http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16629697

Risk of cancer in children with the diagnosis immaturity at birth

Authors: Mellemkjær, Lene; Hasle, Henrik1; Gridley, Gloria2; Johansen, Christoffer3; Kjær, Susanne K.3; Frederiksen, Kirsten3; Olsen, Jørgen H.3

Source: Paediatric & Perinatal Epidemiology, Volume 20, Number 3, May 2006, pp. 231-237(7)

Publisher: Blackwell Publishing

Abstract:
Summary Mellemkjær L, Hasle H, Gridley G, Johansen C, Kjær SK, Frederiksen K, Olsen JH. Risk of cancer in children with the diagnosis immaturity at birth. Paediatric and Perinatal Epidemiology 2006; 20: 231–237.

Cancer risk in children born before term has been assessed in a large number of case–control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977–89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case–control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case–control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention.

Keywords:  childhood cancer; CNS tumours; preterm; newborn X-rays

Document Type: Research article

DOI: 10.1111/j.1365-3016.2006.00717.x

Affiliations: 1: Department of Paediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark, and 2: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA 3: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen,

Clinical Cancer Research Vol. 12, 2049-2054, April 2006
© 2006 American Association for Cancer Research
Human Cancer Biology

Pediatric Cancers Are Infiltrated Predominantly by Macrophages and Contain a Paucity of Dendritic Cells: a Major Nosologic Difference with Adult Tumors
Jukka Vakkila1,2, Ronald Jaffe3, Marilyn Michelow3 and Michael T. Lotze1

http://clincancerres.aacrjournals.org/cgi/content/abstract/12/7/2049

Authors' Affiliations: 1 Molecular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; 2 Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; and 3 Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Requests for reprints: Jukka Vakkila, Department of Bacteriology and Immunology, Haartman Institute, Haartmaninkatu 31, FIN-00014 University of Helsinki, Helsinki, Finland. Phone: 358-40-821-6939; Fax: 358-10-414-4619; E-mail: jukka.vakkila@mehilainen.fi.

Purpose: Adult cancer is frequently preceded by a period of prolonged chronic inflammation caused by infectious microbial agents or physical or chemical irritants. By contrast, an association between the classic pediatric neoplasias and inflammatory triggers is only rarely recognized. We hypothesized that the difference could be reflected in the inflammatory cell infiltrates of pediatric and adult cancer.

Experimental Design: Three investigators retrospectively studied 27 pediatric and 13 adult cancers at first diagnosis by immunohistochemistry. Inflammatory cells were identified and counted, and their location in relation to tumor tissue was analyzed.

Results: A majority of tumor-associated leukocytes (TAL) in adult tumors were located at the edges of tumor islands forming inflammatory foci between the supporting stroma and the malignant infiltrate. In contrast, TALs in pediatric tumors were scattered within the malignant tumor islands. In adult tumors, TALs were composed of diverse leukocyte types; but in pediatric tumors, the infiltrating cells were predominantly macrophages that accumulated in areas of necrosis within the tumors. The most striking feature in the pediatric tumors was the virtual absence of dendritic cells. The proportion of intratumoral dendritic cells in pediatric samples was 4.1%; whereas in adult tumors, they formed 36.9% of TALs within the tumor islands and 25.1% around the tumors.

Conclusions: We conclude that TALs in pediatric cancers are composed mainly of macrophages and largely devoid of dendritic cell. The findings may provide a major nosologic difference reclassifying pediatric and adult tumors based on nominal inflammatory and noninflammatory etiologies.