Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nehodgkinský lymfom * genetika   MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• zárodečné buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

BACKGROUND: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non-Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes. METHODS: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell-mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression. RESULTS: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08-1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59-2.07; P-trend (Ptrend) < 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell-mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction. CONCLUSIONS: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions. IMPACT: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.

• MeSH
• autoimunitní nemoci * epidemiologie   genetika   MeSH
• B-lymfocyty MeSH
• celogenomová asociační studie MeSH
• difúzní velkobuněčný B-lymfom * epidemiologie   genetika   MeSH
• folikulární lymfom * epidemiologie   genetika   MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Smoking is a substantial cause of premature death in patients with tuberculosis (TB), particularly in low- and middle-income countries (LMICs) with high TB prevalence. The importance of incorporating smoking cessation and tobacco-dependence treatment (TDT) into TB care is highlighted in the most recent TB care guidelines. Our objective is to identify the likely key facilitators of and barriers to smoking cessation for patients with TB in LMICs. METHODS: A systematic search of studies with English-language abstracts published between January 2000 and May 2019 was undertaken in the EMBASE, MEDLINE, EBSCO, ProQuest, Cochrane and Web of Science databases. Data extraction was followed by study-quality assessment and a descriptive and narrative synthesis of findings. RESULTS: Out of 267 potentially eligible articles, 36 satisfied the inclusion criteria. Methodological quality of non-randomized studies was variable; low risk of bias was assessed in most randomized controlled studies. Identified facilitators included brief, repeated interventions, personalized behavioural counselling, offer of pharmacotherapy, smoke-free homes and a reasonable awareness of smoking-associated risks. Barriers included craving for a cigarette, low level of education, unemployment, easy access to tobacco in the hospital setting, lack of knowledge about quit strategies, and limited space and privacy at the clinics. Findings show that the risk of smoking relapse could be reduced through consistent follow-up upon completion of TB therapy and receiving a disease-specific smoking cessation message. CONCLUSIONS: Raising awareness of smoking-related health risks in patients with TB and implementing guideline-recommended standardized TDT within national TB programmes could increase smoking cessation rates in this high-risk population.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 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.

• Publikační typ
• časopisecké články MeSH

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 (P 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.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.

• MeSH
• celogenomová asociační studie metody   MeSH
• genetická heterogenita MeSH
• heterozygot MeSH
• histokompatibilita - antigeny třídy I genetika   MeSH
• histokompatibilita - antigeny třídy II genetika   MeSH
• lidé MeSH
• nehodgkinský lymfom genetika   MeSH
• prospektivní studie MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

BACKGROUND: Falls are a common complication of advancing Parkinson's disease (PD). Although numerous risk factors are known, reliable predictors of future falls are still lacking. The objective of this prospective study was to investigate clinical and instrumented tests of balance and gait in both OFF and ON medication states and to verify their utility in the prediction of future falls in PD patients. METHODS: Forty-five patients with idiopathic PD were examined in defined OFF and ON medication states within one examination day including PD-specific clinical tests, instrumented Timed Up and Go test (iTUG) and computerized dynamic posturography. The same gait and balance tests were performed in 22 control subjects of comparable age and sex. Participants were then followed-up for 6 months using monthly fall diaries and phone calls. RESULTS: During the follow-up period, 27/45 PD patients and 4/22 control subjects fell one or more times. Previous falls, fear of falling, more severe motor impairment in the OFF state, higher PD stage, more pronounced depressive symptoms, higher daily levodopa dose and stride time variability in the OFF state were significant risk factors for future falls in PD patients. Increased stride time variability in the OFF state in combination with faster walking cadence appears to be the most significant predictor of future falls, superior to clinical predictors. CONCLUSION: Incorporating instrumented gait measures into the baseline assessment battery as well as accounting for both OFF and ON medication states might improve future fall prediction in PD patients. However, instrumented testing in the OFF state is not routinely performed in clinical practice and has not been used in the development of fall prevention programs in PD. New assessment methods for daylong monitoring of gait, balance and falls are thus required to more effectively address the risk of falling in PD patients.

• MeSH
• chůze (způsob) účinky léků   fyziologie   MeSH
• chůze fyziologie   MeSH
• levodopa terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc farmakoterapie   patofyziologie   MeSH
• posturální rovnováha účinky léků   fyziologie   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• strach fyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• úrazy pádem prevence a kontrola   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH