Obesity As a Risk Factor for Acute Promyelocytic Leukemia. Results from Population and Case-Control Studies Across Western Countries and Correlation with Gene Expression in the TCGA

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 448-448 ◽  
Author(s):  
Luca Mazzarella ◽  
Edoardo Botteri ◽  
Anthony Matthews ◽  
Davide Disalvatore ◽  
Vincenzo Bagnardi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factor ◽  
Acute Promyelocytic Leukemia ◽  
Population Based ◽  
Case Control ◽  
Promyelocytic Leukemia ◽  
Transcriptional Analysis ◽  
Clinical Practice Research Datalink ◽  
Case Control Studies ◽  
Increased Risk

Abstract Background. Much uncertainty remains over the aetiology of Acute Myeloid Leukemia (AML) and of its biological subtypes, of which Acute Promyelocytic Leukemia (APL) is the best defined. In recent years, an elevated Body Mass Index (BMI) has been identified as a risk factor for several diseases. Whether BMI influences risk of developing AML and APL is not well understood. Methods. We have collated information from population-based and case-control studies conducted in four different countries. In the population-based study, we obtained data from the Clinical Practice Research Datalink, that includes primary care data of 5.2 million UK citizens. We identified APL and other leukemia cases using ICD identifiers ("APL" (n=24), "non APL-AML" (n=972), lymphoid leukemias ("LL", n=2724) and "other" (n=1850). We fitted linear models to investigate the association between BMI and any of the above leukemic classes. In the case-control studies, we analysed data from patients included in the PETHEMA (Spain, n=414) and GIMEMA (Italy, n=134) databases and patients from the USA-based AML genome sequencing study (the AML TCGA cohort with 22 additional cases characterized at Washington University-St Louis, n=42) ("case" cohorts). We then created age-, gender, ethnicity- and year of diagnosis-matched control cohorts from national BMI surveys and tested deviation of observed cases from expected controls. Lastly, we applied Quantitative Set Analysis for Gene Expression (quSAGE) analysis to investigate APL- or BMI-specific gene expression signatures from TCGA data Findings. In the UK population study, the Hazard Ratio per each 5 kg/m2 increase was 1.44 for APL (95% CI 1.0-2.08), 1.17 for non APL-AML (95% CI 1.10-1.26), 1.04 for LL (95% CI 1.0-1.09) and 1.10 for other leukemias (95% CI 1.04-1.15). In the case-control studies, BMI distribution in cases was significantly higher than expected from controls for all three cohorts: (Italy p<0.001, Spain p=0.011, USA p<0.001). quSAGE transcriptional analysis revealed significant enrichment of several pathways in APL vs other AMLs, in particular arachidonic and linoleic acid metabolism and upregulation of Insulin and IGF1 receptors. Interpretation. A higher BMI was associated with increased risk of leukemia, particularly APL; increased risk of APL was confirmed in all populations examined, irrespective of gender or ethnicity. Elevated BMI should be considered a risk factor for APL development. APL is associated with a characteristic metabolic transcriptional signature that might be responsible for some of its clinical features Disclosures Breccia: Novartis: Consultancy, Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Ariad: Honoraria; Bristol Myers Squibb: Honoraria. Lo Coco:Lundbeck: Honoraria, Speakers Bureau; Novartis: Consultancy; Baxalta: Consultancy; Pfizer: Consultancy; Teva: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1378
Author(s):  
Tú Nguyen-Dumont ◽  
James G. Dowty ◽  
Jason A. Steen ◽  
Anne-Laure Renault ◽  
Fleur Hammet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Risk ◽  
Population Based ◽  
Case Control ◽  
Cancer Information ◽  
Case Control Studies ◽  
Breast Cancer Family ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Control Family

Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5–9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02–11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5–12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11–30%) and 33% (95% CI 21–48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.

scholarly journals Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies

Thorax ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Christos V Chalitsios ◽  
Dominick E Shaw ◽  
Tricia M McKeever
Keyword(s):  
Cumulative Dose ◽  
Inhaled Corticosteroids ◽  
Conditional Logistic Regression ◽  
Fragility Fractures ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Case Control Studies ◽  
Increased Risk ◽  
Nested Case Control

BackgroundInhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established.MethodsWe conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated.ResultsThere was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively.ConclusionsThe findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.

scholarly journals Antihypertensive Medications and COVID-19 Diagnosis and Mortality: Population-based Case-Control Analysis in the United Kingdom

2020 ◽  
Author(s):  
Emma Rezel-Potts ◽  
Abdel Douiri ◽  
Phil J Chowienczyk ◽  
Martin C Gulliford
Keyword(s):  
Antihypertensive Therapy ◽  
Population Based ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Control Analysis ◽  
Antihypertensive Medications ◽  
Lower Odds ◽  
Healthcare Seeking ◽  
Increased Risk

Objectives: To evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare seeking behaviour. Design: A population-based case control study with additional cohort analysis. Setting: Primary care patients from the UK Clinical Practice Research Datalink (CPRD). Participants: 16 866 patients with COVID-19 events in the CPRD from 29th January to June 25th 2020 and 70 137 matched controls. Main outcome measures: We explored associations between COVID-19 diagnosis and prescriptions for angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). We evaluated all-cause mortality among COVID-19 cases. Analyses were adjusted for covariates and consultation frequency. Results: In covariate adjusted analyses, ACEIs were associated with lower odds of COVID-19 diagnosis (0.82, 95% confidence interval 0.77 to 0.88) as were ARBs, 0.87 (0.80 to 0.95) with little attenuation from adjustment for consultation frequency. In fully adjusted analyses, C and D were also associated with lower odds of COVID-19. Increased odds of COVID-19 for B (1.19, 1.12 to 1.26), were attenuated after adjustment for consultation frequency (1.01, 0.95 to 1.08). In adjusted analyses, patients treated with ACEIs or ARBs had similar mortality to patients treated with classes B, C, D or O (1.00, 0.83 to 1.20) or patients receiving no antihypertensive therapy (0.99, 0.83 to 1.18). Conclusions: Associations were sensitive to adjustment for confounding and healthcare seeking, but there was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.

scholarly journals Population-based estimates of the age-specific cumulative risk of breast cancer for pathogenic variants in CHEK2: Findings from the Australian Breast Cancer Family Registry.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 551-551
Author(s):  
Tu Nguyen-Dumont ◽  
James Dowty ◽  
Jason A Steen ◽  
Anne-Laure Renault ◽  
Fleur Hammet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Risk ◽  
Population Based ◽  
Case Control ◽  
Cancer Information ◽  
Case Control Studies ◽  
Breast Cancer Family ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Control Family

551 Background: Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein truncating variant CHEK2c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. Methods: We conducted a genetic screen of CHEK2 in an Australian population-based case-control-family study of breast cancer. This study is focused on disease at an early age and participants were unselected for family history. The age-specific cumulative risk (penetrance) of breast cancer was estimated using segregation analysis. Results: The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5-9.5; p < 0.0001) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02-11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5-12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11-30%) and 33% (95% CI 21-48%) to age 60 and 80 years, respectively. Conclusions: These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.

scholarly journals Association of interleukin 10 rs1800896 polymorphism with susceptibility to breast cancer: a meta-analysis

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052090486 ◽  
Author(s):  
ZiYin Zhu ◽  
Ji-Bin Liu ◽  
Xi Liu ◽  
LinXue Qian
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Interleukin 10 ◽  
Population Based ◽  
Case Control ◽  
Recessive Model ◽  
Breast Cancers ◽  
Case Control Studies ◽  
Asian Populations ◽  
Increased Risk

Objective To evaluate the correlation between interleukin 10 (IL-10) −1082A/G polymorphism (rs1800896) and breast cancers by performing a meta-analysis. Methods The Embase and Medline databases were searched through 1 September 2018 to identify qualified articles. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were applied to evaluate associations. Results In total, 14 case-control studies, including 5320 cases and 5727 controls, were analyzed. We detected significant associations between the IL10 −1082 G/G genotype and risk of breast cancer (AA + AG vs. GG: OR = 0.88, 95% CI = 0.80–0.97). Subgroup analyses confirmed a significant association in Caucasian populations (OR = 0.89, 95% CI = 0.80–0.99), in population-based case-control studies (OR = 0.87, 95% CI = 0.78–0.96), and in studies with ≥500 subjects (OR = 0.88, 95% CI = 0.79–0.99) under the recessive model (AA + AG vs. GG). No associations were found in Asian populations. Conclusions The IL10 −1082A/G polymorphism is associated with an increased risk of breast cancer. The association between IL10 −1082 G/G genotype and increased risk of breast cancer is more significant in Caucasians, in population-based studies, and in larger studies.

scholarly journals The Association between PON1 (Q192R and L55M) Gene Polymorphisms and Risk of Cancer: A Meta-Analysis Based on 43 Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaolan Pan ◽  
Lei Huang ◽  
Meiqin Li ◽  
Dan Mo ◽  
Yihua Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Risk ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Population Based ◽  
Case Control ◽  
Cancer Type ◽  
Case Control Studies ◽  
Increased Risk ◽  
Risk Of Cancer

Q192R and L55M polymorphism were considered to be associated with the development of multiple cancers. Nevertheless, the results of these researches were inconclusive and controversial. Therefore, we conducted a meta-analysis of all eligible case-control studies to assess the association between PON1 (Q192R and L55M) gene polymorphisms and risk of cancer. With the STATA 14.0 software, we evaluated the strength of the association by using the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 43 case-control publications 19887 cases and 23842 controls were employed in our study. In all genetic models, a significant association between PON1-L55M polymorphisms and overall cancer risk was observed. Moreover, in the stratified analyses by cancer type, polymorphism of PON1-L55M played a risk factor in the occurrence of breast cancer, hematologic cancer, and prostate cancer. Similarly, an increased risk was observed in the Caucasian and Asian population as well as hospital-based group and population-based group. For PON1-Q192R polymorphisms, in the stratified analyses by cancer type, PON1-Q192R allele was associated with reduced cancer risks in breast cancer. Furthermore, for racial stratification, there was a reduced risk of cancer in recession model in Caucasian population. Similarly, in the stratification analysis of control source, the overall risk of cancer was reduced in the heterozygote comparison and dominant model in the population-based group. In conclusion, PON1-Q192R allele decreased the cancer risk especially breast cancer; there was an association between PON1-L55M allele and increased overall cancer risk. However, we need a larger sample size, well-designed in future and at protein levels to confirm these findings.

scholarly journals 1235Household air pollution and lung cancer mortality among never-smokers: findings from the China Kadoorie Biobank

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Elvin Cheng ◽  
Ka Hung Chan ◽  
Marianne Weber ◽  
Julia Steinberg ◽  
Karen Canfell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Air Pollution ◽  
Risk Factor ◽  
Cox Regression ◽  
Total Duration ◽  
Case Control ◽  
Mortality Data ◽  
Case Control Studies ◽  
Increased Risk ◽  
Never Smokers

Abstract Background Household air pollution (HAP) has been classified as a major risk factor for lung cancer (LC) among never-smokers, however, evidence is largely from case-control studies. Using the prospective cohort China Kadoorie Biobank (CKB), we investigated the association of HAP with LC death among never-smokers. Methods The CKB, a large-scale cohort study, recruited 512,715 adults aged 30–79 years from ten regions in China during 2004-2008. Self-reported never-smoking participants were followed up to 31/12/2016 with linkage to mortality data. Total duration of HAP exposure was calculated from self-reported solid fuel use in domestic cooking and slow-burning stoves in participants’ three most recent residences, and self-reported coal-smoky home in winter during their lifetime. Hazard ratios (HR) and 95% confidence intervals (CI) of LC death associated with HAP exposure were estimated using Cox regression, adjusting for key confounders including several demographic, environmental and lifestyle factors. Results There were 979 LC deaths among 323,794 never-smokers without prior cancer during a median follow-up of 10.2 years. There was a log-linear positive association between HAP exposure and LC death (p-trend=0.0034), with 4% increased risk per 5-year longer exposure (HR = 1.04; 95% CI 1.01-1.06); and participants with 40.1-50.0 years of exposure had the highest risk compared to the never-exposed (HR = 1.53; 95% CI 1.13-2.07). Conclusions This study provides new prospective evidence that HAP exposure is associated with LC death among Chinese never-smokers, and strengthens the previous evidence largely based on case-control studies. Key messages This study supports HAP as an important risk factor for LC development among never-smokers.

scholarly journals Relevance of hMLH1 -93G>A, 655A>G and 1151T>A polymorphisms with colorectal cancer susceptibility: a meta-analysis based on 38 case-control studies

2018 ◽  
Vol 64 (10) ◽  
pp. 942-951 ◽  
Author(s):  
Mohammad Zare ◽  
Jamal Jafari-Nedooshan ◽  
Mohammadali Jafari ◽  
Hossein Neamatzadeh ◽  
Seyed Mojtaba Abolbaghaei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Asian Population ◽  
Case Control ◽  
Biomedical Literature ◽  
Case Control Studies ◽  
Increased Risk ◽  
Comprehensive Search ◽  
Meta Analyses

SUMMARY OBJECTIVE: There has been increasing interest in the study of the association between human mutL homolog 1 (hMLH1) gene polymorphisms and risk of colorectal cancer (CRC). However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this gene. METHODS: A comprehensive search was conducted in the PubMed, EMBASE, Chinese Biomedical Literature databases until January 1, 2018. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. RESULTS: Finally, 38 case-control studies in 32 publications were identified met our inclusion criteria. There were 14 studies with 20668 cases and 19533 controls on hMLH1 −93G>A, 11 studies with 5,786 cases and 8,867 controls on 655A>G and 5 studies with 1409 cases and 1637 controls on 1151T>A polymorphism. The combined results showed that 655A>G and 1151T>A polymorphisms were significantly associated with CRC risk, whereas −93G>A polymorphism was not significantly associated with CRC risk. As for ethnicity, −93G>A and 655A>G polymorphisms were associated with increased risk of CRC among Asians, but not among Caucasians. More interestingly, subgroup analysis indicated that 655A>G might raise CRC risk in PCR-RFLP and HB subgroups. CONCLUSION: Inconsistent with previous meta-analyses, this meta-analysis shows that the hMLH1 655A>G and 1151T>A polymorphisms might be risk factors for CRC. Moreover, the −93G>A polymorphism is associated with the susceptibility of CRC in Asian population.

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