Risk of follicular lymphoma associated with BCL2 translocations in peripheral blood

Abstract

Many adults have circulating lymphocytes with the BCL2 gene translocation characteristic of follicular lymphoma. We therefore conducted a nested case–control study of incident lymphomas with peripheral blood obtained a median 4.9 years pre-diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Overall, 13 of 26 cases of lymphoma and 14 of 47 controls had BCL2 major breakpoint region (MBR) translocations in pre-diagnosis blood (odds ratio [OR] = 2.8). Nine cases had BCL2-MBR-positive tumors; eight of these nine had BCL2-MBR translocations in paired blood versus five of the 17 with BCL2-MBR-negative tumors (p = 0.01). Comparing both tumor types to controls, blood BCL2-MBR translocations had a strong, statistically significant association with BCL2-MBR-positive tumors (OR = 26), but not with BCL2-MBR-negative tumors (OR = 0.9). All eight BCL2-MBR-positive tumors with pre-diagnosis BCL2 translocations were clonally related to these circulating cells, based on similarity of recombination sequences. These data indicate that blood BCL2-MBR translocations represent lymphoma precursor clones with malignant potential.

Keywords::

• Lymphoma and Hodgkin disease
• molecular genetics
• prognostication

Acknowledgements

The authors would like to thank Mss. Manuela Neubert and Ute Pett of the University of Greifswald, Drs. Christine Berg and Philip Prorok of the NCI Division of Cancer Prevention, Ms. Barbara O’Brien and the staff of Westat, Inc., Mr. Thomas Riley and the staff of Information Management Services, Inc., the screening center investigators and staff of the PLCO Cancer Screening Trial and the trial participants for their contributions to this study. This work was supported by the Intramural Research Program and extramural contract funds of the National Cancer Institute at the National Institutes of Health.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

Supplementary material available online

Supplementary Tables I & II showing further data.