Abstract
The FAS and FASL system plays a substantial role in apoptosis and immune escape of cells. Three polymorphisms located in the promoter regions of FAS (-1377G/A and -670A/G) and FASL (-844T/C) have been shown to alter the transcriptional activity of the genes, respectively. This study was conducted to evaluate the effects of these polymorphisms on the susceptibility of neuroblastoma in the Chinese population. A total of 203 patients with neuroblastoma and 411 controls were recruited in this case-control study. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was applied for genotyping. Unconditional logistic regression was used to estimate cancer risk by calculating odds ratios (ORs) and their 95% confidence intervals (95% CIs). It was observed that significantly increased risks of neuroblastoma associated with FAS -1377G/A and FASL -844T/C polymorphisms, with ORs equal to 1.55 (95% CI, 1.10–2.20) for FAS -1377 A allele and 2.90 (95% CI, 2.04–4.12) for FASL -844CC genotype carriers compared with non-carriers, respectively. However, no association was found between the polymorphisms of FAS -670A/G and risk of neuroblastoma. In addition, the cumulative effect of FAS and FASL polymorphisms on risk of neuroblastoma was observed (P for trend = 2.502×10−10), with OR for the carriers of both FAS -1377A allele and FASL -844CC genotypes equaled to 3.95 (95% CI, 2.40–6.51). This work reveals that polymorphisms of FAS -1377G/A and FASL -844T/C but not FAS -670A/G are associated with risk of neuroblastoma in Chinese. These findings support the hypothesis that genetic polymorphism in FAS/FASL death system may influence individual susceptibility to neuroblastoma.
Highlights
Neuroblastoma (NB) is a solid tumor derived from primitive sympathetic nervous system that occurs in around 1 in 7000 live births worldwide and accounts for 7–10% of all childhood cancers
For the subjects who carried the combination of FAS -1377A allele and FASL -844CC, the odds ratios (ORs) increased to 3.95. These results demonstrated that the cumulative effect of FAS -1377G/A and FASL -844T/C polymorphisms might increase the risk of NB in this study (P for trend = 2.502610210)
This molecular genetics study examined the association between genetic polymorphisms in apoptotic pathway FAS/FASL system, alone or in combination, and risk of the NB in Chinese population
Summary
Neuroblastoma (NB) is a solid tumor derived from primitive sympathetic nervous system that occurs in around 1 in 7000 live births worldwide and accounts for 7–10% of all childhood cancers. With diverse and dramatic clinical behaviors, though a substantial proportion of affected individuals may have spontaneous regression and favorable clinical outcomes even with no or minimal therapy, most of the older patients have extensive or metastatic disease at the time of diagnosis. Overall prognosis of the latter children has been poor despite of intensive therapy [1,2,3]. Candidate gene approaches have been made to identify several genetic risk factors for NB [13,14,15].
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