myelin-basic-protein and Lymphoma--Non-Hodgkin

The pattern-recognition pathway plays an important role in infection recognition and immune responses, and previous studies have suggested an association between genetic variation in innate immunity genes and non-Hodgkin lymphoma (NHL). We evaluated NHL risk associated with genetic variation in pattern-recognition genes using data from a case-control study of NHL conducted in Connecticut women. Single nucleotide polymorphisms (SNPs) in 27 pattern-recognition genes were genotyped in 432 Caucasian incident NHL cases and 494 frequency-matched controls. Unconditional logistic regression was used to compute odds ratios (ORs) for NHL and common NHL subtypes in relation to individual SNPs and haplotypes. A gene-based analysis that adjusted for the number of tagSNPs genotyped in each gene showed a significant association with overall NHL for the MBP gene (P = 0.028), with the diffuse large B-cell lymphoma (DLBCL) subtype for the MASP2 gene (P = 0.011), and with the follicular lymphoma (FL) subtype for DEFB126 (P = 0.041). A SNP-based analysis showed that MBP rs8094402 was associated with decreased risks of overall NHL (allele risk OR = 0.72, P-trend = 0.0018), DLBCL (allele risk OR = 0.72, P-trend = 0.036), and FL (allele risk OR = 0.67, P-trend = 0.021), while MASP2 rs12711521 was associated with a decreased risk of DLBCL (allele risk OR = 0.57, P-trend = 0.0042). We also observed an increased risk of FL for DEFB126 rs6054706 (allele risk OR = 1.39, P-trend = 0.033). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NHL or specific NHL subtypes, but these preliminary findings require replication in larger studies.

Topics: Adult; Aged; Aged, 80 and over; beta-Defensins; Case-Control Studies; Connecticut; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Immunity, Innate; Logistic Models; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mannose-Binding Protein-Associated Serine Proteases; Middle Aged; Myelin Basic Protein; Polymorphism, Single Nucleotide; Receptors, Pattern Recognition; White People; Young Adult

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Topics: Adolescent; Adult; Aged; Brain Diseases; Breast Neoplasms; Cerebrospinal Fluid Proteins; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Meningeal Neoplasms; Middle Aged; Myelin Basic Protein

A 26-year-old man developed transient bilateral internuclear ophthalmoplegia with exotropia after cranial irradiation and intrathecal administration of methotrexate for lymphoma. Resolution of the ophthalmoplegia and the decrease in abnormally high levels of cerebrospinal fluid myelin basic protein after discontinuation of intrathecal medication suggested demyelination from chemotherapy and irradiation.

Topics: Adult; Antineoplastic Agents; Brain; Humans; Injections, Spinal; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Myelin Basic Protein; Ophthalmoplegia; Radiotherapy