Low frequency of BCL-2/JH translocation in peripheral blood lymphocytes of healthy Japanese individuals

Abstract

The incidence of follicular lymphoma differs significantly between white and Japanese individuals. Translocation between the BCL-2 and immunoglobulin heavy chain genes is detected in 85% to 90% of all follicular lymphomas in whites. Recently, BCL-2/J H translocation was detected in peripheral blood lymphocytes from more than 50% of healthy white individuals. To clarify the reason for the difference in incidence of follicular lymphoma between whites and Japanese, the frequency of BCL-2/J H translocation in peripheral blood lymphocytes of healthy Japanese individuals was compared with that of German individuals. The prevalence of BCL-2/J H translocation in Japanese adults appeared to be significantly lower than that in German adults. The present data suggest that the low frequency of BCL-2/J H translocation in the Japanese general population may be one of the major reasons for the difference in incidence of follicular lymphoma between whites and Japanese. IntroductionThe incidence of follicular lymphoma differs between white and Japanese individuals, accounting for about 40% of all non-Hodgkin lymphomas in whites, compared with less than 10% in Japanese. [1][2][3][4][5] The age-adjusted incidence of follicular lymphoma (per 100 000) is reported to be 3.8 in the United States and 0.5 in Japan. 2 The reason for this difference between the 2 populations is unknown.The translocation t(14;18)(q32;q21) between the BCL-2 protooncogene and the J H immunoglobulin gene region is detected in 85% to 90% and approximately 50% of all follicular lymphomas in whites and Japanese, respectively. [5][6][7][8][9][10] This leads to overexpression of BCL-2, conferring a growth advantage on the neoplastic cells. 11 Recently, it has been reported that BCL-2/J H translocation is frequently detected in peripheral blood lymphocytes of healthy white individuals. [12][13][14][15][16][17] In the multihit theory of tumorigenesis, translocation of the BCL-2 gene is considered to be the first somatic mutation, and additional mutations are needed for development of follicular lymphoma. From this viewpoint, the low incidence of follicular lymphoma in Japanese individuals may be due to the low frequency of BCL-2/J H translocation in the general population or other factors affecting lymphomagenesis. Accordingly, we compared the frequency of BCL-2/J H translocation in peripheral blood lymphocytes of Japanese individuals with that of German individuals. The results showed that the incidence of BCL-2/J H translocation in healthy Japanese individuals is significantly lower than that in German individuals. Study designPeripheral blood mononuclear cells were obtained with informed consent from Japanese and German (white) individuals who had no serious diseases, and the DNA was extracted using standard procedures. The DNA samples from German individuals were sent to Japan and used for experiments. The presence of the BCL-2/J H translocation in the major breakpoint region (MBR) of the BCL-2 gene was examined using a nested polymerase chain reaction (PCR), a...

Chromosome Translocations in Workers Exposed to Benzene

“…The frequency of the t(14;18) -positive lymphocytes with more than 10 copies detected in healthy Chinese individuals (55%) was similar to previous frequencies reported for Caucasian populations ( 15 , 34 ) and higher than that reported for Japanese individuals (16%) ( 34 ). The Chinese have a similarly lower level of lymphoma as the Japanese in comparison to Western Caucasian populations.…”

BCL‐2/JH translocation in peripheral blood lymphocytes of unexposed individuals: Lack of seasonal variations in frequency and molecular features

“…7,9,10,12 All sequenced PCR products contained a fragment of the 5Ј BCL-2 (MBR) locus and 1 of the 6 3Ј-J H regions, separated by an inserted sequence of varying length probably resulting from illegitimate V(D)J recombination (Table I). 17 Although there are some discrepancies, the BCL-2 breakpoints tended to fall into 3 clusters regions: bp 3055, 3115 and 3165 (less frequently) (Fig.…”

“…Occurring in 85% of human follicular lymphoma and in 20% of diffuse large cell lymphoma, 6 it is also present in peripheral blood lymphocytes of healthy individuals. [7][8][9][10][11][12] Before studying the effect of pesticide exposure among farmers, it is necessary to evaluate the influence of potential confounding factors. Pesticide use follows a temporal cycle with potential effects on biomarkers of season-related environmental factors.…”

The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells

“…The reported mean prevalence of t(14;18) in peripheral blood of healthy individuals is 36%, ranging from 8 to 100%, depending on the sensitivity of the PCR assays used to detect t(14;18). [4][5][6][7][8][9] In our study, quantitative levels of t(14;18) in healthy donors were low (o0.01%). This finding also correlates well with other studies that have shown a low quantity of cells carrying t(14;18) in individuals without FL.…”

“…3 Although this translocation is classically associated with FL, many studies have reported the presence of t(14;18) in healthy individuals who do not have FL. [4][5][6][7][8][9][10][11] Allogeneic stem cell transplantation (allo-SCT) is of increasing interest as a therapeutic option for patients due to the potential of a graft-versus-lymphoma effect to provide long-term disease control. [12][13][14][15] We have recently reported that monitoring the tumor load of t(14;18) cells by real-time quantitative PCR (RQ-PCR) may predict the outcome of FL patients after allo-SCT.…”