obesity to blame?

Lancet Public Health 2019 03 4;4(3):e119-e120. Epub 2019 Feb 4.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address:

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http://dx.doi.org/10.1016/S2468-2667(19)30017-9DOI Listing
March 2019

A Network Analysis of Biomarkers for Type 2 Diabetes.

Diabetes 2019 02 8;68(2):281-290. Epub 2018 Nov 8.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

Numerous studies have investigated individual biomarkers in relation to risk of type 2 diabetes. However, few have considered the interconnectivity of these biomarkers in the etiology of diabetes as well as the potential changes in the biomarker correlation network during diabetes development. We conducted a secondary analysis of 27 plasma biomarkers representing glucose metabolism, inflammation, adipokines, endothelial dysfunction, IGF axis, and iron store plus age and BMI at blood collection from an existing case-control study nested in the Nurses' Health Study (NHS), including 1,303 incident diabetes case subjects and 1,627 healthy women. A correlation network was constructed based on pairwise Spearman correlations of the above factors that were statistically different between case and noncase subjects using permutation tests ( < 0.0005). We further evaluated the network structure separately among diabetes case subjects diagnosed <5, 5-10, and >10 years after blood collection versus noncase subjects. Although pairwise biomarker correlations tended to have similar directions comparing diabetes case subjects to noncase subjects, most correlations were stronger in noncase than in case subjects, with the largest differences observed for the insulin/HbA and leptin/adiponectin correlations. Leptin and soluble leptin receptor were two hubs of the network, with large numbers of different correlations with other biomarkers in case versus noncase subjects. When examining the correlation network by timing of diabetes onset, there were more perturbations in the network for case subjects diagnosed >10 years versus <5 years after blood collection, with consistent differential correlations of insulin and HbA C-peptide was the most highly connected node in the early-stage network, whereas leptin was the hub for mid- or late-stage networks. Our results suggest that perturbations of the diabetes-related biomarker network may occur decades prior to clinical recognition. In addition to the persistent dysregulation between insulin and HbA, our results highlight the central role of the leptin system in diabetes development.
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http://dx.doi.org/10.2337/db18-0892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341308PMC
February 2019

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia.

Nat Commun 2018 10 10;9(1):4182. Epub 2018 Oct 10.

Epidemiology Research Program, American Cancer Society, Atlanta, 30303, GA, USA.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
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http://dx.doi.org/10.1038/s41467-018-06541-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180091PMC
October 2018

Pooled study of occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma.

Occup Environ Med 2018 11 18;75(11):798-806. Epub 2018 Aug 18.

Department of Public Health and Clinical Molecular Medicine, University of Cagliari, Cagliari, Italy.

Objectives: To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study.

Methods: We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect.

Results: Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumulative intensity exposure (vs unexposed) was associated with 42% to 63% increased risks of MM. Associations with toluene and xylene exposures were fairly consistent and robust to sensitivity analyses. The estimated effect for benzene was moderately heterogeneous between the studies. Each solvent's association with MM was stronger for exposure occurring within 20 years of diagnosis than with exposure lagged by more than 20 years.

Conclusions: Our study adds important evidence for a role of aromatic hydrocarbon solvents in causation of MM. The difficulty in disentangling individual compounds in this group and a lack of data on potential carcinogenicity of toluene and xylene, in widespread current use, underscore a need for further epidemiological evaluation.
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http://dx.doi.org/10.1136/oemed-2018-105154DOI Listing
November 2018

Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations.

Nature 2018 07 11;559(7714):350-355. Epub 2018 Jul 11.

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations, from 50 kb to 249 Mb long, that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using phase-based computational techniques (estimated false discovery rate, 6-9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3-TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5-50%). Inherited alleles at one locus appeared to affect the probability of somatic mutation, and at three other loci to be objects of positive or negative clonal selection. Several specific mosaic chromosomal alterations were strongly associated with future haematological malignancies. Our results reveal a multitude of paths towards clonal expansions with a wide range of effects on human health.
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http://dx.doi.org/10.1038/s41586-018-0321-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054542PMC
July 2018

Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies.

Haematologica 2018 10 21;103(10):1679-1687. Epub 2018 Jun 21.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses' Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated Odds Ratios (OR) and 95% Confidence Intervals (CI) per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histological subtype, stratifying additional models by years (<5, 5 to <10, ≥10) after blood draw. Soluble interleukin-2 receptor-α, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. The biomarker combinations associated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (OR: 95%CI: 0.51, 0.43-0.62) persisted more than ten years after blood draw (OR: 0.70; 95%CI: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis.
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http://dx.doi.org/10.3324/haematol.2017.183236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165815PMC
October 2018

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non-Hodgkin lymphoma.

Int J Cancer 2018 10 10;143(8):1914-1922. Epub 2018 Aug 10.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.

Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T-NHL), B cell NHL (B-NHL) and three individual B-NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B-NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0 and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T-NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B-NHLs other than CLL/SLL and for VLCSFA and MUFA with T-NHL suggest an influence of fatty acid metabolism on lymphomagenesis.
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http://dx.doi.org/10.1002/ijc.31602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158051PMC
October 2018

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes.

Cancer Res 2018 07 7;78(14):4086-4096. Epub 2018 May 7.

Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci ( trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. HLA gene diversity reduces risk for non-Hodgkin lymphoma. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-2900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065509PMC
July 2018

Risk factors for Burkitt lymphoma: a nested case-control study in the UK Clinical Practice Research Datalink.

Br J Haematol 2018 05 20;181(4):505-514. Epub 2018 Apr 20.

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression-related BL and sporadic BL. Descriptive studies of BL age-specific incidence patterns have suggested multimodal peaks near 10, 40 and 70 years of age, but the risk factors for BL at different ages are unknown. We investigated risk factors for BL in the United Kingdom among 156 BL cases and 608 matched BL-free controls identified in the Clinical Practice Research Datalink (CPRD) between 1992 and 2016. Associations with pre-diagnostic body mass index, cigarette smoking, alcohol consumption, hepatitis, Epstein-Barr virus (EBV), human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), malaria, allergic and autoimmune conditions, and prednisone use were evaluated. Overall, we identified inverse associations between smoking and BL risk, and positive associations between prior EBV infection, HIV/AIDS and prescription or use of prednisone with BL risk. In age-group stratified analyses, BL was associated with malaria exposure (vs. no exposure, odds ratio [OR] 8·00, 95% confidence interval [CI] 1·46-43·7) among those aged 20-59 years old and with hepatitis infection (vs. no infection, OR 3·41, 95% CI 1·01-11·5) among those aged 60+ years old. The effects of EBV, malaria, HIV/AIDS, prednisone and hepatitis on BL remained significant in mutually-adjusted age-group-specific analyses. No risk factors were associated with childhood BL. We report novel associations for BL in non-endemic settings.
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http://dx.doi.org/10.1111/bjh.15229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980720PMC
May 2018