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1.
J Transl Genet Genom ; 5: 200-217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34622145

RESUMO

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. Results: We discovered positive associations between FROH and CLL (ß = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (ß = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (ß = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

3.
Environ Int ; 156: 106744, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34256297

RESUMO

BACKGROUND: Conventionally grown fruits and vegetables (FVs) are the main source of general population exposure to pesticide residues. OBJECTIVE: To evaluate the relation of intake of high- and low-pesticide-residue FVs with cancer risk. METHODS: We followed 150,830 women (Nurses' Health Study, 1998-2016, and Nurses' Health Study II, 1999-2017) and 29,486 men (Health Professionals Follow-up Study, 1998-2016) without a history of cancer. We ascertained FV intake via validated food frequency questionnaires and categorized FVs as having high or low pesticide residue levels based on USDA surveillance data. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and site-specific cancer related to quintiles of high- and low-pesticide-residue FV intake. RESULTS: We documented 23,678 incident cancer cases during 2,862,118 person-years of follow-up. In the pooled multivariable analysis, neither high- nor low-pesticide-residue FV intake was associated with cancer. The HRs (95% CI) per 1 serving/day increase in intake were 0.99 (0.97-1.01) for high- and 1.01 (0.99-1.02) for low-pesticide-residue FVs. Additionally, we found no association between high-pesticide-residue FV intake and risk of specific sites, including malignancies previously linked to occupational pesticide exposure ([HR, 95% CI comparing extreme quintiles of intake] lung [1.17 (0.95-1.43)], non-Hodgkin lymphoma [0.89 (0.72-1.09)], prostate [1.31 (0.88-1.93)]) or inversely related to intake of organic foods (breasts [1.03 (0.94-1.31)]). CONCLUSIONS: These findings suggest that overall exposure to pesticides through FV intake is not related to cancer risk, although they do not rule out associations with specific chemicals or sub-types of specific cancers.


Assuntos
Neoplasias , Resíduos de Praguicidas , Praguicidas , Dieta , Seguimentos , Frutas/química , Humanos , Neoplasias/epidemiologia , Resíduos de Praguicidas/análise , Modelos de Riscos Proporcionais , Fatores de Risco , Verduras
4.
Br J Haematol ; 195(4): 552-560, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34331461

RESUMO

Statin use has been associated with reduced mortality from several cancers but also suggested, in vitro, to diminish the effectiveness of lymphoma treatments including rituximab. The present study aimed to assess the association of statin use with mortality in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). We identified all incident NHLs and CLLs in Sweden from 2007 to 2013 with subtype information in the Swedish Lymphoma and Cancer Registers. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pre- or post-diagnosis statin use (yes/no, intensity) with lymphoma-specific, cardiovascular, or all-cause mortality; and for follicular lymphoma (FL) by initial treatment strategy (active/watch-and-wait). Among 16 098 incident NHL/CLL patients, 20% used statins at diagnosis. Pre- and post-diagnosis statin use, and statin intensity were not consistently associated with any mortality outcome in patients with NHL, overall or for any subtype. For actively treated patients with FL, statin use did not appear to increase lymphoma-specific mortality (vs. non-users, HR [95% CI]after diagnosis 0·87 [0·45-1·67]). For CLL, statin use was associated with all-cause and cardiovascular but not consistently with lymphoma-specific mortality. In conclusion, statin use was not associated with improved lymphoma survival but appears safe to use during lymphoma treatment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33948665

RESUMO

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.

7.
Int Arch Occup Environ Health ; 94(8): 1823-1837, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33877416

RESUMO

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.


Assuntos
COVID-19/prevenção & controle , Eficiência , Qualidade de Vida , Teletrabalho , Adulto , Áustria/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Cancer Epidemiol Biomarkers Prev ; 30(4): 710-718, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33563649

RESUMO

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; P trend = 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 (P interaction = 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.

9.
Eur J Nutr ; 60(2): 929-938, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32548645

RESUMO

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%; Ptrend = 0.003). The inverse association was slightly attenuated following multivariable adjustment (% difference: - 5.8%; 95% CI - 11.0%, - 0.1%; Ptrend = 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%; Ptrend = 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.


Assuntos
Diabetes Mellitus Tipo 2 , Receptores de Lipopolissacarídeos , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Iogurte
10.
Am J Clin Nutr ; 112(6): 1576-1583, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022699

RESUMO

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.


Assuntos
Membrana Eritrocítica/química , Linfoma não Hodgkin , Ácidos Graxos trans/química , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
11.
BMJ ; 370: m2942, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878860

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Tinturas para Cabelo/efeitos adversos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Adulto , Neoplasias Encefálicas/induzido quimicamente , Neoplasias da Mama/induzido quimicamente , Carcinoma Basocelular/induzido quimicamente , Estudos de Casos e Controles , Neoplasias Colorretais/induzido quimicamente , Feminino , Humanos , Neoplasias Renais/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Ovarianas/induzido quimicamente , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/induzido quimicamente
12.
Nat Commun ; 11(1): 3353, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620889

RESUMO

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.


Assuntos
Predisposição Genética para Doença , Modelos Genéticos , Herança Multifatorial , Neoplasias/epidemiologia , Animais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Medição de Risco/métodos , Fatores de Risco
13.
JNCI Cancer Spectr ; 4(2): pkz106, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32195452

RESUMO

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 (HR1-14y = 0.93, 95% CI = 0.83 to 1.04; HR≥15y = 1.28, 95% CI = 1.06 to 1.55; P trend = .009). In NHSII, results were similar though not statistically significant (HR1-14y = 0.99, 95% CI = 0.82 to 1.21; HR≥15y = 1.41, 95% CI = 0.88 to 2.26; P trend = .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 (HR1-14y = 0.71, 95% CI = 0.51 to 0.98; HR≥15y = 1.69, 95% CI = 1.07 to 2.67; P trend = .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≥15y = 1.19, 95% CI = 0.95 to 1.49), Hodgkin lymphoma (HR≥15y = 1.32, 95% CI = 0.43 to 4.06), and multiple myeloma (HR≥15y = 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.

14.
Am J Hematol ; 95(6): 652-661, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32141627

RESUMO

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.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Suécia/epidemiologia
15.
Int J Cancer ; 147(7): 1823-1830, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32067221

RESUMO

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.


Assuntos
Dieta/efeitos adversos , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Dieta Saudável , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Inquéritos Nutricionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida
16.
Cancer Epidemiol Biomarkers Prev ; 29(5): 1074-1078, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108027

RESUMO

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 (P < 5 × 10-8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 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 (P < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; P = 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.


Assuntos
Leucemia Linfocítica Crônica de Células B/epidemiologia , Metabolismo dos Lipídeos/genética , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma Folicular/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Causalidade , Colesterol/sangue , Colesterol/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Linfoma de Zona Marginal Tipo Células B/sangue , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma Folicular/sangue , Linfoma Folicular/genética , Linfoma Folicular/metabolismo , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Análise da Randomização Mendeliana , Razão de Chances , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Fatores de Risco , Triglicerídeos/sangue , Triglicerídeos/metabolismo
17.
Blood Cancer J ; 10(2): 19, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066732

RESUMO

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.


Assuntos
Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Mieloma Múltiplo/etnologia , Mieloma Múltiplo/terapia , Humanos
18.
Hum Mol Genet ; 29(1): 70-79, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600786

RESUMO

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.


Assuntos
Cromossomos Humanos Par 3/genética , Desequilíbrio de Ligação/genética , Linfoma de Células B/metabolismo , Antígeno B7-2/genética , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Receptores de Superfície Celular/genética
19.
Int J Cancer ; 146(1): 35-43, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30802944

RESUMO

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.


Assuntos
Mieloma Múltiplo/mortalidade , Programa de SEER , Adulto , Idoso de 80 Anos ou mais , Causas de Morte , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Porto Rico/epidemiologia , Estados Unidos/epidemiologia
20.
Pharmacoepidemiol Drug Saf ; 29(1): 69-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31736189

RESUMO

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.


Assuntos
Algoritmos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Mieloma Múltiplo/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/urina , Valor Preditivo dos Testes
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