Based on SEER (www.seer.cancer.gov) registry data 19852000
Based on SEER (www.seer.cancer.gov) registry data 19852000
between preterm birth (<37 weeks gestation) and low birth weight (<2500 g). One study reported that neuroblastoma patients were less likely than controls to have been born preterm (Johnson and Spitz 1985); however, a trend toward increasing risk with lower birth weight was observed among term births. Two recent studies have reported positive associations: one with very preterm birth (<33 weeks odds ratio=1.9; Hamrick et al. 2001); and preterm birth among patients with stage-3 or stage-4 neuroblastoma (odds ratio=3.4; Schuz et al. 2001). Low birth weight and very low birth weight (<1500 g) have been found to increase risk in two studies (Johnson and Spitz 1985; Hamrick et al. 2001). Two studies have reported no differences in birth weight or gestational age, and no associations with birth order, maternal age, or parity have been reported (Hamrick et al. 2001).
A German study reported that a history of tonsillectomy and/or appendectomy increased the risk threefold for stage-3 or stage-4 neuroblastoma patients (Schuz et al. 2001). Breastfeeding for more than 6 months was shown to decrease the risk of neuroblastoma by 40% in one study (Daniels et al. 2002).
A recent review indicated that some studies have found a significant excess of birth defects among children with neuroblastoma compared directly with controls or using expected rates (Foulkes et al. 1997). Associations with defects, including neurofibromato-sis type 1, Beckwith-Wiedemann syndrome, Hirschsprung's disease, musculoskeletal and cardiovascular malformations, Turner's syndrome, and neurodevel-opmental abnormalities, have been reported. Some of these associations were not consistent across studies, and over- or under-ascertainment could bias the comparisons. Molecular studies of familial neuroblastoma cases have not provided evidence of linkage with the genes thought to be responsible for Hirschsprung's disease or neurofibromatosis (Maris et al. 1997).
Case series reports from Israel, Australia, and Japan identified a possible relationship with maternal use of hormones for bleeding,history of miscarriage, and ovulation induction (see review by Olshan and Bunin 2000). Four case-control studies have examined hor mone use before or during pregnancy. Positive associations (odds ratio>2.0) have been reported with maternal use of sex hormones 3 months prior to or during pregnancy and among women with a history of miscarriage or stillbirth. Indications for hormone usage included contraception, vaginal bleeding, and previous miscarriage. The largest case-control study (504 cases) found no overall association with infertility, infertility treatment, and other hormone use, although an elevated risk (odds ratio=4.4) was found for Clomid use among male offspring, consistent with a previous finding (Olshan et al. 1999a). Other maternal medications used during pregnancy that have been found in some studies to increase the risk of neuroblastoma include a group termed "neurally active" drugs (amphetamines, antidepressants, an-tipsychotics, muscle relaxants, prescription pain medications, and tranquilizers), antinauseants, diuretics, analgesics, and antibiotics (odds ratio=2.8; Kramer et al. 1987).
A recent report suggested that maternal multivitamin use during pregnancy was associated with a 30-40% reduction in the risk of neuroblastoma (Olshan et al. 2002). The analysis was unable to isolate any specific vitamin that might be responsible for the association. The finding requires replication in epi-demiologic studies and possible investigation in laboratory experiments.
Although a possible increased risk exists for mother's smoking during pregnancy, other studies have failed to confirm this finding (Olshan and Bunin 2000; Yang et al. 2000). No association with paternal smoking has been found. A possible association between fetal alcohol syndrome and neuroblastoma has been reported (Kinney et al. 1980). Case-control studies have not reported a difference in the proportion of case and control mothers who reported alcohol consumption during pregnancy; however, daily drinking or drinking three or more drinks on one occasion was associated with a nine- and sixfold elevated risk, respectively (Kramer et al. 1987). Other studies have not found an association with the amount or frequency of alcohol consumption.
1.2.4 Parental Occupation and Environmental Exposures
Parental occupation, specifically paternal occupation, has been found to increase the risk of neuroblastoma in offspring in several studies (Olshan and Bunin 2000; Olshan et al. 1999b; DeRoos et al. 2001a-c). Two of the studies found an association with fathers employed in electronics-related occupations including electricians, electric and electronics workers, electrical equipment assembly, linemen, utility employees, welders, and electric equipment salesmen and repairmen. The risk estimates were relatively large (>2.0) but imprecise. Other paternal occupations and industries that had an increased risk included food product packers and warehouse men, farmers and agricultural workers, rubber processing, painting, chemistry occupations, tire manufacturing, rubber/plastics/synthetics industry, service occupations, packaging and materials handling, and processing occupations.
Bunin et al. (1990) reported an increased risk (odds ratio=2.2) for maternal occupations including stock girls, textile and food product packers, plastic product packers, electrical products assembly, and metal product fabrication workers. Parental occupational exposures reported to be associated with risk included dusts, aromatic and aliphatic hydrocarbons, electromagnetic fields, metal fumes and dusts, benzene, asbestos, and pesticides/herbicides. The studies did not include direct measurement of occupational exposures but indirectly inferred the potential exposures using job title and industry.
All the parental occupation studies thus far have a number of limitations including the lack of a complete occupational history in studies using birth certificates, broad occupational groupings, crude exposure assessment, and small sample sizes. Nonetheless, the current epidemiologic evidence suggests that the risk of several occupations (e.g., electronics-related jobs) warrants further evaluation.
Two studies have reported associations with self-reported use of home and garden pesticides (Daniels et al. 2001; Schuz et al. 2001). One study reported a twofold increased risk for garden pesticides among children with stage-3 or stage-4 disease (Schuz et al.
2001). Another study did not find any differences in risk among subgroups defined by MYCN tumor status or stage (Daniels et al. 2001). There have been reports of "clusters" of neuroblastoma cases in communities in the United States. Environmental factors, such as proximity to hazardous waste sites,have been suggested as possibly related to the etiology of these clusters, but firm evidence to confirm the causality of these speculative associations has been consistently lacking.
Several epidemiologic studies have been conducted to evaluate potential risk factors for neuroblastoma. No causal factor(s) has been isolated. Few of the reported associations have been replicated in multiple studies. Moreover, the studies have suffered from methodologic limitations such as small sample size (most studies had fewer than 200 cases), incomplete exposure data collection, and inadequate control groups.
Despite these limitations, the previous studies have provided leads that warrant evaluation in future studies. Certain pregnancy and birth factors, parental occupation, and medications deserve more careful investigation. Besides addressing the methodologic concerns outlined above, future studies should take advantage of the developments in molecular epidemiology and identification of specific genetic variation in the human genome. The sharp distinction between favorable (local reginal-4S) and high-risk (stage 4 and MCYN-amplified stage 3) groups, as well as apparent biologic heterogeneity of neuroblas-toma, should be incorporated directly in future epi-demiologic studies. Biologic subgroups that represent different etiologic pathways for neuroblastoma can refine our ability to detect risk factors operating in those pathways. Finally, the incorporation of genetic susceptibility factors, such as common polymorphisms for genes involved in carcinogen metabolism and DNA repair, may help elucidate gene-environment interactions that have otherwise gone undetected with only the exposure data.
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A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.