Citations

Summary A recent meta‐analysis of three genome‐wide association studies of chronic lymphocytic leukaemia ( CLL ) identified two common variants at the 6p21.31 locus that are associated with CLL risk. To verify and further explore the association of these variants with other non‐ H odgkin lymphoma ( NHL ) subtypes, we genotyped 1196 CLL cases, 1699 NHL cases, and 2410 controls. We found significant associations between the 6p21.31 variants and CLL risk (rs210134: P = 0·01; rs210142: P = 6·8 × 10 −3 ). These variants also showed a trend towards association with some of the other NHL subtypes. Our results validate the prior work and support specific genetic pathways for risk among NHL subtypes.

Abstract B24 Purpose Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States for which no recommended screening guidelines are available. An estimated 34,290 deaths related to PC is expected to occur in 2008 and the 5-year relative survival rate for this cancer is 5% for all stages combined. A person's chance of developing this cancer increases three-fold if a first-degree relative has pancreatic cancer. The purpose of this study was to assess attitudes of unaffected family members in the Mayo Clinic Pancreas Cancer Family study toward PC cancer risk and future screening options. This is the first study to report such attitudes of PC family members. Subjects and Methods At-risk family members with two or more relatives affected with pancreas cancer in the kindred and primary care controls completed a survey asking about: perceived PC risk, degree of PC worry/concern, attitude toward cancer screening in general, and intentions regarding PC screening if it were a blood test or endoscopic ultrasound. Results 386 family members in 109 PC kindreds and 1058 controls completed surveys. Forty-six percent of PC family members reported that it was likely they would develop PC during their lifetime compared to 6% of controls. Forty-one percent of family members reported having thoughts regarding the possibility of getting pancreatic cancer during the past month versus 4.6% of controls. Similarly, 74% of family members reported concern about getting PC as compared to 40.6% of controls. 94% of family members reported they would be likely to undergo a blood-based PC screening test compared to 89.7% of controls. For endoscopic ultrasound, 71% of family members would be likely to undergo screening as compared to 55% of controls. All comparisons were statistically significant. Conclusion Compared to controls, PC family members perceive their personal PC risk to be high and report a higher rate of PC-related cancer worry/concern. A high percentage of family members and controls indicate receptivity to PC screening, especially if it were a blood test. If the screening is more invasive (i.e. EUS), interest declines, particularly among controls. This information can help investigators to understand and address potential motivators and barriers to recruitment for future PC studies and indicates that there is a need to develop educational interventions among these families to reduce their actual and perceived pancreatic cancer risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B24.

Assistive equipment has helped lower task demands and back stress for patient-handlers; however, limited research exists on the psychological benefits (i.e., safety and comfort) of self-transfer devices for patients in postoperative care. A study was conducted to determine the efficacy of a bed assistive device in a patient population; the objectives were to compare self-perceived recovery measures and usage of pain medication between patients in the Control ( n = 8; age, 34 ± 6.3years) and Device ( n = 7; 41 ± 12) groups. Fifteen female participants undergoing either abdominal hysterectomy ( n = 6) or Cesareansection ( n = 9) procedures were recruited for the study. Both groups completed a total of twelve questionnaires over a five-week recovery period. The Device Group reported higher levels of energy, less pain interference, lower perceived pain, less reliance on pain medication and returned to activities of daily living faster than the Control Group.

In the bone marrow cavity, adipocyte numbers increase, whereas osteoblast progenitor numbers decrease with aging. Because adipocytes and osteoblasts share a common progenitor, it is possible that this shift is due to an increase in adipocyte-lineage cells at the expense of osteoblast-lineage commitment. Estrogens inhibit adipocyte differentiation, and in both men and women, circulating estrogens correlate with bone loss with aging. In bone cells, estrogens stimulate expression of TGF-β and suppress mesenchymal cell adipogenesis. Using a tripotential mesenchymal cell line, we have examined whether estradiol suppression of adipocyte differentiation is due to stimulation of TGF-β and the mechanism by which TGF-β suppresses adipogenesis. We observed that estradiol-mediated suppression of adipogenic gene expression required at least 48 h treatment. TGF-β expression increased within 24 h of estradiol treatment, and TGF-β inhibition reversed estradiol influences on adipogenesis and adipocyte gene expression. Connective tissue growth factor (CTGF) mediates TGF-β suppression of adipogenesis in mouse 3T3-L1 cells. CTGF expression was induced within 24 h of TGF-β treatment, whereas estradiol-mediated induction required 48 h treatment. Moreover, estradiol-mediated induction of CTGF was abrogated by TGF-β inhibition. These data support that estradiol effects on adipogenesis involves TGF-β induction, which then induces CTGF to suppress adipogenesis.

AbstractFree light chains (FLCs) are the most commonly detected paraproteins in chronic lymphocytic leukemia (CLL). We examined the types of FLC abnormalities and prognostic utility of the FLC assay compared with standard prognostic biomarkers in a prospective cohort of 339 patients with newly diagnosed CLL. Three types of FLC abnormalities were identified: monoclonal elevated FLC (elevated κ and/or λ with abnormal FLC ratio), polyclonal elevated FLC (elevated κ and/or λ with normal FLC ratio), and ratio-only FLC abnormality (normal range κ and λ with abnormal FLC ratio). One hundred sixty-five patients (49%) had a FLC abnormality with approximately equal distribution among monoclonal elevation, polyclonal elevation, and ratio-only abnormality. All FLC abnormalities were associated with poor time to first treatment: monoclonal FLC (hazard ratio [HR], 4.99; 95% confidence interval [CI], 2.94-8.48), polyclonal FLC (HR, 2.40; 95% CI, 1.24-4.64), ratio-only FLC (HR, 2.57; 95% CI, 1.40-4.69). Monoclonal FLC and polyclonal FLC were associated with poor overall survival compared with patients with normal FLC. Results remained significant after adjusting for Rai stage. The FLC assay is a simple, widely available clinical test with similar prognostic utility as routinely used prognostic biomarkers for CLL. Among persons with FLC abnormalities, the type of abnormality affects prognostic significance.

Pregnancy-associated plasma protein-A2 (PAPP-A2) is a novel homolog of PAPP-A in the metzincin superfamily. However, compared with the accumulating data on PAPP-A, very little is known about PAPP-A2. In this study, we determined the tissue expression pattern of PAPP-A2 mRNA in wild-type (WT) mice and characterized the phenotype of mice with global PAPP-A2 deficiency. Tissues expressing PAPP-A2 in WT mice were more limited than those expressing PAPP-A. The highest PAPP-A2 mRNA expression was found in the placenta, with abundant expression in fetal, skeletal, and reproductive tissues. Heterozygous breeding produced the expected Mendelian distribution for the pappa2 gene and viable homozygous PAPP-A2 knockout (KO) mice that were normal size at birth. The most striking phenotype of the PAPP-A2 KO mouse was postnatal growth retardation. Male and female PAPP-A2 KO mice had 10 and 25–30% lower body weight, respectively, than WT littermates. Adult femur and body length were also reduced in PAPP-A2 KO mice, but without significant effects on bone mineral density. PAPP-A2 KO mice were fertile, but with compromised fecundity. PAPP-A expression was not altered to compensate for the loss of PAPP-A2 expression, and proteolysis of PAPP-A2's primary substrate, IGF-binding protein-5, was not altered in fibroblasts from PAPP-A2 KO embryos. In conclusion, tissue expression patterns and biological consequences of gene KO indicate distinct physiological roles for PAPP-A2 and PAPP-A in mice.