ORCID Profile
0000-0001-9161-1357
Current Organisation
Dubllin City University
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Publications
Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium
Publisher: Environmental Health Perspectives
Date: 04-2016
DOI: 10.1289/EHP.1409294
Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes
Publisher: American Society of Hematology
Date: 15-04-2008
DOI: 10.1182/BLOOD-2007-10-119974
Abstract: Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.
A genome-wide association study of marginal zone lymphoma shows association to the HLA region
Publisher: Springer Science and Business Media LLC
Date: 08-01-2015
DOI: 10.1038/NCOMMS6751
Abstract: Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P =3.95 × 10 −15 ) and HLA-B (rs2922994, P =2.43 × 10 −9 ) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Publisher: Springer Science and Business Media LLC
Date: 09-03-2016
DOI: 10.1038/NCOMMS10933
Abstract: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES , P =2.55 × 10 −11 ), 6p25.2 (rs73718779, SERPINB6 , P =1.97 × 10 −8 ) and 3q28 (rs9815073, LPP , P =3.62 × 10 −8 ), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11 , P =1.00 × 10 −11 ) in the combined analysis. We find suggestive evidence ( P × 10 −7 ) for two additional new loci at 4q24 (rs10028805, BANK1 , P =7.19 × 10 −8 ) and 3p22.2 (rs1274963, CSRNP1 , P =2.12 × 10 −7 ). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
COVID-19 incidence and outcome by affluence/deprivation across three pandemic waves in Ireland: A retrospective cohort study using routinely collected data
Publisher: Public Library of Science (PLoS)
Date: 21-07-2023
DOI: 10.1371/JOURNAL.PONE.0287636
Abstract: Since the pandemic onset, deprivation has been seen as a significant determinant of COVID-19 incidence and mortality. This study explores outcomes of COVID-19 in the context of material deprivation across three pandemic waves in Ireland. Between 1st March 2020 and 13th May 2021, 252,637 PCR-confirmed COVID-19 cases were notified in Ireland. Cases were notified to the national Computerised Infectious Disease Reporting (CIDR) system. Each case was geo-referenced and assigned a deprivation category according to the Haase-Pratschke (HP) Deprivation Index. Regression modelling examined three outcomes: admission to hospital admission to an intensive care unit (ICU) and death. Deprivation increased the likelihood of contracting COVID-19 in all age groups and across all pandemic waves, except for the 20–39 age group. Deprivation, age, comorbidity and male gender carried increased risk of hospital admission. Deprivation was not a factor in predicting ICU admission or death, and diagnosis in wave 2 was associated with the lowest risk of all three outcomes. Our study suggests that COVID-19 spreads easily through all strata of society and particularly in the more deprived population however this was not a consistent finding. Ireland is ethnically more homogenous than other countries reporting a larger deprivation gradient, and in such societies, structural racial differences may contribute more to poor COVID outcomes than elements of deprivation.
Neighbourhood characteristics and the incidence of first-episode psychosis and duration of untreated psychosis
Publisher: Cambridge University Press (CUP)
Date: 05-02-2016
DOI: 10.1017/S003329171500286X
Abstract: The incidence of psychotic disorders varies between geographical areas and it has been hypothesized that neighbourhood-level factors may influence this variation. It is also plausible that the duration of untreated psychosis (DUP) is associated with neighbourhood characteristics. The aims of this study were to determine whether the incidence of first-episode psychosis (FEP) and the DUP are associated with the level of social deprivation, fragmentation, social capital and population density. All in iduals with a FEP from a geographical defined catchment area over a 5-year period were included. Age-standardized incidence rates were calculated for each neighbourhood factor. A total of 292 cases of FEP were included in the study and 45% had a diagnosis of a schizophrenia-spectrum disorder. The age standardized incidence rate of FEP in the most deprived area was 72.4 [95% confidence interval (CI) 26.4–162.7] per 100 000 person-years compared with 21.5 (95% CI 17.6–26.0) per 100 000 person-years in the most affluent areas. This represents a 3.4-fold increase in FEP incidence in the most deprived areas. The incidence of FEP was also increased in neighbourhoods that were more socially fragmented [incidence rate ratio (IRR) = 2.40, 95% CI 1.05–5.51, p = 0.04] and there was a trend for the incidence to be increased in neighbourhoods with lower social capital (IRR = 1.43, 95% CI 0.99–2.06, p = 0.05). The median DUP was 4 months and was higher in more socially fragmented neighbourhoods. The incidence of psychotic disorders is related to neighbourhood factors and it may be useful to consider neighbourhood factors when allocating resources for early intervention services.
Birth order and risk of non-hodgkin lymphoma - True association or bias?
Publisher: Oxford University Press (OUP)
Date: 18-08-2010
DOI: 10.1093/AJE/KWQ167
Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project
Publisher: Oxford University Press (OUP)
Date: 08-2014
Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
Publisher: BMJ
Date: 10-2017
Atopic disease and risk of non-Hodgkin lymphoma
Publisher: American Association for Cancer Research (AACR)
Date: 12-08-2009
DOI: 10.1158/0008-5472.CAN-08-4372
Abstract: We performed a pooled analysis of data on atopic disease and risk of non–Hodgkin lymphoma (NHL) from 13 case-control studies, including 13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed 2 years or more before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were computed in two-stage random-effects or joint fixed-effects models, and adjusted for age, sex, and study center. When modeled in idually, lifetime history of asthma, hay fever, specific allergy (excluding hay fever, asthma, and eczema), and food allergy were associated with a significant reduction in NHL risk, and there was no association for eczema. When each atopic condition was included in the same model, reduced NHL risk was only associated with a history of allergy (OR, 0.80 95% CI, 0.68–0.94) and reduced B-cell NHL risk was associated with history of hay fever (OR, 0.85 95% CI, 0.77–0.95) and allergy (OR, 0.84 95% CI, 0.76–0.93). Significant reductions in B-cell NHL risk were also observed in in iduals who were likely to be truly or highly atopic—those with hay fever, allergy, or asthma and at least one other atopic condition over their lifetime. The inverse associations were consistent for the diffuse large B-cell and follicular subtypes. Eczema was positively associated with lymphomas of the skin misdiagnosis of lymphoma as eczema is likely, but progression of eczema to cutaneous lymphoma cannot be excluded. This pooled study shows evidence of a modest but consistent reduction in the risk of B-cell NHL associated with atopy. [Cancer Res 2009 (16):6482–9]
Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
Publisher: Oxford University Press (OUP)
Date: 09-02-2016
DOI: 10.1093/HMG/DDW027
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Publisher: American Association for Cancer Research (AACR)
Date: 15-07-2018
DOI: 10.1158/0008-5472.CAN-17-2900
Abstract: 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 ersity 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 ersity reduces risk for non-Hodgkin lymphoma. Cancer Res 78(14) 4086–96. ©2018 AACR.
Self‐reported history of infections and the risk of non‐Hodgkin lymphoma: An InterLymph pooled analysis
Publisher: Wiley
Date: 12-08-2012
DOI: 10.1002/IJC.27438
Associations of Non-Hodgkin Lymphoma (NHL) Risk With Autoimmune Conditions According to Putative NHL Loci
Publisher: Oxford University Press (OUP)
Date: 23-02-2015
DOI: 10.1093/AJE/KWU290
Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region
Publisher: Elsevier BV
Date: 10-2014
PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium
Publisher: American Society of Hematology
Date: 29-11-2012
DOI: 10.1182/BLOOD-2012-05-427989
Abstract: Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but in idual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10−11), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, P random = 1.07 × 10−9) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes.
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
Publisher: Springer Science and Business Media LLC
Date: 16-06-2013
DOI: 10.1038/NG.2652
Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (Inte
Publisher: American Society of Hematology
Date: 27-12-2006
DOI: 10.1182/BLOOD-2006-06-031948
Abstract: A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for in iduals who reported first-degree relatives with NHL (OR = 1.5 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6 95% CI = 1.1-2.3), and leukemia (OR = 1.4 95% CI = 1.2-2.7). Risk was highest among in iduals who reported a brother with NHL (OR = 2.8 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.
Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
Publisher: Springer Science and Business Media LLC
Date: 28-09-2014
DOI: 10.1038/NG.3105
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