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The human concentrative nucleoside transporter (hCNT2), also known as SLC28A2, plays an important role in the cellular uptake across intestinal membrane of some naturally occurring nucleosides and nucleoside analogs. This study aims to determine the genetic variability of hCNT2 (SLC28A2) in three major Asian ethnic groups residing in Singapore: Chinese, Malay and Indian, and functionally characterize the variants of hCNT2. Healthy participants (n=96) from each group were screened for genetic variations in the exons of hCNT2 (SLC28A2) using denaturing high performance liquid chromatography and sequencing analyses. A total of 23 polymorphisms were identified in the exonic and flanking intronic regions, and ethnic differences in single nucleotide polymorphism frequencies were evident. Five novel nonsynonymous variants (L12R, R142H, E172D, E385K, M612T) were constructed by mutagenesis and functionally characterized in U-251 cells. Expression of these variants in U-251 cells revealed that all except E385K can uptake various substrates of hCNT2: inosine, ribavirin and uridine.

Background: Non-Hodgkin's lymphoma has increased in incidence in many countries, particularly in the West. Advances in diagnostic methods and the understanding of the disease over time pose a challenge to the interpretation of these trends. The aim of this study was to determine if the disease has increased in Singapore, a newly industrialized Asian country, and to examine the possible factors that may account for any observed changes., Methods: Data from the population-based Singapore Cancer Registry for the period 1968 to 1992 were reviewed to determine time trends based on sex and ethnic group. The Poisson regression model was fitted to the cross-tabulated data to obtain the adjusted incidence density ratios., Results: A total of 1988 cases of non-Hodgkin's lymphoma were included in the analysis. There was an overall increase in incidence among both Chinese and Malaysians. However, the rate of increase was greater in females (age-standardized rate from 1.8 per 100,000 in 1968-1972 to 4.5 per 100,000 in 1988-1992) than in males (3.2 per 100,000 to 5.9 per 100,000 in the same time periods). Between ethnic groups, Malay females were at higher overall risk compared with their Chinese counterparts (incidence density ratio 1.32; 95% confidence interval, 1.08-1.61). Although a substantial proportion of patients diagnosed with Hodgkin's disease between 1968 and 1972 were reclassified on review, using present criteria, as having non-Hodgkin's lymphoma, it is unlikely that this, and other recent changes in histologic interpretation, could have accounted for an increase of this magnitude., Conclusions: Non-Hodgkin's lymphoma has increased in incidence among the Chinese and Malay populations in Singapore. The pattern of increase differs from that of the common cancer sites, and suggests the need to look for environmental and genetic factors that have not yet been elucidated.