ABSTRACT
Genetic variation in immune-related genes, such as IL10 and TNF, have been associated with the development of non-Hodgkin lymphoma (NHL) in Caucasian populations. To test the hypothesis that IL10 and TNF polymorphisms may be associated with NHL risk in Asian populations, we genotyped 20 single nucleotide polymorphisms (SNPs) within the IL10 and TNF/LTA loci in three independent case-control studies (2635 cases and 4234 controls). IL10 rs1800871, rs1800872, and rs1800896 were genotyped in all three studies, while 5 of the remaining SNPs were genotyped in two studies, and 12 in a single study. IL10 rs1800896 was associated with B cell lymphoma [per-allele odds ratio (OR) = 1.25, 95 % confidence interval (CI) 1.08-1.45; p trend = 0.003], specifically diffuse large B cell lymphoma (DLBCL) (per-allele OR = 1.29, 95 % CI 1.08-1.53; p trend = 0.004), as well as T cell lymphoma (per-allele OR = 1.44, 95 % CI 1.13-1.82; p trend = 0.003). TNF rs1800629, which was genotyped in only two of our studies, was also associated with B cell lymphoma (per-allele OR = 0.77, 95 % CI 0.64-0.91; p trend = 0.003), specifically DLBCL (per-allele OR = 0.69, 95 % CI 0.55-0.86; p trend = 0.001). Our findings suggest that genetic variation in IL10 and TNF may also play a role in lymphomagenesis in Asian populations.
Subject(s)
Asian People/genetics , Interleukin-10/genetics , Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/genetics , Polymorphism, Single Nucleotide , Tumor Necrosis Factors/genetics , Adult , Aged , Case-Control Studies , China/epidemiology , Female , Hong Kong/epidemiology , Humans , Male , Middle Aged , Republic of Korea/epidemiology , RiskABSTRACT
Race, age, sex, and environmental conditions have significant impacts on lymphocyte subset values. It is important to establish the local reference ranges from healthy and non-HIV-positive adults in the local population for clinical decision making. In this study, the reference ranges for lymphocyte subsets among Chinese adults were established by analysis by single-platform flow cytometry of the lymphocyte compositions of 273 healthy adult blood donors between 17 and 59 years of age. The 95% reference ranges for CD3(+) T cells, CD3(+) CD4(+) T helper cells, and CD3(+) CD8(+) T suppressor cells are 723 to 2,271 cells/µl, 396 to 1,309 cells/µl, and 224 to 1,014 cells/µl, respectively. The 95% reference ranges for CD19(+) B cells and CD56(+) NK cells are 118 to 645 cells/µl and 61 to 607 cells/µl, respectively. Significant gender and age differences in the lymphocyte subsets have been demonstrated. Our results have also shown that the T-lymphocyte compositions in Hong Kong Chinese were comparable to those of other Asian populations but were different from those of Caucasians.
Subject(s)
Flow Cytometry/methods , Lymphocyte Subsets/immunology , Adolescent , Adult , Age Factors , Asian People , Blood Donors , Female , Hong Kong , Humans , Male , Middle Aged , Reference Values , Sex Factors , Young AdultABSTRACT
The genetic basis of chronic lymphocytic leukemia (CLL) has not been fully elucidated to date. Although it is the most common haematological malignancy in Caucasians, it is uncommon among Asians. A recent genome-wide scan of CLL in Caucasians, which was carried out in the UK, identified six variants showing strong association. We attempted to replicate these findings in 71 patients with CLL and 1273 controls in Hong Kong Chinese. Three of the six variants were significantly associated with CLL. The rs872071 variant (Odds Ratio (95% Confidence Interval) = 1.78 (1.25-2.53), P = 0.0013) in the IRF4 gene region showed the strongest association, similar to that reported in the UK study. Polymorphisms in SP140 and ACOXL were also associated with risk of CLL. Further, the mean allele frequencies of the six variants were moderately (59%) to extremely (0.5%) lower in the Chinese population compared with Caucasians. These results suggest that variants in three loci may contribute to risk of CLL among Chinese.
Subject(s)
Genetic Predisposition to Disease , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Alleles , Antigens, Nuclear/genetics , Asian People , Female , Gene Frequency/genetics , Hong Kong/epidemiology , Humans , Interferon Regulatory Factors/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Male , Polymorphism, Single Nucleotide , Risk Factors , Transcription Factors/genetics , United Kingdom , White PeopleABSTRACT
Cytogenetically-unrelated clones are infrequently seen in hematologic malignancies, and are particularly uncommon in acute lymphoblastic leukemia. We report a case of T-cell acute lymphoblastic leukemia with L2 morphology which demonstrated three cytogenetically distinct clones: 46,XY,t(2;9)(p21;q34)/46,XY,del(6)(q21q23)/47,XX,+8. Interphase cytogenetic analysis by fluorescence in situ hybridization (FISH) confirmed the presence of trisomy 8 in a significant proportion of lymphoblasts, while reverse transcription-polymerase chain reaction (RT-PCR) did not show the presence of BCR/ABL fusion. This is the first report describing the occurrence of cytogenetic triclonality in de novo T-cell acute lymphoblastic leukemia.
