Dioxin emissions from a municipal solid waste incinerator and risk of invasive breast cancer: a population-based case-control study with GIS-derived exposure.

BACKGROUND: To date, few epidemiologic studies have examined the relationship between environmental PCDD/F exposure and breast cancer in human populations. Dioxin emissions from municipal solid waste incinerators (MSWIs) are one of the major sources of environmental dioxins and are therefore an exposure source of public concern. The purpose of this study was to examine the association between dioxins emitted from a polluting MSWI and invasive breast cancer risk among women residing in the area under direct influence of the facility. METHODS: We compared 434 incident cases of invasive breast cancer diagnosed between 1996 and 2002, and 2170 controls randomly selected from the 1999 population census. A validated dispersion model was used as a proxy for dioxin exposure, yielding four exposure categories. The latter were linked to individual places of residence, using Geographic Information System technology. RESULTS: The age distribution at diagnosis for all cases combined showed a bimodal pattern with incidence peaks near 50 and 70 years old. This prompted us to run models separately for women aged 20-59 years, and women aged 60 years or older. Among women younger than 60 years old, no increased or decreased risk was found for any dioxin exposure category. Conversely, women over 60 years old living in the highest exposed zone were 0.31 time less likely (95% confidence interval, 0.08-0.89) to develop invasive breast cancer. CONCLUSION: Before speculating that this decreased risk reflects a dioxin anti-estrogenic activity with greater effect on late-onset acquired breast cancer, some residual confounding must be envisaged.

c-Flip protein expression in Burkitt's lymphomas is associated with a poor clinical outcome.

The World Health Organization Classification of Lymphoid Neoplasms identifies Burkitt's lymphoma/leukaemia (BL) as a single entity, characterized by unique clinical and genetic features that require specific high intensity chemotherapy regimens. Although remarkable successes in the treatment of the disease have been observed, when compared with paediatric patients, adults are less likely to reach stable complete remission. We investigated 32 BL cases, composed in equal part by adults and children that were treated with the French LMB regimen, for factors that may be implicated in chemoresistance. Immunohistochemical detection of procaspase-8, caspase-3a, survivin, p53, CD95, c-Flip and Phospho-RelA (Ser536) was investigated on paraffin-embedded tissues. The expression of c-Flip was found highly related to a poor prognosis, mostly characterized by adults with a chemoresistant disease, resulting in a high death rate within the first year of diagnosis. The 2-year overall survival with c-Flip expression was 24% compared with 93% in the absence of this marker (P = 0.04). All c-Flip-positive BL cases presented a nuclear Phospho-RelA (Ser536) localization, suggesting the presence of an active nuclear factor (NF)-kappa B transcription pathway. These findings show that c-Flip could be a reliable prognostic factor in BL, suggesting new therapeutic approaches that target the NF-kappa B pathway.

Long-term toxicity of antithymocyte globulin induction may vary with choice of agent: a single-center retrospective study.

BACKGROUND: Antithymocyte globulin (ATG) preparations are frequently used as induction treatment in renal transplantation, but little is known about the clinical equivalence of these different agents. We performed a retrospective, single-center study to compare the long-term clinical effects of ATG Fresenius (ATGF) and Thymoglobulin (SangStat, Fremont, CA) in renal transplant recipients. PATIENTS AND METHODS: A total of 194 consecutive renal transplant recipients were included who had undergone transplantation in our center between June 1993 and April 2001 and had received ATGF or Thymoglobulin as induction treatment. RESULTS: A total of 129 patients received ATGF and 65 patients received Thymoglobulin. Thirty patients (23%) in the ATGF group demonstrated cytomegalovirus (CMV) disease, whereas 24 patients (37%) in the Thymoglobulin group demonstrated CMV (P =0.02). Five patients (3.9%) in the ATGF group and eight patients (12.3%) in the Thymoglobulin group developed posttransplant malignancy (P =0.01). Five patients (3.9%) in the ATGF group and nine patients (13.8%) in the Thymoglobulin group died during follow-up (P =0.005). Cox regression analysis revealed that Thymoglobulin was an independent predictor of CMV disease (relative risk [RR] 2.16, confidence interval [CI] 95% [1.04-4.48]), malignancy (RR 2.16, CI 95% [1.04-4.48]), and death (RR 4.14, CI 95% [1.36-12.6]). CONCLUSION: In renal transplant recipients, induction therapy with Thymoglobulin seems to be associated with a significantly greater incidence of CMV disease, malignancy, and death compared with ATGF.

Dioxin emissions from a solid waste incinerator and risk of non-Hodgkin lymphoma.

BACKGROUND: It is not clear whether low environmental doses of dioxin affect the general population. We previously detected a cluster of patients with non-Hodgkin lymphoma around a French municipal solid waste incinerator with high dioxin emissions. To explore the environmental route suggested by these findings, we carried out a population-based case-control study in the same area. METHODS: We compared 222 incident cases of non-Hodgkin lymphoma diagnosed between 1980 and 1995 and controls randomly selected from the 1990 population census, using a 10-to-1 match. Dioxin ground-level concentrations were modeled with a second-generation Gaussian-type dispersion model, yielding four dioxin exposure categories. The latter were linked to individual places of residence, using Geographic Information System technology. RESULTS: The risk of developing non-Hodgkin lymphoma was 2.3 times higher (95% confidence interval = 1.4-3.8) among individuals living in the area with the highest dioxin concentration than among those living in the area with the lowest dioxin concentration. No increased risk was found for the intermediate dioxin exposure categories. Adjustment for a wide range of socioeconomic characteristics at the block group level did not alter the results. CONCLUSION: Although emissions from incinerators are usually not regarded as an important source of exposure to dioxins compared with other background sources, our findings support the hypothesis that environmental dioxins increase the risk of non-Hodgkin lymphoma among the population living in the vicinity of a municipal solid waste incinerator.

CD4 cell lymphopenia and atherosclerosis in renal transplant recipients.

Several animal studies suggest that T cell-mediated immunodeficiency may play a role in the progression of atherosclerosis. This study examined the association between lymphocyte subsets and atherosclerotic events in renal transplant recipients. A total of 302 consecutive renal transplant recipients were enrolled in this prospective study. Peripheral blood lymphocyte subsets were quantified and analyzed with respect to other known cardiovascular risk factors. The patients were followed for a mean duration of 23.5 +/- 4.5 mo. Mean CD4, CD8, and CD19 cell levels were 511 +/- 290/mm(3), 553 +/- 596/mm(3), and 66 +/- 62/mm(3), respectively. CD4 levels were positively related to transplant duration (r = 0.32; P = 0.02) and inversely related to age (r = 0.35; P = 0.01). Twenty-five atherosclerotic events (AE) occurred in 25 patients (8.3%). CD4 levels were lower in patients who experienced CVE (288 +/- 170/mm(3) versus 531 +/- 290/mm(3); P < 0.0001). Cox regression analysis showed that patients in the three upper quartiles of CD4 cell count had a decreased risk of CVE compared with those in the lowest quartile. There was a linear increase in risk of CVE with decreasing CD4 cell count (P < 0.0001). A CD4 cell count in the highest quartile (>663/mm(3)) divided the risk of CVE by 10 as compared with the lowest quartile. In conclusion, CD4 lymphocytopenia is an independent risk factor for the development of cardiovascular complications in renal transplant recipients, suggesting that impaired immune response promotes accelerated atherogenesis in this population.

Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: a prospective study.

Renal transplant recipients have disproportionately high rates of arteriosclerotic outcomes, and recent studies provided controlled evidence that clinically stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia. Few studies suggest that hyperhomocysteinemia may be a cardiovascular risk factor in renal transplant recipients. In the study presented here, the association between atherosclerotic events and homocysteine concentrations was examined in 207 stable renal transplant recipients. The role of hyperhomocysteinemia was analyzed with respect to other known cardiovascular risk factors. The mean follow-up was 21.2 +/- 1.9 mo (range, 14 to 26). Mean total homocysteine (tHcy) was 21.1 +/-9.5 micromol/L and median concentration was 19 micromol/L. Seventy percent of patients (n = 153) were hyperhomocysteinemic (values >15 micromol/L). tHcy correlated negatively with folate concentration (r = -0.3; P < 0.01). tHcy was closely related to creatinine concentration (r = 0.54; P < 0.001). Cardiovascular disease events (CVE) including death were observed in 30 patients (14.5 %; 7.34 events per 1000 person-months of follow-up). Fasting tHcy values were higher in patients who experienced CVE (31.5 +/- 10.3 versus 17.8 +/- 7.5; P < 0.001). Cox regression analysis showed that tHcy was a risk factor for cardiovascular complications (relative risk [RR] 1.06; 95% confidence interval (95% CI), 1.04 to 1.09; P < 0.0001). This corresponds to an increase in RR for CVE of 6% per micromol/L increase in tHcy concentration. Age (RR 1.55; 95% CI, 1.09 to 2.19; P < 0.01) and creatinine concentration (RR 1.34; 95% CI, 1.08 to 1.66; P < 0.01) were also independent predictors for CVE. This study demonstrates that elevated fasting tHcy is an independent risk factor for the development of CVE in chronic stable renal transplant recipients. Randomized, placebo-controlled homocysteine studies of the effect of tHcy lowering on CVE rates are urgently required in this patient population.