Interaction between dietary and lifestyle risk factors and N-Acetyltransferase polymorphisms in B-Cell lymphoma etiology

Background: Gene-environment interactions are suggested to play a role in lymphomagenesis. Methods: We tested the interaction between the NAT1/NAT2 phenotype, as inferred by the respective genotypes, and exposure to dietary and lifestyle risk factors, in 199 incident lymphoma cases and 188 population controls. We used unconditional logistic regression to calculate the odds ratio (OR) and its 95% confidence interval for lymphoma (all subtypes combined) and B cell lymphoma, associated to the rapid NAT1 phenotype and to the intermediate and slow NAT2 phenotype, and to the estimated dietary intake of heterocyclic amines and folate, current smoking, coffee, and use of permanent hair dyes, as well as the respective interaction terms. We adjusted the ORs by age, gender, and education, and we used the likelihood ratio test to test the interaction between the NAT1, NAT2 phenotype and the dietary and lifestyle variables. Results: We observed an increase in risk of lymphoma (all subtypes combined) and B-cell lymphoma in particular associated with the estimated above median dietary intake of heterocyclic amines (OR = 4.2, 95%CI 1.2 – 14.8) and folate (OR = 4.1, 95%CI 0.7 – 22.4) among subjects with the NAT1 rapid acetylator phenotype, but not independent on the NAT1 phenotype. The test for interaction was significant for heterocyclic amines, but not for folate (p for interaction = 0.026 and 0.076 respectively). Ever use of permanent hair dyes was associated with an elevated risk independent on the NAT1, NAT2 phenotypes; risk decreased to null among intermediate and slow NAT1 acetylators (p for interaction = 0.010). Conclusions: Our results suggest that NAT1, NAT2 polymorphisms interact with dietary and lifestyle exposures in modulating risk of lymphoma and particularly B-cell lymphoma

Experimental study of Compton scattering reduction in digital mammographic imaging

In mammography, the first cause of image contrast reduction arises from the photons scattered inside the examined organ. The amount of Compton scattering strongly depends on the irradiation area and on the distance between the organ and the X-ray detector. We have experimentally evaluated how these geometrical conditions affect the scattering fraction. Our experimental setup includes a single photon counting device based on a silicon pixel detector as X-ray sensor; a lucite cylinder to simulate the breast tissue, and a lead collimator to define the irradiation area. We have evaluated the contrast and the signal-to-noise ratio for images acquired in different conditions

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study

Objectives: This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods: We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case–control study, conducted in six European countries in 1998–2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results: We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01–4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00–4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95–4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions: Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma

Study of GaAs detectors characteristics for medical imaging

In this work we present the results of a systematic study about SI GaAs detectors as a function of substrate and contact type, geometry and thickness. This study has been stimulated from the interest in using GaAs as a detector for medical imaging applications. GaAs detectors have been produced using crystals grown with different techniques and changing both the thickness (in the range 200 μm-1 mm) and the contacts type and geometry. We have measured the current-voltage characteristics and, using radioactive sources (109Cd, 20 keV photons, 241Am, 60 keV photons, 99mTc, 140 keV photons), we have studied the performance of our detectors in terms of charge collection efficiency and energy resolution as a function of the bias voltage. Besides we have also studied the electrical and spectroscopic properties of GaAs detectors with different types and concentrations of the dopants in the substrate. So we have found the optimal doping type and concentration to have the best spectroscopic performances and the higher breakdown voltage. Simulation programs made with Monte Carlo methods have been developed to describe the electric field distribution and the transport of charge carriers toward the electrodes in GaAs detectors. In these simulations we have considered the presence of deep energy levels in the bandgap, the thickness, the bias voltage and the charge deposition in the crystal after photon interaction

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

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

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

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

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

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 three new genome-wide association studies (GWAS) and one prior scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of nine 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; $P=2.33x10^{-21}$), rs2523607 at 6p21.33 (HLA-B; $2.40x10^{-10}$), rs79480871 at 2p23.3 (NCOA1; $P=4.23x10^{-8}$), and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; $P=9.98x10^{-13}$ and $P=3.63x10^{-11}$, respectively). These data provide substantial new evidence for genetic susceptibility to this B-cell malignancy, and point towards pathways involved in immune recognition and immune function in the pathogenesis of DLBCL

“Acute leukemias and molecular markers, cooperative study between Cancer Hospital A.Businco Cagliari and Cancer Institute S.O.L.C.A of Cuenca in (EC).”

This molecular study on acute leukaemias is the result of the collaboration between Department of Haematology and Transplant of Cancer Hospital Businco, of Cagliari(I) and Molecular laboratory of Cancer Institute S.O.L.C.A. of Cuenca (EC). Prognosis, diagnosis and follow up in children an adults with Acute leukemias have been studied. Source of Ecuadorian samples were patients who come from Azuay countries, Loya, El Oro, Rio Paute. Countries with high deforestation tax, few health services, high use in agriculture of chemicals associated with high poverty level and high incidence of chronic disease in blood, pneumonia, breast. Ecuadorian population studied is included in a geographic area of 700.000 km2, 6% were Indios, 0.25% nigger, 94% half-caste white. Ecuadorian incidence of Acute limphoblastic Leukemias was 3.0 /year/100.000 people; AML 1.4 /year/100.000 people. High frequency were observed in children (0-14 years) with a 66% of tumor deaths. Among ALL pediatric case, 80% were type B, among B-ALL 72% case of adults were type L2 and 75% of children type L1 according to F.A.B. classification. Molecular analysis were performed in Cuenca( EC) and only samples of positive case were sent in molecular Biology of Cagliari for confirmation of results and sequence analysis. Objective. To create a new molecular laboratory for ALL/AML diagnosis in Cuenca (EC) was the aim of the study. Materials. From February 2000 to February 2005 in Cancer Institute S.O.L.C.A of Cuenca (EC ) 261 cases (137 male, 124 female) with lymphoprolipherative disease,119 of them were acute leukemias (38 AML and 81 ALL)) were analyzed. Methods. All cases were evaluated with Polymerase chain reaction, BIOMED I PCR protocol were performed to value t(1;19), t(9;22), t(8;21), t(15;17), t(12;21) rearrangements, while for MLL rare translocations study t(6;11),t(9 ;11) t(11;19) were been used probes and procedure kindly provided from Instituts fur Pharmazeutische Biologie JWG Universitaet Frankfurt. Results. The 15% of patients showed genetic alterations (12% in adults and 14% in children), 1% of children were positive to 1 Chromosome deletion. In ALL, 1 case (1.23%) was positive to t(4:11) rearrangement, all results were tested with BIOMED I protocol and confirmed with sequence analysis. Considerations and conclusions. Molecular Results of patients in Cuenca (EC) were confirmed with results of same samples sent to Cagliari. To our collaboration, after 6 years the molecular laboratory of Cancer Institute S.O.L.C.A. of Cuenca (EC) is an independent structure for molecular diagnosis in leukemia, lymphomas, transplant and cordonal blood procedure