Publications by authors named "Eleanor Kane"

51 Publications

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.

J Transl Genet Genom 2021 17;5:200-217. Epub 2021 Jun 17.

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

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 (β = 21.1, SE = 4.41, = 1.6 × 10) and FL (β = 11.4, SE = 5.82, = 0.02) but not DLBCL ( = 1.0) or MZL ( = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, = 2.4 × 10). 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20517/jtgg.2021.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494431PMC
June 2021

Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL): findings from a UK population-based cohort.

BMJ Open 2021 02 22;11(2):e041296. Epub 2021 Feb 22.

Department of Health Sciences, University of York, York, UK

Objective: To examine mortality and morbidity patterns before and after premalignancy diagnosis in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) and compare their secondary healthcare activity to that of the general population.

Design: Population-based patient cohort, within which each patient is matched at diagnosis to 10 age-matched and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations and Hospital Episode Statistics.

Setting: The UK's Haematological Malignancy Research Network, which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory.

Participants: All patients newly diagnosed during 2009-2015 with MGUS (n=2193) or MBL (n=561) and their age and sex-matched comparators (n=27 538).

Main Outcome Measures: Mortality and hospital inpatient and outpatient activity in the 5 years before and 3 years after diagnosis.

Results: Individuals with MGUS experienced excess morbidity in the 5 years before diagnosis and excess mortality and morbidity in the 3 years after diagnosis. Increased rate ratios (RRs) were evident for nearly all clinical specialties, the largest, both before and after diagnosis, being for nephrology (before RR=4.29, 95% CI 3.90 to 4.71; after RR=13.8, 95% CI 12.8 to 15.0) and rheumatology (before RR=3.40, 95% CI 3.18 to 3.63; after RR=5.44, 95% CI 5.08 to 5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL.

Conclusions: MGUS and MBL are generally considered to be relatively benign, since most individuals with monoclonal immunoglobulins never develop a B-cell malignancy or any other monoclonal protein-related organ/tissue-related disorder. Nonetheless, our findings offer strong support for the view that in some individuals, monoclonal gammopathy has the potential to cause systemic disease resulting in wide-ranging organ/tissue damage and excess mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-041296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903106PMC
February 2021

Correction to: Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study.

Cancer Causes Control 2020 06;31(6):607

Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Unfortunately, the word "Group" is missed in the article title of the original publication. It has been corrected by this erratum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01297-xDOI Listing
June 2020

Age-, sex- and disease subtype-related foetal growth differentials in childhood acute myeloid leukaemia risk: A Childhood Leukemia International Consortium analysis.

Eur J Cancer 2020 05 9;130:1-11. Epub 2020 Mar 9.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. Electronic address:

Aim: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases.

Methods: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed.

Results: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers.

Conclusions: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.01.018DOI Listing
May 2020

Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study.

Cancer Causes Control 2020 05 2;31(5):451-462. Epub 2020 Mar 2.

Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Purpose: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis.

Methods: A total of 7,926 NHL patients and 10,018 controls from 12 case-control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. P was used to account for multiple comparisons.

Results: There was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (p = 0.04, OR = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (p = 0.03, OR = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes.

Conclusions: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01266-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534692PMC
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196490PMC
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Palliative care for non-cancer conditions in primary care: a time trend analysis in the UK (2009-2014).

BMJ Support Palliat Care 2020 Jan 13. Epub 2020 Jan 13.

Department of Health Sciences, University of York and Hull York Medical School, York, UK.

Objectives: While guidelines recommend palliative care in non-cancer conditions, this has not been widely implemented. We examined whether the recording of a palliative care approach and the numbers of hospital deaths for deceased patients with heart failure, dementia, chronic obstructive pulmonary disease (COPD) and cancer have changed since the UK End-of-Life Care Strategy was introduced.

Methods: We conducted sequential cross-sectional studies of decedents within the UK's Clinical Practice Research Datalink and Hospital Episode Statistics. All adults with a primary care record of COPD (n=5426), dementia (n=7339), heart failure (n=6409) or cancer (n=18 668) who died during three 1 year periods (April 2009 to March 2014) were included. Evidence of a palliative care approach was identified from primary care records, and death in hospital from secondary care data.

Results: From 2009 to 2014, proportions with a primary care record of palliative care increased for COPD from 13.6% to 21.2%; dementia from 20.9% to 40.7%; and heart failure from 12.6% to 21.2%; but remained substantially lower than for cancer (57.6% to 61.9%). Median days before death of recording improved for COPD (145 to 224) and dementia (44 to 209); but not for heart failure (168.5 to 153) and cancer (123 to 114). Trends in hospital deaths were not consistently downward, although the proportions of patients dying in hospital were lower in the last period compared with the first.

Conclusions: Recording of a palliative care approach for non-cancer conditions has increased since the introduction of the UK End-of-Life Care Strategy, but remains inadequate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjspcare-2019-001833DOI Listing
January 2020

Hodgkin lymphoma detection and survival: findings from the Haematological Malignancy Research Network.

BJGP Open 2019 Dec 10. Epub 2019 Dec 10.

Reader, Epidemiology & Cancer Statistics Group (ECSG), Department of Health Sciences, University of York, York, UK.

Background: Hodgkin lymphoma is usually detected in primary care with early signs and symptoms, and is highly treatable with standardised chemotherapy. However, late presentation is associated with poorer outcomes.

Aim: To investigate the relationship between markers of advanced disease, emergency admission, and survival following a diagnosis of classical Hodgkin lymphoma (CHL).

Design & Setting: The study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths.

Method: All 971 patients with CHL newly diagnosed between 1 September 2004-31 August 2015 were followed until 18th December 2018.

Results: The median diagnostic age was 41.5 years (range 0-96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate-high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged <25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% [95% confidence interval {CI} = 60.3 to 75.2] versus 89.8% [95% CI = 87.0 to 92.0], respectively [<0.01]). However, after adjusting for clinically important prognostic factors, no difference in survival remained.

Conclusion: These findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3399/bjgpopen19X101668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995857PMC
December 2019

Risk of mature B-cell neoplasms and precursor conditions after joint replacement: A report from the Haematological Malignancy Research Network.

Int J Cancer 2020 08 23;147(3):702-708. Epub 2019 Nov 23.

Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, United Kingdom.

Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n = 1,763), diffuse large B-cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B-cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1-1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1-1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2-2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0-1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2-1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3-5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0-3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0-1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317514PMC
August 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019

Blood transfusion history and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

Cancer Causes Control 2019 Aug 4;30(8):889-900. Epub 2019 Jun 4.

Dept of Epidemiology and Biostatistics, University of California San Francisco, 3333 California Street, Suite 280, San Francisco, CA, 94118, USA.

Purpose: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL).

Methods: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables.

Results: Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65-0.83) but not women (OR 0.92; 95% CI 0.83-1.03), p = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45-0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72-0.98) studies.

Conclusions: In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-019-01188-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613988PMC
August 2019

The impact of rheumatological disorders on lymphomas and myeloma: a report on risk and survival from the UK's population-based Haematological Malignancy Research Network.

Cancer Epidemiol 2019 04 4;59:236-243. Epub 2019 Mar 4.

Department of Health Sciences, University of York, York, UK.

Background: Autoimmune inflammatory disease increases the risk of diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), but findings for other mature B-cell malignancies are equivocal. Furthermore, it has been suggested that the increase in DLBCL is due to the activated B-cell (ABC) subtype; but data on this, and the impact of inflammatory co-morbidities on survival, are sparse and contradictory.

Methods: Data are from an established UK population-based cohort. Patients (n = 6834) diagnosed between 01/2009 and 08/2015 are included; DLBCL (n = 1771), myeloma (n = 1760), chronic lymphocytic leukaemia (CLL, n = 1580), MZL (n = 936), and follicular lymphoma (FL, n = 787). Information on rheumatological disorders and deaths was obtained by record-linkage to nationally compiled Hospital Episode Statistics, with age-and sex-matched individuals (n = 68,340) from the same catchment population (˜4 million people) providing the comparator.

Results: Significantly increased risks for DLBCL (OR = 2.3, 95% CI 1.8-2.8) and MZL (OR = 2.0, 95% CI 1.5-2.7) were found for those with rheumatological disorders; the site distribution of those with/without rheumatological conditions differing for DLBCL (p = 0.007) and MZL (p = 0.002). No increases in risk were observed for the remaining mature B-cell malignancies, and no associations with survival were detected for DLBCL (age-adjusted HR = 1.2, 95% CI 0.9-1.6) or MZL (age-adjusted HR = 1.0, 95% CI 0.6-1.9). Furthermore, whilst our findings provide evidence for an association with rheumatological disease severity for DLBCL, they offer little support for the notion that the association is driven by an increase in the incidence of the ABC subtype.

Conclusion: Our findings support the hypothesis that the chronic activation and proliferation of specific B-cell populations which characterize autoimmune disease increase the potential for the lymphomagenic events that lead to DLBCL and MZL in both males and females; but have no impact on the development of CLL, FL or MM, or on survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canep.2019.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452783PMC
April 2019

Parental age and the risk of childhood acute myeloid leukemia: results from the Childhood Leukemia International Consortium.

Cancer Epidemiol 2019 04 15;59:158-165. Epub 2019 Feb 15.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. Electronic address:

Background: Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent.

Aim: To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies.

Material/methods: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants <1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period.

Results: Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers ≥40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year.

Conclusions: An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canep.2019.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098424PMC
April 2019

Author Correction: Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.

Nat Commun 2019 01 8;10(1):157. Epub 2019 Jan 8.

MRC University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, UK.

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-08105-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325156PMC
January 2019

Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium.

Eur J Epidemiol 2018 Oct 14;33(10):965-976. Epub 2018 May 14.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (OR 1.05, 95% CI 1.00-1.11; OR 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (OR 0.99, 95% CI 0.91-1.07, heterogeneity I = 58%, p = 0.002; OR 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-018-0402-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384148PMC
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. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-17-2900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065509PMC
July 2018

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.

Lupus Sci Med 2017 12;4(1):e000187. Epub 2017 Nov 12.

Department of Health Sciences, University of York, York, UK.

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis.

Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765.

Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2016-000187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715504PMC
November 2017

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.

Nat Commun 2017 12 1;8(1):1892. Epub 2017 Dec 1.

MRC University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, UK.

Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10), 6q23.3 (rs6928977, P = 4.62 × 10), 10p14 (rs3781093, P = 9.49 × 10), 13q34 (rs112998813, P = 4.58 × 10) and 16p13.13 (rs34972832, P = 2.12 × 10). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-017-00320-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711884PMC
December 2017

Emergency admission and survival from aggressive non-Hodgkin lymphoma: A report from the UK's population-based Haematological Malignancy Research Network.

Eur J Cancer 2017 06 13;78:53-60. Epub 2017 Apr 13.

Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.

Background: Non-Hodgkin lymphoma (NHL) is often diagnosed after emergency presentation, a route associated with poor survival and an indicator of diagnostic delay. Accounting for around half of all NHLs, diffuse large B-cell lymphoma (DLBCL) is of particular interest since although it is potentially curable with standardised chemotherapy it can be challenging to identify at an early stage in the primary care setting.

Patients And Methods: Set within a socio-demographically representative United Kingdom population of around 4 million people, data are from an established patient cohort. This report includes all patients (≥18 years) diagnosed with DLBCL 2004-2011 (n = 1660). Emergency admissions were identified via linkage to Hospital Episode Statistics using standard methods, and survival was examined using proportional hazards regression.

Results: Two out of every five patients were diagnosed following an emergency admission, and this was associated with advanced disease and poor survival (p < 0.001). Among the 80% of patients treated with curative chemotherapy, survival discrepancies emerged at the point of diagnosis; the adjusted hazard ratio (emergency versus non-emergency) at one month being 4.0 (95% confidence interval 1.9-8.2). No lasting impact was evident in patients who survived for 12 months or more.

Conclusion: Emergency presentation impacts negatively on DLBCL survival; patients presenting via this route have significantly poorer outcomes than patients with similar clinical characteristics who present via other routes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2017.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446261PMC
June 2017

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.

Hum Mol Genet 2016 Apr 9;25(8):1663-76. Epub 2016 Feb 9.

Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddw027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854019PMC
April 2016

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

J Natl Cancer Inst 2015 Dec 12;107(12):djv279. Epub 2015 Oct 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (JNS, OP, SIB, QL, CCA, LTA, JDF, MTL, LM, SAS, PRT, KAM, PR, DA, DB, BAB, AB, LBr, WHC, CCC, JSC, JFFJr, NDF, LEBF, MGC, AMG, RNH, NH, WH, PDI, BTJ, CK, CMK, LML, MSL, LEM, LPO, RSSS, WeiT, MT, CWa, SW, NW, KY, PH, LMM, NEC, NR, DTS, SJC, NC); Information Management Services, Silver Spring, MD (WAW, CG); Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD (MY, ZW, LBu, AH, CLi); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (IDV, KAB, BMB, CoC, MCB, CF, EG, SL, JP, MSt, DJH); Department of Epidemiology, Harvard School of Public Health, Boston, MA (IDV, OA, KAB, CoC, MCB, EG, RSK, SL, JP, HDS, MSt, DTr, DJH, PK); Ontario Health Study, Toronto, Ontario, Canada (MPP); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (HOA, EWe); Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (AA, MF); UCL Cancer Institute, London, UK (MFA, AMF, DH); Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK (MFA, AMF, DH, RT); Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China (SJA, JS, YLW, XCZ); Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden (UA, RH, BSM); Division of Urologic Surgery, Washington University School of Medicine, Saint Louis, MO (GAJr, RGIII); Litwin Centre for Cancer Genetics, University of Toronto, Ontario, Canada (ILA, NG, JSW); Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (ILA, SG, NG, JSW); Hematology Unit, Ospedale Oncologico di Riferimento Regionale A. Businco, Cagliari, Italy (EA); Department of Medicin

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.

Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.

Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djv279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806328PMC
December 2015

Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium.

Environ Health Perspect 2016 Apr 4;124(4):396-405. Epub 2015 Sep 4.

Centre for Public Health Research, Massey University, Wellington Campus, Wellington, New Zealand.

Background: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies.

Objectives: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest.

Methods: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL).

Results: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women's hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women's hairdressers and for DLBCL and PTCL in textile workers.

Conclusions: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry-related exposures may contribute to NHL risk. Associations with women's hairdresser and textile occupations may be specific for certain NHL subtypes.

Citation: 't Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G, Fritschi L, Brennan P, Foretova L, Maynadié M, Becker N, Nieters A, Staines A, Campagna M, Chiu B, Clavel J, de Sanjose S, Hartge P, Holly EA, Bracci P, Linet MS, Monnereau A, Orsi L, Purdue MP, Rothman N, Lan Q, Kane E, Seniori Costantini A, Miligi L, Spinelli JJ, Zheng T, Cocco P, Kricker A. 2016. Occupation and risk of non-Hodgkin lymphoma and its subtypes: a pooled analysis from the InterLymph Consortium. Environ Health Perspect 124:396-405; http://dx.doi.org/10.1289/ehp.1409294.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/ehp.1409294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829988PMC
April 2016

Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium.

Cancer Epidemiol Biomarkers Prev 2015 Jul 11;24(7):1061-70. Epub 2015 May 11.

Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom.

Background: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.

Method: Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).

Results: Obesity (BMI ≥ 30 kg/m(2)) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02-1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27-2.94), with a RERI of 0.41 (95% CI, -0.05-0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.

Conclusions: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.

Impact: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-14-1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490950PMC
July 2015

Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci.

Am J Epidemiol 2015 Mar 23;181(6):406-21. Epub 2015 Feb 23.

Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwu290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402340PMC
March 2015

A genome-wide association study of marginal zone lymphoma shows association to the HLA region.

Nat Commun 2015 Jan 8;6:5751. Epub 2015 Jan 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms6751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287989PMC
January 2015

Palliative care among heart failure patients in primary care: a comparison to cancer patients using English family practice data.

PLoS One 2014 25;9(11):e113188. Epub 2014 Nov 25.

Palliative Medicine, Hull York Medical School, University of Hull, Hull, East Yorkshire, United Kingdom.

Introduction: Patients with heart failure have a significant symptom burden and other palliative care needs often over a longer period than patients with cancer. It is acknowledged that this need may be unmet but by how much has not been quantified in primary care data at the population level.

Methods: This was the first use of Clinical Practice Research Datalink, the world's largest primary care database to explore recognition of the need for palliative care. Heart failure and cancer patients who had died in 2009 aged 18 or over and had at least one year of primary care records were identified. A palliative approach to care among patients with heart failure was compared to that among patients with cancer using entry onto a palliative care register as a marker for a palliative approach to care.

Results: Among patients with heart failure, 7% (234/3 122) were entered on the palliative care register compared to 48% (3 669/7 608) of cancer patients. Of heart failure patients on the palliative care register, 29% (69/234) were entered onto the register within a week of their death.

Conclusions: This confirms that the stark inequity in recognition of palliative care needs for people with heart failure in a large primary care dataset. We recommend a move away from prognosis based criteria for palliative care towards a patient centred approach, with assessment of and attention to palliative needs including advance care planning throughout the disease trajectory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113188PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244094PMC
August 2015

Germ-line transmitted, chromosomally integrated HHV-6 and classical Hodgkin lymphoma.

PLoS One 2014 10;9(11):e112642. Epub 2014 Nov 10.

MRC - University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.

A unique feature of both human herpesvirus 6A and B (HHV-6A and B) among human herpesviruses is their ability to integrate into chromosomal telomeres. In some individuals integrated viral genomes are present in the germ-line and result in the vertical transmission of HHV-6; however, little is known about the disease associations of germ-line transmitted, chromosomally integrated HHV-6 (ciHHV-6). Recent publications suggest that HHV-6 is associated with classical Hodgkin lymphoma (cHL). Here we examine the prevalence of ciHHV-6 in 936 cases of cHL and 563 controls by screening with a duplex TaqMan assay and confirming with droplet digital PCR. ciHHV-6 was detected in 10/563 (1.8%) controls and in all but one individual the virus was HHV-6B. Amongst cases 16/936 (1.7%) harboured ciHHV-6, thus demonstrating no association between ciHHV-6 and risk of cHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112642PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226568PMC
December 2015

Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.

Am J Hum Genet 2014 Oct;95(4):462-71

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

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2014.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185120PMC
October 2014

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.

Nat Genet 2014 Nov 28;46(11):1233-8. Epub 2014 Sep 28.

1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Medical Research Council (MRC)-Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213349PMC
November 2014
-->