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PURPOSE: This study sought to describe the physical activity-endometrial cancer association and potential mediation of this relationship by obesity in midlife. METHODS: Participants were 67,705 women (aged 50-71 years) enrolled in the NIH-AARP cohort who reported their historical leisure-time physical activity patterns starting at age 15-18 years. We identified five long-term physical activity patterns between adolescence and cohort entry (i.e., inactive, maintained-low, maintained-high, increasers, decreasers). We used Cox regression (Hazard ratio - HR [95% CI]) to assess the relationship between these patterns and midlife obesity and endometrial cancer, adjusting for covariates. Mediation analysis was used to decompose the physical activity patterns-endometrial cancer association to estimate the proportion of the physical activity-endometrial cancer association mediated by midlife obesity. RESULTS: During an average 12.3 years of follow-up 1,468 endometrial cancers occurred. Long-term physical activity patterns were inactive, maintained-low, maintained-high, increasers, and decreasers. Compared to long-term inactive women, women who maintained-high or increased activity levels had a 19-26% lower risk for endometrial cancer (maintained-high: HR = 0.81 [0.67, 0.98]; increasers: HR = 0.74 [0.61, 0.91]). They also had a 45-77% lower risk for obesity in midlife (e.g., maintained-high, BMI 30-39.9: HR = 0.50 [0.46, 0.55]; maintained-high, BMI 40+: HR = 0.32 [0.26, 0.39]). Obesity was a significant mediator and appeared to account for 55-63% of the physical activity-endometrial cancer associations observed. CONCLUSIONS: Both initiating and maintaining physical activity throughout adulthood can play a role in preventing obesity and in turn, lowering the risk for endometrial cancer. [ABSTRACT FROM AUTHOR]

The molecular hallmark of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) is the expression of 1 of 2 alternate forms of the aberrant BCR-ABL protein-p210BCR-ABL or p190BCR-ABL. The presence of BCR-ABL message provides a target for analyzing the lineage derivation of this disease. We, therefore, studied myeloid and erythroid progenitor involvement in Philadelphia chromosome-positive ALL. Bone marrow low-density cells from Philadelphia chromosome-positive ALL patients (5 with the p190BCR-ABL and 2 with the p210BCR-ABL anomaly) were cultured in the mixed colony culture assay. cDNA from individually plucked colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies was then analyzed using the hybridization protection assay in conjunction with the polymerase chain reaction to detect BCR-ABL molecular aberrations. Colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies from 1 of 5 p190BCR-ABL-positive patients and 1 of 2 p210BCR-ABL-positive patients expressed BCR-ABL transcripts, whereas colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies from the other patients did not. Our study suggests that the origin of both p190BCR-ABL- and p210BCR-ABL-positive ALL is heterogenous with involvement of either a pluripotent precursor or a lymphoid lineage-committed hematopoietic progenitor.

Oncogenes of retroviruses are directly related to cancers in animals; however, finding relevant associations with human cancer has been difficult. Studies reported here were designed to assess the extent of protooncogene transcription in human leukemias as compared to normal cells. Low-stringency hybridization of viral oncogene DNAs to cell messenger RNAs was done to determine whether evolutionarily divergent oncogene sequences were increased in leukemic cells. Several oncogenes hybridized at low levels to normal messenger RNAs. Some oncogene transcripts in fresh leukemic cells of 28 patients were present at higher levels than in normal cells. The oncogenes abl, erb, myc, and ras were expressed in all normals tested and a majority of the leukemic cells. However, fes, fps, and src probes hybridized rarely to transcripts in normal cells although more frequently to messenger RNA from leukemic cells. No oncogenes were expressed in specific patterns by cell types. It is concluded that transformation of human hematopoietic cells involves more than one oncogene and may include sequences unrelated to retroviruses.

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.