ContributorsH

Sara J. Abramson, MD

(e-mail: [email protected]) Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Inge M. Ambros, MD

(e-mail: [email protected]) Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090 Vienna,Austria

Peter F.Ambros, PhD

(e-mail: [email protected]) Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090 Vienna,Austria

Frank Berthold, MD

(e-mail: [email protected]) Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Joseph-Stelzmann-Strasse 9,50924 Cologne, Germany

Garrett M. Brodeur, MD

(e-mail: [email protected]) Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania, Abramson Pediatric Research Center 902, Philadelphia, PA 19104, USA

Irene Y. Cheung, ScD

(e-mail: [email protected])

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Nai-Kong V.Cheung, MD, PhD

(e-mail: [email protected])

Department of Pediatrics, Memorial Sloan-Kettering

Cancer Center, 1275 York Avenue, New York,

NY 10021, USA

Susan L.Cohn, MD

(e-mail: [email protected]) Department of Pediatrics and the Comprehensive Robert H. Lurie Cancer Center, Northwestern University, Feinberg School of Medicine, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA

William L.Gerald, MD

(e-mail: [email protected])

Department of Pathology, Memorial Sloan-Kettering Cancer Center, 275 York Avenue, New York, NY 10021, USA

Stephan A.Grupp, MD, PhD

(e-mail: [email protected])

Director, Stem Cell Biology, Division of Oncology,

Children's Hospital of Philadelphia and University of Pennsylvania,

3615 Civic Center Blvd., ARC 902, Philadelphia,

PA 19104, USA

James Gusney, MD

(e-mail: [email protected]) Division of Pediatric Epidemiology, University of Minnesota, Mayo Mail Code 715, 420 Delaware Street SE, Minneapolis, MN 55455, USA

Daphne A. Haas-Kogan, MD

(e-mail: [email protected]) Department of Radiation Oncology, School of Medicine, University of California at San Francisco, 2356 Sutter Street, San Francisco, CA 94115-0226, USA

Petes J.Houghton, PhD

(e-mail: [email protected]) Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 Lauderdale, Memphis, TN 38105-2794, USA

Kim Kramer, MD

(e-mail: [email protected]) Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Brian H.Kushner, MD

(e-mail: [email protected]) Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Michael P. La Quaglia, MD

(e-mail: [email protected]) Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Caroline Laverdiere, MD

(e-mail: [email protected]) Sainte-Justine Hospital, Recherche Clinique Hemato-Oncologie, 3175 Cote Ste-Catherine, Montreal, Quebec, Canada H3T 1C5

John M. Maris, MD

(e-mail: [email protected])

Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania,

Abramson Pediatric Research Center 902,

Philadelphia, PA 19104, USA

Katherine K.Matthay, MD

(e-mail: [email protected]) Department of Pediatrics, M647, University of California San Francisco School of Medicine, 505 Parnassus, San Francisco, CA 94143-0106, USA

Akira Nakagawara, MD

(e-mail: [email protected]) Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba, 260-8717, Japan

Andrew F.Olshan, MD

(e-mail: [email protected])

Department of Epidemiology,

School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7435, USA

Jennifer K. Peterson, MD

(e-mail: [email protected]) Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 Lauderdale, Memphis, TN 38105-2794, USA

Michael R.Pranzatelli, MD

(e-mail: [email protected]) Departments of Neurology and Pediatrics, National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, P.O. Box 19658, Springfield, IL 62794-9658, USA

C. Patrick Reynolds, MD, PhD

(e-mail: [email protected]) USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology/Oncology MS 57, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90054-0700, USA

Robert A.Ross, PhD

(e-mail: [email protected]) Laboratory of Neurobiology, Department of Biological Sciences, Fordham University, 441 East Fordham Road, Bronx,NY 10458, USA

Manfred Schwab, PhD

([email protected]) German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

Hiroyuki Shimada, MD

(e-mail: [email protected])

Department of Pathology and Laboratory Medicine,

Children's Hospital Los Angeles,

4650 Sunset Boulevard, MS 43, Los Angeles,

CA 90027, USA

Barry L.Shulkin, MD

(e-mail: [email protected]) Department of Radiological Sciences, MS 752, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee, 38105-2794, USA

Thorsten Simon, MD

(e-mail: [email protected]) Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany

Charles A.Sklar, MD

(e-mail: [email protected])

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Paul M.Sondel, PhD

(e-mail: [email protected])

Department of Pediatric Hematology/Oncology,

University of Wisconsin, K4/448,

600 Highland Avenue, Madison, WI 53792, USA

Carol J.Thiele, PhD

(e-mail: [email protected]) Cell and Molecular Biology Section, Center for Cancer Research, NCI, NIH CRC, Room 1-3940,10 Center Drive, MSC-1105, Bethesda, MD 20892-1105, USA

Suzanne L.Wolden, MD

(e-mail: [email protected])

Memorial Sloan-Kettering Cancer Center,

1275 York Avenue, New York, NY 10021, USA

William G.Woods, MD

(e-mail: [email protected]) The Daniel P. Amos Children's Chair for the AFLAC Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta/Emory University, 1405 Clifton Road,Atlanta, GA 30322, USA

Darrell J.Yamashiro, MD

(e-mail: [email protected]) Department of Pediatric Oncology, Irving Pavilion 7,161 Fort Washington Avenue, New York, NY 10032, USA

Epidemiology

Andrew F.Olshan

Contents

1.1 Descriptive Epidemiology 1

1.2 Risk Factors 2

1.2.1 Pregnancy and Childhood Factors 2

1.2.2 Medication Use 3

1.2.3 Lifestyle Exposures 3

1.2.4 Parental Occupation and Environmental Exposures 4

1.3 Conclusions 4

References 5

This chapter reviews the epidemiology of neuroblastoma including the descriptive epidemiology and the evidence for an association with environmental exposures such as parental occupation, medication use during pregnancy, parental smoking and alcohol consumption, pregnancy history, and other exposures.

1.1 Descriptive Epidemiology

In the United States neuroblastoma accounts for 7.2% of all cancers among children younger than 15 years of age (SEER 2003). It is the most common extracranial solid tumor of childhood. Approximately 650 children are diagnosed with neuroblastoma in the United States each year (Goodman et al. 1999).

Based upon 1424 incident cases identified by the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute (NCI) for 1975-2000, the total incidence of neuroblastoma was 10.2 per million children under age 15 years (age-adjusted to the 2000 U.S. standard million population; SEER 2003). The rates were 10.3 per million for males and 10.1 for females. Rates by race and ethnicity were 10.8 for whites, 8.4 for black children, and 7.5 for children of other racial/ethnic groups. The incidence rates by age category were 19.6 per million for ages 1-4 years, 2.9 for ages 5-9 years, and 0.7 for 10-14 years. Neuroblastoma is the most common malignancy among infants (61.3 per million). The incidence rate among infants was slightly higher among males (62.8) than females (59.8).

Based upon international registry data, the incidence of neuroblastoma is highest among Caucasians

Table 1.1. Neuroblastoma survival by gender, race, age, and stage from North American, Europe, Australia, and Israeli Jews (Stiller and Parkin 1992). Lower rates were found for registries in southern and eastern Asia, including India and China, and in Latin America. Over-all,the incidence appeared to be higher for regions or ethnic groups with a higher standard of living (Stiller and Parkin 1992). A previous study by SEER data found no total increase in incidence over time but reported a 3.4% average annual percentage (APC) increase for infants diagnosed between 1973 and 1992 (Gurney et al. 1996). The average annual increase was twice as high for infant boys as for infant girls. Other studies in the United States and elsewhere have noted increases in the incidence of neuroblastoma (Olshan and Bunin 2000). Improvements in diagnostic procedures, prenatal diagnosis, and possibly screening in some countries contributed to some of the increase during the 1970s through the early 1990s; however, analysis of the most recent SEER data (1973-2000) showed no significant increase in incidence overall (annual percentage change=0.3%) or among infants

(APC=0.7%). There is some variability in 5-year relative survival rates based on age and stage (Table 1.1). Based upon SEER data for the years 1985-2000 the 5-year relative survival rate for neuroblastoma was 65%. No overall differences were found by race or gender. Survival was highest among infants and those with local or regional disease. Poorer survival was found for older children and those with distant metastases disease.

1.2 Risk Factors

The odds ratio provides an estimate of the relative risk, the risk among those with the exposure relative to the risk among those without the exposure. The odds ratio is estimated using exposure data collected in a case-control study, an efficient study design for a rare disease such as neuroblastoma. Odds ratios above the null value of 1.0 (indicating no case-control differences in the prevalence of a given exposure or factor) suggest a positive association, whereas odds ratios below 1.0 suggest that the factor may be associated with decreased risk. The assessment of the statistical associations should also include consideration of study design and analysis issues, such as the role of chance, confounding variables, and selection and exposure misclassification bias. Except where specifically indicated, the majority of epidemiologic studies have not examined any potential heterogeneity in risk among neuroblastoma subgroups defined by stage, age, or molecular markers.

1.2.1 Pregnancy and Childhood Factors

Several epidemiologic studies have investigated the role of reproductive history and birth characteristics in the etiology of neuroblastoma (See Review by Olshan and Bunin 2000). Conflicting results have been found for risk of neuroblastoma and maternal history of prior miscarriage, history of one or more induced abortions (Hamrick et al. 2001; Buck et al. 2001), repeat Cesarean birth and history of vaginal infection during pregnancy and sexually transmitted infection (Michalek et al. 1996; Hamrick et al. 2001). Studies also conflict with regard to the relationship

Table 1.1. Neuroblastoma survival by gender, race, age, and stage

5-year relative survival rate (%)a

Male

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