Familial CLL: Genes and Environment

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 339-345 ◽  
Author(s):  
Lynn R. Goldin ◽  
Susan L. Slager
Keyword(s):  
B Cell ◽  
Large Scale ◽  
Familial Aggregation ◽  
Association Studies ◽  
Large Population ◽  
Gene Mutations ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Genes And Environment ◽  
The U.S

Abstract Families with multiple individuals affected with chronic lymphocytic leukemia (CLL) and other related B-cell tumors have been described in the literature. Familial CLL does not appear to differ from sporadic CLL in terms of prognostic markers and clinical outcome. While some environmental factors (such as farming-related exposures and occupational chemicals) may increase risk of CLL, results of epidemiologic studies have been generally inconsistent. Rates of CLL in the population show significant international variation, with the highest rates in the U.S. and Europe and the lowest rates in Asia. Migrants from Asia to the U.S. also have low rates of CLL, which supports a greater role for genetic compared with environmental risk factors. Large, population-based case-control and cohort studies have also shown significant familial aggregation of CLL and related conditions including non-Hodgkin and Hodgkin lymphoma. Monoclonal B-cell lymphocytosis also aggregates in families with CLL. However, the clinical implication of familial aggregation is minimal given the overall rarity of CLL. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for loci that contribute to susceptibility, but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated immune function and other genes, but more studies are needed to verify these findings. The ability to conduct large-scale genomic studies will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate etiologic pathways.

scholarly journals Ethnic and age differences in right-left breast asymmetry in a large population-based screening population

2020 ◽  
Vol 93 (1105) ◽  
pp. 20190328 ◽  
Author(s):  
Sue M Hudson ◽  
Louise S Wilkinson ◽  
Rachel Denholm ◽  
Bianca L De Stavola ◽  
Isabel dos-Santos-Silva
Keyword(s):  
Breast Cancer ◽  
Ethnic Differences ◽  
Large Scale ◽  
Linear Trend ◽  
Large Population ◽  
Population Based ◽  
Left Breast ◽  
Breast Asymmetry ◽  
Time Asymmetry ◽  
Automated Measurements

Objective: Exposure to sex hormones is important in the pathogenesis of breast cancer and inability to tolerate such exposure may be reflected in increased asymmetrical growth of the breasts. This study aims to characterize, for the first time, asymmetry in breast volume (BV) and radiodense volume (DV) in a large ethnically diverse population. Methods: Automated measurements from digital raw mammographic images of 54,591 cancer-free participants (aged 47–73) in a UK breast screening programme were used to calculate absolute (cm3) and relative asymmetry in BV and DV. Logistic regression models were fitted to assess asymmetry associations with age and ethnicity. Results: BV and DV absolute asymmetry were positively correlated with the corresponding volumetric dimension (BV or DV). BV absolute asymmetry increased, whilst DV absolute asymmetry decreased, with increasing age (P-for-linear-trend <0.001 for both). Relative to Whites, Blacks had statistically significantly higher, and Chinese lower, BV and DV absolute asymmetries. However, after adjustment for the corresponding underlying volumetric dimension the age and ethnic differences were greatly attenuated. Median relative (fluctuating) BV and DV asymmetry were 2.34 and 3.28% respectively. Conclusion: After adjusting for the relevant volumetric dimension (BV or DV), age and ethnic differences in absolute breast asymmetry were largely resolved. Advances in knowledge: Previous small studies have reported breast asymmetry—breast cancer associations. Automated measurements of asymmetry allow the conduct of large-scale studies to further investigate these associations.

Richter syndrome epidemiology in a large population based chronic lymphocytic leukemia cohort from Norway

2019 ◽  
Vol 60 ◽  
pp. 128-133 ◽  
Author(s):  
Andrea Lenartova ◽  
Ulla Randen ◽  
Tom Børge Johannesen ◽  
Geir Erland Tjønnfjord
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Large Population ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Richter Syndrome

scholarly journals Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability

2015 ◽  
Vol 36 (1) ◽  
pp. 55-71 ◽  
Author(s):  
A Vilar-Bergua ◽  
I Riba-Llena ◽  
C Nafría ◽  
A Bustamante ◽  
V Llombart ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Vascular Disease ◽  
Large Scale ◽  
Small Vessel Disease ◽  
Large Population ◽  
Vascular Cognitive Impairment ◽  
Population Based ◽  
Endothelial Damage ◽  
Csf Biomarkers ◽  
Lacunar Infarcts

Vascular dementia is the second most common type of dementia after Alzheimer’s disease (AD). Subcortical ischemic vascular disease refers to a form of vascular cognitive impairment characterized by the presence of diffuse white matter hyperintensities (WMHs) and multiple lacunar infarcts. These neuroimaging findings are mainly caused by cerebral small-vessel disease (cSVD) and relate to aging and cognitive impairment, but they can also be silent and highly prevalent in otherwise healthy individuals. We aimed to review studies on blood and cerebrospinal fluid (CSF) markers related to the presence of WMHs and lacunar infarcts that have been conducted in the past in large population-based studies and in high-risk selected patients (such as those with vascular risk factors, vascular cognitive impairment, or AD). Relevant associations with the presence and progression of cSVD have been described in the blood for markers related to inflammatory processes, endothelial damage and coagulation/fibrinolysis processes, etc. Also, different combinations of CSF markers might help to differentiate between etiologic types of dementia. In the future, to translate these findings into clinical practice and use biomarkers to early diagnosis and monitoring vascular cognitive impairment would require the replication of candidate markers in large-scale, multicenter, and prospectively designed studies.

scholarly journals A review of HLA and COVID-19 association studies

2020 ◽  
Vol 3 (2) ◽  
pp. 25-30
Author(s):  
Renata Zunec
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Human Leukocyte ◽  
Genetic System ◽  
Epidemiological Studies ◽  
Population Based ◽  
Case Control ◽  
Case Control Studies ◽  
First Case ◽  
Scale Population

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is reported to vary across different populations in the prevalence of infection, in the death rate of patients, in the severity of symptoms and in the drug response of patients. Among host genetic factors that can influence all these attributes human leukocyte antigen (HLA) genetic system stands out as one of the leading candidates. Case-control studies, large-scale population-based studies, as well as experimental bioinformatics studies are of utmost importance to confirm HLA susceptibility spectrum of COVID-19. This review presents the results of the first case-control and epidemiological studies performed in several populations, early after the pandemic breakout. The results are pointing to several susceptible and protective HLA alleles and haplotypes associations with COVID-19, some of which might be of interest for the future studies in Croatia, due to its common presence in the population. However, further multiple investigations from around the world, as numerous as possible, are needed to confirm or deteriorate these preliminary results.

scholarly journals p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression

Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3452-3459 ◽  
Author(s):  
S el Rouby ◽  
A Thomas ◽  
D Costin ◽  
CR Rosenberg ◽  
M Potmesil ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Gene Mutations ◽  
P53 Gene ◽  
Lymphocytic Leukemia ◽  
P53 Mutations ◽  
P53 Gene Mutation ◽  
P53 Gene Mutations ◽  
Cell Chronic Lymphocytic Leukemia

We studied 53 patients with B-cell chronic lymphocytic leukemia (B-CLL) and found mutations of the p53 gene in 15%. Patients with p53 gene mutations were found to have an aggressive form of B-CLL disease characterized by advanced Rai stage, rapid lymphocyte doubling time (LDT), and resistance to chemotherapy. While 27 of 29 treated patients (93%) without p53 mutations achieved a partial remission, only one of seven treated patients (14%) with p53 mutations achieved a partial remission (P = .00009). Adjusting for prognostic factors (age, sex, race, and Rai stage), patients with p53 gene mutations had a 13-fold greater risk of death than patients without p53 mutations (P = .013). In addition to examining the clinical relevance of p53 gene mutations in B-CLL, we investigated the possible role of p53 gene regulation in the expression of the multidrug resistance genes MDR1 and MDR3. We quantitated MDR1 and MDR3 mRNA expression by reverse transcription- polymerase chain reaction (RT-PCR). Expression of both the MDR1 and MDR3 genes was independent of p53 gene mutation or prior drug treatment, and did not predict for clinical response. Our findings indicate that p53 gene mutations in B-CLL are associated with a poor clinical outcome and may be a prognostic indicator for drug resistance.

Mortality among Patients with Giant Cell Arteritis: A Large-scale Population-based Cohort Study

2019 ◽  
Vol 47 (9) ◽  
pp. 1385-1391 ◽  
Author(s):  
Niv Ben-Shabat ◽  
Shmuel Tiosano ◽  
Ora Shovman ◽  
Doron Comaneshter ◽  
Yehuda Shoenfeld ◽  
...  
Keyword(s):  
Cohort Study ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Median Survival ◽  
Mortality Risk ◽  
Large Scale ◽  
Large Population ◽  
Population Based ◽  
Medical Database ◽  
Age And Sex

Objective.Studies regarding mortality among patients with giant cell arteritis (GCA) have yielded conflicting results. Thus in this large population-based study we aimed to examine whether GCA is associated with increased mortality, and if so, the effect of age at diagnosis and sex on the association.Methods.We used the medical database of Clalit Health Services for this retrospective cohort study. Followup was from January 1, 2002, and continued until death or end of followup on September 1, 2018. Incident GCA patients were compared with age- and sex-matched controls. Estimated median survival times were calculated using the Kaplan-Meier method. HR for all-cause mortality were obtained by the Cox proportional hazard model, adjusted for sociodemographic variables and cardiovascular risk factors.Results.The study included 7294 patients with GCA and 33,688 controls. The mean age at start of followup was 72.1 ± 9.9 years with 69.2% females. Estimated median survival time was 13.1 years (95% CI 12.6–13.5) in patients with GCA compared with 14.4 years (95% CI 14.1–14.6) in controls (p < 0.001). The multivariate analysis demonstrated increased mortality risk in the first 2 years after diagnosis (HR 1.14, 95% CI 1.04–1.25) and > 10 years after diagnosis (HR 1.14, 95% CI 1.02–1.3). The mortality risk was higher in patients diagnosed at ≤ 70 years of age [HR 1.5 (95% CI 1.14–1.99) 0–2 yrs; HR 1.38 (95% CI 1.1–1.7) > 10 yrs].Conclusion.Patients with GCA have a minor decrease in longterm survival compared to age- and sex-matched controls. The seen difference is due to excess mortality in the first 2 years, and > 10 years after diagnosis. Patients diagnosed ≤ 70 years of age are at greater risk.

The bidirectional increased risk of B-cell lymphoma and T-cell lymphoma

Blood ◽  
2021 ◽  
Author(s):  
Dai Chihara ◽  
Graça Dores ◽  
Christopher Flowers ◽  
Lindsay M Morton
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
T Cell Lymphoma ◽  
Primary Lymphoma ◽  
Second Primary ◽  
Increased Risk

Lymphoma survivors have a significantly higher risk of developing second primary lymphoma than the general population; however, bidirectional risks of developing B- and T-cell lymphomas (BCL; TCL) specifically are less well understood. We used population-based cancer registry data to estimate the subtype-specific risks of second primary lymphoma among patients with first BCL (n=288,478) or TCL (n=23,747). We observed nearly five-fold increased bidirectional risk between BCL and TCL overall (TCL following BCL: standardized incidence ratio [SIR]=4.7, 95% confidence interval [CI]=4.2-5.2; BCL following TCL: SIR=4.7, 95%CI=4.1-5.2), but the risk varied substantially by lymphoma subtype. The highest SIRs were observed between Hodgkin lymphoma (HL) and peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (PTCL-NOS following HL: SIR=27.5, 95%CI=18.4-39.4; HL following PTCL-NOS: SIR=31.6, 95%CI=17.3-53.0). Strikingly elevated risks also were notable for angioimmunoblastic T-cell lymphoma (AITL) and diffuse large B-cell lymphoma (DLBCL) (AITL following DLBCL: SIR=9.7, 95%CI=5.7-15.5; DLBCL following AITL: SIR=15.3, 95%CI=9.1-24.2). These increased risks were strongest within the first year following diagnosis but remained persistently elevated even at ≥5 years. In contrast, SIRs were &lt;5 for all associations of TCL with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL). These patterns support etiologic heterogeneity among lymphoma subtypes and provide further insights into lymphomagenesis.

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