Risk factors of neuroblastoma

Summary

As Neuroblastoma (NBL) is an extremely rare cancer, very few studies have been reported that look into the risk factors of NBL. The risk factors associated with NBL include genetic predisposition and familial risk, parental occupational exposure, maternal alcohol consumption, oral contraceptive pills, non-prescription drugs, maternal infection during pregnancy, and allergies or asthma.

Introduction

Neuroblastoma (NBL) is a malignant tumor of the nerve cells. The incidence of NBL peaks in infancy and then halves by the second year of life, with most occurring in infancy. Because NBL is extremely rare, few studies have examined the risk factors for NBL. Some of the risk factors associated with NBL are as follows:

Genetic predisposition and familial risk

Although rare, clustering of neuroblastomas in the family has been reported and is estimated to account for less than 5% of all neuroblastomas. Congenital anomalies occur together in 5% of neuroblastomas​1​. Several genetic alterations have been identified that can lead to the pathogenesis of neuroblastoma. Deletions of the short arm (1p36) on chromosome 1 are a common feature of neuroblastoma tumors, and this region has previously been suggested as a potential candidate for tumor suppressor genes​2​. However, studies suggest another candidate gene at 16p, 2p, 4p and 12p​3​.

Parental occupational exposures

Preliminary studies have shown that the risk for NBL is increased for a number of broad sectors and occupational hazards. Most of them are involved with parents’ occupations such as farming, electronics assembly plant and electrical repairing, leading to speculation about the effects of electromagnetic fields and pesticides. Studies have reported increased pesticide exposure at work in increasing the risk for NBL​4​. It has also been reported occupational hazards lead to a two to three-fold increased risk of NBL with exposure to pesticides, coal tar, some metals, and crude oil​5​.

Maternal alcohol consumption

It is well known that the effects of alcohol on the fetus hinder normal neurological development. Early ethanol exposure may hinder neuronal cell migration and proliferation and lead to neuronal loss. It has also been shown to induce apoptosis in neuronal cell lines. A possible link between alcohol consumption and neuroblastoma has been reported, which explains the development of tumor with fetal alcohol syndrome​3​.

Oral contraceptives or other sex hormones, including fertility hormones 

A study in Germany reported that exposure to oral contraceptives or other sex hormones in early pregnancy quadrupled the risk of NBL in children diagnosed with stage I or II​3​.

Other prescription and non-prescription drugs 

Few other drugs have been studied extensively, and existing studies generally cover a wide range of drug classes. A study has reported a positive association between the disease and the use of prescription painkillers during pregnancy​3​.

Maternal infections in pregnancy

NBL and maternal infection have been studied specifically in some reports. A study reported the link between sexually transmitted diseases (STDs) and NBL​6​. Another study found that vaginal infections were positively associated with neuroblastoma​7​.

Allergies or asthma 

Allergies or asthma status has been found to be negatively associated with other cancers. Studies revealed an inverse association between childhood allergies and the onset of NBL​8​.

References

  1. 1.
    Narod S, Hawkins M, Robertson C, Stiller C. Congenital anomalies and childhood cancer in Great Britain. Am J Hum Genet. 1997;60(3):474-485. https://www.ncbi.nlm.nih.gov/pubmed/9042906
  2. 2.
    Katoh M, Katoh M. Identification and characterization of FLJ10737 and CAMTA1 genes on the commonly deleted region of neuroblastoma at human chromosome 1p36.31-p36.23. Int J Oncol. 2003;23(4):1219-1224. https://www.ncbi.nlm.nih.gov/pubmed/12964007
  3. 3.
    Heck J, Ritz B, Hung R, Hashibe M, Boffetta P. The epidemiology of neuroblastoma: a review. Paediatr Perinat Epidemiol. 2009;23(2):125-143. doi:10.1111/j.1365-3016.2008.00983.x
  4. 4.
    Schüz J, Kaletsch U, Meinert R, Kaatsch P, Spix C, Michaelis J. Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany. J Clin Epidemiol. 2001;54(7):702-709. doi:10.1016/s0895-4356(00)00339-5
  5. 5.
    Kerr M, Nasca P, Mundt K, Michalek A, Baptiste M, Mahoney M. Parental occupational exposures and risk of neuroblastoma: a case-control study (United States). Cancer Causes Control. 2000;11(7):635-643. doi:10.1023/a:1008951632482
  6. 6.
    Hamrick S, Olshan A, Neglia J, Pollock B. Association of pregnancy history and birth characteristics with neuroblastoma: a report from the Children’s Cancer Group and the Pediatric Oncology Group. Paediatr Perinat Epidemiol. 2001;15(4):328-337. doi:10.1046/j.1365-3016.2001.0376a.x
  7. 7.
    Michalek A, Buck G, Nasca P, Freedman A, Baptiste M, Mahoney M. Gravid health status, medication use, and risk of neuroblastoma. Am J Epidemiol. 1996;143(10):996-1001. doi:10.1093/oxfordjournals.aje.a008682
  8. 8.
    Menegaux F, Olshan A, Neglia J, Pollock B, Bondy M. Day care, childhood infections, and risk of neuroblastoma. Am J Epidemiol. 2004;159(9):843-851. doi:10.1093/aje/kwh111