Spatial clustering of childhood cancers in Switzerland: a nationwide study

Purpose

Childhood cancers are rare and little is known about their etiology. Potential risk factors include environmental exposures that might implicate spatial variation of cancer risk. Previous studies of spatial clustering have mainly focused on childhood leukemia. We investigated spatial clustering of different childhood cancers in Switzerland using exact geocodes of place of residence.

Methods

We included 6,034 cancer cases diagnosed at age 0–15 years during 1985–2015 from the Swiss Childhood Cancer Registry. Age and sex-matched controls (10 per case) were randomly sampled from the national censuses (1990, 2000, 2010). Geocodes of place of residence were available at birth and diagnosis for both cases and controls. We used the difference in k-functions and Cuzick–Edwards test to assess global clustering and Kulldorff’s circular scan to detect individual clusters. We also carefully adjusted for multiple testing.

Results

After adjusting for multiple testing, we found no evidence of spatial clustering of childhood cancers neither at birth (p?=?0.43) nor diagnosis (p?=?0.13). Disregarding multiple testing, results of individual tests indicated spatial clustering of all childhood cancers combined (p?<?0.01), childhood lymphoma (p?=?0.01), due to Hodgkin lymphoma (HL) (p?=?0.02) at diagnosis, and embryonal tumors of the central nervous system (CNS) at birth and diagnosis, respectively (p?=?0.05 and p?=?0.02).

Conclusions

This study provides weak evidence of spatial clustering of childhood cancers. Evidence was strongest for HL and embryonal CNS tumors, adding to the current literature that these cancers cluster in space.

     

Physiological effects of polychlorinated biphenyls or a combination of DDT,DDD, and DDE in penned white pelicans

The effects of PCBs (polychlorinated biphenyls) or a combination of DDT (1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane), DDD (1,1-dichloro-2,2-bis (p-chlorophenyl) ethane) and DDE (1,1-dichloro-2,2-bis (p-chlorophenyl ethylene) on organ weights, liver storage of vitamin A and carotene, selected blood chemistry parameters, and serum protein fractions were determined in penned white pelicans (Pelecanus erythrorhynchos) receiving a daily dosage of these compounds. Birds received 100 mg of PCBs or a combination of DDT (20 mg), DDD (15 mg), and DDE (15 mg) injected into the first fish fed each day for ten weeks. A greater percentage of PCB treatment was retained in brain, liver, carcass and feathers than the percentage of DDT + DDD + DDE treatment. Liver weight as percent of body weight decreased (p<0.01) in DDT + DDD + DDE-treated birds and increased (p<0.01) as a total weight in PCB-treated birds. Spleen weight as percent of body weight was greater (p<0.05) in PCB-treated birds. Neither treatment had a significant effect on the weight of the brain, heart, or kidney. Liver vitamin A levels were greater (p<0.01) on a g/g of liver basis in the DDT-treated birds than in controls. Significant lowering of serum potassium and protein values was noted in both the PCB- and the combination of DDT, DDD, DDE-treated birds, while serum calcium values were lowered (p<0.01) only in PCB-treated birds. Values of serum inorganic phosphorus, uric acid and magnesium were not significantly changed by either treatment. Globulin fractions were unaltered by either treatment, but albumin fractions were lowered (p<0.01) in the PCB-treated pelicans.     

Acquired immune dysfunction in homosexual men: immunologic profiles

Homosexual men with Kaposi sarcoma, lymphadenopathy syndrome, opportunistic infection, and nonhomosexual traditional Kaposi sarcoma were evaluated for B cell, T cell, and complement immunity and compared to normal controls and homosexual controls. No significant immunologic abnormalities were found in the traditional Kaposi group. All homosexual groups, including the homosexual controls, had a significant decrease in the helper/suppressor cell ratio. Functional abnormalities of T-cell immunity were observed in the homosexual Kaposi sarcoma, lymphadenopathy syndrome, and opportunistic infection groups. Significant elevations of IgG, IgM, IgA, and IgE were found in the lymphadenopathy group, while only IgG and IgA were elevated in the Kaposi sarcoma group. C3, C4, and immune complexes were normal, while total hemolytic complement activity was increased in the Kaposi sarcoma and lymphadenopathy syndrome groups.     

Impaired mononuclear-cell proliferation in patients with the acquired immune deficiency syndrome results from abnormalities of both T lymphocytes and adherent mononuclear cells

Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome proliferate poorly after stimulation with soluble mitogens. The present study was undertaken to assess the relative contributions of T lymphocytes and of plastic adherent mononuclear cells to the impaired mononuclear cell responses. We employed a four-step separation procedure including terminal depletion using a monocyte-specific monoclonal antibody (61D3) to derive populations of highly purified T cells from patients and from normal subjects. Highly purified T cells proliferated poorly in response to phytohemagglutinin and pokeweed mitogen. The addition of autologous adherent cells to highly purified T cells markedly improved mitogen-driven proliferation in all subjects; however, mononuclear cells from patients with AIDS responded less well than normals (P0.01) for both phytohemagglutinin and pokeweed. Allogeneic normal adherent cells fully restored both phytohemagglutinin and pokeweed responses in normal highly purified T cells. Adherent cells from patients were comparable to normal adherent cells in phytohemagglutinin-driven proliferation but performed significantly less well when pokeweed was used to stimulate normal highly purified T-cell responders (4308 cpm after coculture with patients' adherent cells vs 8244 cpm after coculture with allogeneic normal adherent cells;P=0.05). Similarly, when patient's highly purified T cells were stimulated with pokeweed mitogen, control adherent cells functioned substantially better than patient adherent cells (1198 cpm for allogeneic patient adherent cells vs 2324 cpm for normal adherent cells;P=0.05). Although the addition of normal adherent cells to patients' highly purified T cells significantly improved pokeweed mitogen responses, these values did not reach normal. Suppression by patients adherent cells was not demonstrated. Abnormal mitogen responses in acquired immunodeficiency appear to be primarily a result of an intrinsic T-lymphocyte disorder. This defect cannot be correctedin vitro by coculture with normal adherent cells. Adherent mononuclear cells from patients with acquired immunodeficiency supported phytohemagglutinin responses as well as normal adherent cells. However, patients' adherent cells showed decreased accessory function when pokeweed mitogen was employed to stimulate responder cells. These data suggest that abnormalities of adherent mononuclear cells are present in patients with acquired immunodeficiency and that this defect may contribute to the impaired mitogen responses in these patients. Pokeweed mitogen assays are particularly sensitive in demonstrating abnormal accessory-cell function.The opinions and assertions expressed herein are those of the authors and are not to be construed as official or as reflecting the views of the Navy Department or of the Naval Service at large.     

Dietary protein deficiency induces osteoporosis in aged male rats.

Low dietary intake is common in elderly males with low femoral neck areal bone mineral density (BMD). To evaluate the selective influence of a low-protein diet in the pathogenesis of osteoporosis in males and to uncover early and late adaptation of bone cells to protein deficiency, 8-month-old male rats were pair-fed a control (15% casein) or isocaloric low-protein (2.5% casein) diet for 1 or 7 months. BMD, bone ultimate strength, stiffness, and absorbed energy were measured in tibia proximal metaphysis and diaphysis. After double-labeling, histomorphometric analysis was performed at the same sites. Serum osteocalcin, insulin-like growth factor I (IGF-I), and urinary deoxypyridinoline excretion were measured. In proximal tibia, isocaloric low-protein diet significantly decreases BMD (12%), cancellous bone mass (71%), and trabecular thickness (Tb.Th; 30%), resulting in a significant reduction in ultimate strength (27%). In cortical middiaphysis, a low-protein diet decreases BMD (9%) and enlarges the medullary cavity (36%), leading to cortical thinning and lower mechanical strength (20%). In cancellous bone, protein deficiency transiently depresses the bone formation rate (BFR; 60%), osteoid seam thickness (15%), and mineral apposition rate (MAR; 20%), indicating a decrease in osteoblast recruitment and activity. Cortical loss (15%) results from an imbalance between endosteal modeling drifts with impaired BFR (70%). From the first week of protein deficiency, osteocalcin and IGF-I levels drop significantly. Bone resorption activity and urinary deoxypyridinoline remain unchanged throughout the experiment. Protein deficiency in aged male rats induces cortical and trabecular thinning, and decreases bone strength, in association with a remodeling imbalance with a bone formation impairment and a decrease in IGF-I levels.