Research Paper Volume 9, Issue 3 pp 852—859
The TP53 gene rs1042522 C>G polymorphism and neuroblastoma risk in Chinese children
- 1 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
- 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China
- 3 Molecular Epidemiology Laboratory and Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China
Received: December 22, 2016 Accepted: March 3, 2017 Published: March 8, 2017
https://doi.org/10.18632/aging.101196How to Cite
Abstract
TP53, a tumor suppressor gene, plays a critical role in cell cycle control, apoptosis, and DNA damage repair. Previous studies have indicated that the TP53 gene Arg72Pro (rs1042522 C>G) polymorphism is associated with susceptibility to various types of cancer. We evaluated the association of the TP53 gene rs1042522 C>G polymorphism with neuroblastoma susceptibility in a hospital-based study among the Chinese Han population. Enrolled were 256 patients and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) generated using logistic regression models were used to determine the strength of the association of interest. No association was detected between rs1042522 C>G polymorphism and neuroblastoma risk. In our stratification analysis of age, gender, sites of origin, and clinical stages, we observed that subjects with rs1042522 CG/GG genotypes had a lower risk of developing neuroblastoma in the mediastinum (Adjusted OR=0.52, 95% CI=0.33-0.82, P=0.005) than those carrying the CC genotype. These results indicate that TP53 gene rs1042522 C>G polymorphism may exert a weak and site-specific effect on neuroblastoma risk in Southern Chinese children and warrant further confirmation.
Introduction
Neuroblastoma, a common pediatric solid tumor, accounts for about 10% of all childhood cancers, and is the third leading cause of cancer-related death in children [1]. The incidence rate of neuroblastoma is relatively low, approximately affecting 7.7 live births per million in China [2]. However, incidence is higher in Europe and the United States, with 8-14 cases per million [3]. Neuroblastoma is a cancer of the sympathetic nervous system with diverse clinical phenotypes [4]. A substantial proportion of neuroblastomas are localized benign tumors that can spontaneously regress and thus patients bearing these tumors may have a favorable prognosis [5]. However, approximately 50% of patients show an aggressive clinical course with a survival rate of less than 35% despite aggressive therapy [4,6].
The exact etiology and pathogenesis of neuroblastoma remains unknown [7]. It has been reported that offspring can be more susceptible to neuroblastoma if the parents were exposed to risk factors such as wood dust, radiation sources, and hydrocarbons [8,9]. On the contrary, parental exposure to risk factors alone cannot explain the phenomenon that only a small portion of affected offspring develops neuroblastoma. Growing evidence indicates that genetic polymorphisms increase predisposition to neuroblastoma [10,11]. In addition to genome-wide association studies (GWASs), candidate gene approaches have also been applied to identify potential variants associated with neuroblastoma. Indeed, several neuroblastoma predisposition genes have been discovered, including FAS [12], FASL [12], NEFL [11], TGFBR3L [13], XPG [14] and XPC [15].
Tumor suppressor gene TP53 is located on chromosome 17p13. p53, a protein encoded by the TP53 gene, plays a pivotal role in cell cycle control, apoptosis, senescence, and maintenance of DNA integrity [16–18] by regulating the expression of many genes including p21, PUMA, DRAM, and MDM2, among others [19]. The TP53 gene is one of the most frequently mutated genes in human cancers [16,20–23]. More than 200 single nucleotide polymorphisms (SNPs) have been reported in the TP53 gene [22]. A non-synonymous polymorphism leading to the substitution of proline for arginine (Arg72Pro) at codon 72 of the p53 protein was discovered in the TP53 gene (rs1042522 G>C) [24]. Multiple studies have been performed among populations of different ethnic background to investigate the association between this functional TP53 polymorphism and the risk of many cancers, including cervical cancer, colorectal cancer, breast cancer, lung cancer, ovarian cancer, and endometrial cancer [25–29]. However, few studies have focused on neuroblastoma. Here, we performed a hospital-based case-control study using data from 256 neuroblastoma patients and 531 control subjects to evaluate the association between the TP53 gene rs1042522 G>C polymorphism and neuroblastoma risk in Southern Chinese children.
Results
Population characteristics
Our research population consisted of 256 neuroblastoma patients and 531 cancer-free controls. The demographic characteristics of all participants are shown in Supplemental Table 1. There was no significant difference in age (P=0.239) nor gender (P=0.333) between cases and controls. Regarding the sites of tumor origin, 46 (17.97%), 87 (33.98%), 90 (35.16%), 25 (9.77%) neuroblastomas occurred in adrenal glands, retroperitoneal region, mediastinum, and other regions, respectively, while the origin of eight (3.13%) neuroblastomas was not determined because of the limited availability of tumor samples. Moreover, according to the INSS criteria [30], 54 (21.09%), 65 (25.39%), 44 (17.19%), 77 (30.08%), and nine (3.52%) cases were classified into stage I, II, III, V, and 4s disease, respectively, with an exception of seven cases (2.73%) classified into NA (not available) due to lack of information.
TP53 gene rs1042522 C>G polymorphism with neuroblastoma risk
The frequency of occurrence of the TP53 gene rs1042522 C>G genotype in cases and controls, as well as the associations with neuroblastoma risk, are listed in Table 1. Our observations agree with Hardy-Weinberg equilibrium conditions (P=0.440) among the controls. The genotype frequency distribution of the TP53 gene rs1042522 C>G polymorphism was as follows: 35.55% (CC), 42.19% (CG) and 22.27% (GG) in the patients and 29.25% (CC), 48.11% (CG) and 22.64% (GG) in the controls. No association between the rs1042522 C>G polymorphism and neuroblastoma risk was observed, even when age and gender were adjusted for.
Table 1. Genotype distributions of TP53 gene rs1042522 C>G polymorphism and neuroblastoma susceptibility
| Genotype | Cases (N=256) | Controls (N=530) | Pa | Crude OR (95% CI) | P | Adjusted OR (95% CI) b | Pb | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| rs1042522 (HWE=0.440) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CC | 91 (35.55) | 155 (29.25) | 1.00 | 1.00 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CG | 108 (42.19) | 255 (48.11) | 0.72 (0.51-1.02) | 0.062 | 0.72 (0.51-1.02) | 0.065 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| GG | 57 (22.27) | 120 (22.64) | 0.81 (0.54-1.22) | 0.309 | 0.80 (0.53-1.21) | 0.290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additive | 0.175 | 0.88 (0.72-1.08) | 0.229 | 0.88 (0.72-1.08) | 0.215 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dominant | 165 (64.45) | 375 (70.75) | 0.076 | 0.75 (0.55-1.03) | 0.075 | 0.75 (0.55-1.03) | 0.074 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Recessive | 199 (77.73) | 410 (77.36) | 0.906 | 0.98 (0.68-1.40) | 0.906 | 0.97 (0.68-1.39) | 0.860 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OR, odds ratio; CI, confidence interval, HWE, Hardy-Weinberg equilibrium. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| aχ2 test for genotype distributions between neuroblastoma patients and controls. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| b Adjusted for age and gender. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Stratification analysis
We further explored the association between rs1042522 C>G polymorphism and neuroblastoma susceptibility stratifying by age, gender, tumor sites, and clinical stages. As shown in Table 2, when compared with the CC genotype, the CG/GG genotypes of the rs1042522 C>G polymorphism were associated with a decreased risk of developing neuroblastoma in mediastinum [adjusted odds ratio (OR) =0.52, 95% confidence interval (CI)=0.33-0.82, P=0.005]. Moreover, we also observed a borderline significant protective association between the rs1042522 C>G polymorphism and neuroblastoma risk in males (adjusted OR=0.66, 95% CI=0.44-1.00, P=0.051). No other significant associations were detected.
Table 2. Stratification analysis for the association between TP53 gene rs1042522 C>G polymorphism and neuroblastoma susceptibility
| Variables | rs1042522 (cases/controls) | Crude OR | P | Adjusted OR a | Pa | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CC | CG/GG | (95% CI) | (95% CI) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Age, month | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ≤18 | 36/68 | 65/165 | 0.74 (0.45-1.22) | 0.242 | 0.74 (0.45-1.21) | 0.229 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| >18 | 55/87 | 100/210 | 0.75 (0.50-1.14) | 0.179 | 0.76 (0.50-1.14) | 0.186 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gender | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Females | 34/71 | 69/161 | 0.90 (0.55-1.47) | 0.661 | 0.89 (0.54-1.47) | 0.649 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Males | 57/84 | 96/214 | 0.66 (0.44-1.00) | 0.0499 | 0.66 (0.44-1.00) | 0.051 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sites of origin | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adrenal glands | 13/155 | 33/375 | 1.05 (0.54-2.05) | 0.888 | 1.04 (0.53-2.04) | 0.906 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retroperitoneal | 29/155 | 58/375 | 0.83 (0.51-1.34) | 0.440 | 0.82 (0.51-1.34) | 0.430 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mediastinum | 40/155 | 50/375 | 0.52 (0.33-0.82) | 0.005 | 0.52 (0.33-0.82) | 0.005 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other | 7/155 | 18/375 | 1.06 (0.44-2.60) | 0.894 | 1.06 (0.43-2.59) | 0.899 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical stages | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| I+II+4s | 44/155 | 75/375 | 0.70 (0.46-1.07) | 0.099 | 0.71 (0.47-1.07) | 0.104 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| III+IV | 40/155 | 81/375 | 0.84 (0.55-1.28) | 0.409 | 0.84 (0.55-1.28) | 0.417 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OR, odds ratio; CI, confidence interval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| a Adjusted for age and gender, omitting the corresponding stratification factor. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Discussion
In our hospital-based case-control study here, we explored the relationship between the TP53 gene rs1042522 C>G polymorphism and neuroblastoma susceptibility. However, we did not detect a main effect on neuroblastoma susceptibility for the rs1042522 C>G polymorphism. Overwhelming evidence suggests that the TP53 gene is a crucial tumor suppressor. Disruption or abnormally low transcription of the TP53 gene can impair the tumor-suppressing function of the p53 signaling pathway, thereby promoting tumor development and progression [20]. The TP53 gene is the most frequently mutated gene in many human cancers [31,32]. The TP53 gene rs1042522 C>G polymorphism in exon 4 results in a non-conservative transversion of arginine (Arg) to proline (Pro) at codon 72 [33]. It is the most commonly studied genetic variant in the TP53 gene, and its implications in cancer genetic epidemiology have been amply documented [34–36]. Previous functional analyses indicated that the two alleles of the TP53 gene have differential capacities to regulate various cellular functions. For example, the p53 codon 72 Pro variant exhibits a markedly reduced capacity to induce apoptosis compared to wild-type p53 due to decreased mitochondria localization [37], but an increased efficiency in the induction of cell cycle arrest [38].
Several studies have indicated that the TP53 gene rs1042522 C>G polymorphism might promote tumor development; however, consensus has not been reached. Khan et al. genotyped 140 thyroid cancer patients and 200 cancer-free controls from Kashmir Valley to evaluate the association between the TP53 gene rs1042522 C>G polymorphism and the risk of differentiated thyroid cancer [38]. They found that rs1042522 C>G polymorphism conferred higher susceptibility to thyroid cancer [39]. In a study conducted among the Bangladeshi population including 50 histopathologically confirmed lung cancer patients and 50 age-matched controls, Chowdhury et al. found that the TP53 gene rs1042522 CC genotype is a risk factor for lung cancer [40]. Wu et al. also suggested that there is an increased risk of gastric cancer for individuals with the TP53 gene rs1042522 C>G polymorphism among the Chinese Han population [41]. However, in another case-control study analyzing the association between the TP53 gene rs1042522 C>G polymorphism and retinoblastoma risk in the Chinese Han population, Chen et al. found that no in allele or genotypic frequencies of the TP53 gene rs1042522 C>G between cases (n=168) and controls (n=185) [42].
Although many studies have been carried out to investigate the association between the TP53 gene rs1042522 C>G polymorphism and the risk of various cancers, only two of them addressed neuroblastoma. Cattelani et al. conducted the first of these studies in a population of European descent. They found that the TP53 gene rs1042522 C>G polymorphism had no impact on the risk of developing neuroblastoma in 288 healthy subjects and 286 neuroblastoma patients [43]. By analyzing three independent case-control cohorts comprising 10,290 individuals, Diskin et al. found that the TP53 gene rs78378222 A>C and rs35850753 A>G polymorphisms were robustly associated with neuroblastoma risk. However, they failed to detect any association between the TP53 gene rs1042522 C>G variant and overall survival in 1,809 neuroblastoma patients [44]. In addition, very few studies have found a relationship between other polymorphisms in the TP53 gene and neuroblastoma risk. E.g., Rihani et al. investigated the impact of rs1042522 C>G and rs78378222 A>C in the TP53 gene, but failed to detect any significant relationship with neuroblastoma risk [45].
Our current study shows that the rs1042522 C>G polymorphism might not affect the susceptibility to neuroblastoma in most patients. However, more studies are needed to further substantiate our negative observation due to multiple factors limiting our study. For example, our study could not have detected the possible mild effects of low-penetrating genetic variants because of our small sample size due to the low incidence of this disease. Indeed, the modest association we measured between the rs1042522 C>G polymorphism and neuroblastoma risk in the mediastinum subgroup may be attributable to the relatively small sample size of this study. Furthermore, some susceptibility alleles in single genes may moderately contribute to neuroblastoma risk. In addition, neuroblastoma is a multi-factorial disease resulting from multiplicative interactions between environmental factors and genetic backgrounds. Our study lacked information on some valuable parameters, such as parental exposures, dietary intake, and living environment. Indeed, interacting factors, such as environmental exposures or interfering genes (MDM2, MDM4 and Hausp), may override the effects of the rs1042522 C>G polymorphism [46]. Furthermore, selection bias might also exist, since our study was a hospital-based study with subjects recruited from southern China; therefore, our study population might not be representative of the genera Chinese population. Finally, only the rs1042522 C>G polymorphism was included in this study. However, it is clear that only a small proportion of SNPs can influence cancer susceptibility (driver mutation), while most of them cannot (passenger mutations) [47]. Therefore, discovering or discarding any potential influence of the rs1042522 C>G polymorphism on neuroblastoma susceptibility requires further studies with larger populations, including other functional SNPs. Nonetheless, our study is the largest analyzing the correlation between the TP53 gene rs1042522 C>G polymorphism and neuroblastoma risk among the Chinese population. We found that the TP53 gene rs1042522 C>G polymorphism had no main effect on neuroblastoma susceptibility. However, since the effect of this polymorphism might be influenced by site and sex, further prospective, large-scale, multicenter studies involving populations of different ethnicities are required to strengthen our findings.
Materials and Methods
Study subjects
The subjects recruited were described in previous studies [14,48–50]. Briefly, all of them were genetically unrelated ethnic Han Chinese from southern China. This study included 256 patients with newly diagnosed and histologically confirmed neuroblastoma and 531 cancer-free controls. The current study was approved by the Institutional Review Board of Guangzhou Women and Children’s Medical Center. Informed written consent was obtained from participants’ parents or their legal guardians.
Genotyping by Taqman
The TP53 gene rs1042522 C>G was genotyped by using Taqman real-time PCR on a 7900 Sequence Detection System (Applied Biosystems, Foster City, CA), as previously described [51–53]. For quality control purposes, eight duplicate positive controls and eight negative controls without DNA were used in each of 384-well plates.
Statistical analysis
Goodness-of-fit χ2 test was performed to test for deviations from Hardy-Weinberg equilibrium in genotype frequencies of the polymorphism in controls. Two-sided χ2 test was used to evaluate the differences in demographic variables and frequency distributions of genotype between patients and controls. We conducted unconditional univariate logistic regression to estimate the association between the TP53 gene rs1042522 C>G polymorphism and neuroblastoma susceptibility by computing ORs and 95% 95% CIs. Adjusted ORs were calculated using multivariate analysis adjusting for age and gender. All statistical analyses were performed using SAS software (version 9.1; SAS Institute, Cary, NC). P < 0.05 was considered as statistically significant.
Supplementary Materials
Supplementary File
Acknowledgements
We thank Yanlu Tong, Hezhen Wang and Hongjiao Chen for their assistance with DNA extraction and medical histories information collection.
Conflicts of Interest
There are no competing interests to declare.
Funding
This study was supported by the grants from the National Natural Science Foundation of China (No. 81502046), the State Clinical Key Specialty Construction Project (Pediatric Surgery) 2013 (No: GJLCZD1301), the Clinical Medicine Research and Transformation Center of Brain Injury in Premature Infants in Guangzhou (No: 520101-2150092), and the Guangzhou Science Technology and Innovation Commission (No: 201607010395).
References
- 1. Smith MA, Seibel NL, Altekruse SF, Ries LA, Melbert DL, O’Leary M, Smith FO, Reaman GH. Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol. 2010; 28:2625–34. https://doi.org/10.1200/JCO.2009.27.0421 [PubMed]
- 2. Bao PP, Li K, Wu CX, Huang ZZ, Wang CF, Xiang YM, Peng P, Gong YM, Xiao XM, Zheng Y. [Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010]. Zhonghua Er Ke Za Zhi. 2013; 51:288–94. Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010 [PubMed]
- 3. Moreno F, Lopez Marti J, Palladino M, Lobos P, Gualtieri A, Cacciavillano W. Childhood Neuroblastoma: Incidence and Survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA Network 2000-2012. Pediatr Blood Cancer. 2016; 63:1362–67. https://doi.org/10.1002/pbc.25987 [PubMed]
- 4. Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet. 2007; 369:2106–20. https://doi.org/10.1016/S0140-6736(07)60983-0 [PubMed]
- 5. Hero B, Simon T, Spitz R, Ernestus K, Gnekow AK, Scheel-Walter HG, Schwabe D, Schilling FH, Benz-Bohm G, Berthold F. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol. 2008; 26:1504–10. https://doi.org/10.1200/JCO.2007.12.3349 [PubMed]
- 6. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shimada H, Black CT, Brodeur GM, Gerbing RB, Reynolds CP, and Children’s Cancer Group. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med. 1999; 341:1165–73. https://doi.org/10.1056/NEJM199910143411601 [PubMed]
- 7. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010; 362:2202–11. https://doi.org/10.1056/NEJMra0804577 [PubMed]
- 8. De Roos AJ, Teschke K, Savitz DA, Poole C, Grufferman S, Pollock BH, Olshan AF. Parental occupational exposures to electromagnetic fields and radiation and the incidence of neuroblastoma in offspring. Epidemiology. 2001; 12:508–17. https://doi.org/10.1097/00001648-200109000-00008 [PubMed]
- 9. De Roos AJ, Olshan AF, Teschke K, Poole C, Savitz DA, Blatt J, Bondy ML, Pollock BH. Parental occupational exposures to chemicals and incidence of neuroblastoma in offspring. Am J Epidemiol. 2001; 154:106–14. https://doi.org/10.1093/aje/154.2.106 [PubMed]
- 10. Capasso M, Diskin SJ. Genetics and genomics of neuroblastoma. Cancer Treat Res. 2010; 155:65–84. https://doi.org/10.1007/978-1-4419-6033-7_4 [PubMed]
- 11. Capasso M, Diskin S, Cimmino F, Acierno G, Totaro F, Petrosino G, Pezone L, Diamond M, McDaniel L, Hakonarson H, Iolascon A, Devoto M, Maris JM. Common genetic variants in NEFL influence gene expression and neuroblastoma risk. Cancer Res. 2014; 74:6913–24. https://doi.org/10.1158/0008-5472.CAN-14-0431 [PubMed]
- 12. Han W, Zhou Y, Zhong R, Wu C, Song R, Liu L, Zou L, Qiao Y, Zhai K, Chang J, Huang L, Liu L, Lu X, et al. Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population. PLoS One. 2013; 8:e71656. https://doi.org/10.1371/journal.pone.0071656 [PubMed]
- 13. Jin Y, Wang H, Han W, Lu J, Chu P, Han S, Ni X, Ning B, Yu D, Guo Y. Single nucleotide polymorphism rs11669203 in TGFBR3L is associated with the risk of neuroblastoma in a Chinese population. Tumour Biol. 2016; 37:3739–47. https://doi.org/10.1007/s13277-015-4192-6 [PubMed]
- 14. He J, Wang F, Zhu J, Zhang R, Yang T, Zou Y, Xia H. Association of potentially functional variants in the XPG gene with neuroblastoma risk in a Chinese population. J Cell Mol Med. 2016; 20:1481–90. https://doi.org/10.1111/jcmm.12836 [PubMed]
- 15. Zheng J, Zhang R, Zhu J, Wang F, Yang T, He J, Xia H. Lack of Associations between XPC Gene Polymorphisms and Neuroblastoma Susceptibility in a Chinese Population. BioMed Res Int. 2016; 2016:2932049. https://doi.org/10.1155/2016/2932049 [PubMed]
- 16. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997; 88:323–31. https://doi.org/10.1016/S0092-8674(00)81871-1 [PubMed]
- 17. Sager R. Tumor suppressor genes: the puzzle and the promise. Science. 1989; 246:1406–12. https://doi.org/10.1126/science.2574499 [PubMed]
- 18. Xu H, el-Gewely MR. P53-responsive genes and the potential for cancer diagnostics and therapeutics development. Biotechnol Annu Rev. 2001; 7:131–64. https://doi.org/10.1016/S1387-2656(01)07035-1 [PubMed]
- 19. Vousden KH, Prives C. Blinded by the Light: The Growing Complexity of p53. Cell. 2009; 137:413–31. https://doi.org/10.1016/j.cell.2009.04.037 [PubMed]
- 20. Sharpless NE, DePinho RA. p53: good cop/bad cop. Cell. 2002; 110:9–12. https://doi.org/10.1016/S0092-8674(02)00818-8 [PubMed]
- 21. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000; 408:307–10. https://doi.org/10.1038/35042675 [PubMed]
- 22. Whibley C, Pharoah PD, Hollstein M. p53 polymorphisms: cancer implications. Nat Rev Cancer. 2009; 9:95–107. https://doi.org/10.1038/nrc2584 [PubMed]
- 23. Wang Y, Wu XS, He J, Ma T, Lei W, Shen ZY. A novel TP53 variant (rs78378222 A > C) in the polyadenylation signal is associated with increased cancer susceptibility: evidence from a meta-analysis. Oncotarget. 2016; 7:32854–65. [PubMed]
- 24. Børresen AL, Andersen TI, Garber J, Barbier-Piraux N, Thorlacius S, Eyfjörd J, Ottestad L, Smith-Sørensen B, Hovig E, Malkin D, et al. Screening for germ line TP53 mutations in breast cancer patients. Cancer Res. 1992; 52:3234–36. [PubMed]
- 25. Klug SJ, Ressing M, Koenig J, Abba MC, Agorastos T, Brenna SM, Ciotti M, Das BR, Del Mistro A, Dybikowska A, Giuliano AR, Gudleviciene Z, Gyllensten U, et al. TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol. 2009; 10:772–84. https://doi.org/10.1016/S1470-2045(09)70187-1 [PubMed]
- 26. Dahabreh IJ, Linardou H, Bouzika P, Varvarigou V, Murray S. TP53 Arg72Pro polymorphism and colorectal cancer risk: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010; 19:1840–47. https://doi.org/10.1158/1055-9965.EPI-10-0156 [PubMed]
- 27. Srivastava K, Srivastava A, Sharma KL, Mittal B. Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis. Mutat Res. 2011; 728:67–79. https://doi.org/10.1016/j.mrrev.2011.06.002 [PubMed]
- 28. Dahabreh IJ, Schmid CH, Lau J, Varvarigou V, Murray S, Trikalinos TA. Genotype misclassification in genetic association studies of the rs1042522 TP53 (Arg72Pro) polymorphism: a systematic review of studies of breast, lung, colorectal, ovarian, and endometrial cancer. Am J Epidemiol. 2013; 177:1317–25. https://doi.org/10.1093/aje/kws394 [PubMed]
- 29. Findlay JM, Middleton MR, Tomlinson I. A systematic review and meta-analysis of somatic and germline DNA sequence biomarkers of esophageal cancer survival, therapy response and stage. Ann Oncol. 2015; 26:624–44. https://doi.org/10.1093/annonc/mdu449 [PubMed]
- 30. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993; 11:1466–77. https://doi.org/10.1200/JCO.1993.11.8.1466 [PubMed]
- 31. Bullock AN, Fersht AR. Rescuing the function of mutant p53. Nat Rev Cancer. 2001; 1:68–76. https://doi.org/10.1038/35094077 [PubMed]
- 32. Tan H, Bao J, Zhou X. Genome-wide mutational spectra analysis reveals significant cancer-specific heterogeneity. Sci Rep. 2015; 5:12566. https://doi.org/10.1038/srep12566 [PubMed]
- 33. Matlashewski GJ, Tuck S, Pim D, Lamb P, Schneider J, Crawford LV. Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol. 1987; 7:961–63. https://doi.org/10.1128/MCB.7.2.961 [PubMed]
- 34. Boltze C, Roessner A, Landt O, Szibor R, Peters B, Schneider-Stock R. Homozygous proline at codon 72 of p53 as a potential risk factor favoring the development of undifferentiated thyroid carcinoma. Int J Oncol. 2002; 21:1151–54. [PubMed]
- 35. Pietsch EC, Humbey O, Murphy ME. Polymorphisms in the p53 pathway. Oncogene. 2006; 25:1602–11. https://doi.org/10.1038/sj.onc.1209367 [PubMed]
- 36. Hrstka R, Coates PJ, Vojtesek B. Polymorphisms in p53 and the p53 pathway: roles in cancer susceptibility and response to treatment. J Cell Mol Med. 2009; 13:440–53. https://doi.org/10.1111/j.1582-4934.2008.00634.x [PubMed]
-
37.
Dumont P, Leu JI, Della Pietra AC
3rd , George DL, Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003; 33:357–65. https://doi.org/10.1038/ng1093 [PubMed] - 38. Pim D, Banks L. p53 polymorphic variants at codon 72 exert different effects on cell cycle progression. Int J Cancer. 2004; 108:196–99. https://doi.org/10.1002/ijc.11548 [PubMed]
- 39. Khan MS, Pandith AA, Masoodi SR, Khan SH, Rather TA, Andrabi KI, Mudassar S. Significant association of TP53 Arg72Pro polymorphism in susceptibility to differentiated thyroid cancer. Cancer Biomark. 2015; 15:459–65. https://doi.org/10.3233/CBM-150485 [PubMed]
- 40. Chowdhury MK, Moniruzzaman M, Emran AA, Mostafa MG, Kuddus RH, Uddin MA. TP53 Codon 72 Polymorphisms and Lung Cancer Risk in the Bangladeshi Population. Asian Pac J Cancer Prev. 2015; 16:3493–98. https://doi.org/10.7314/APJCP.2015.16.8.3493 [PubMed]
- 41. Wu GC, Zhang ZT. Genetic association of single nucleotide polymorphisms in P53 pathway with gastric cancer risk in a Chinese Han population. Med Oncol. 2015; 32:401. https://doi.org/10.1007/s12032-014-0401-1 [PubMed]
- 42. Chen R, Liu S, Ye H, Li J, Du Y, Chen L, Liu X, Ding Y, Li Q, Mao Y, Ai S, Zhang P, Ma W, Yang H. Association of p53 rs1042522, MDM2 rs2279744, and p21 rs1801270 polymorphisms with retinoblastoma risk and invasion in a Chinese population. Sci Rep. 2015; 5:13300. https://doi.org/10.1038/srep13300 [PubMed]
- 43. Cattelani S, Ferrari-Amorotti G, Galavotti S, Defferrari R, Tanno B, Cialfi S, Vergalli J, Fragliasso V, Guerzoni C, Manzotti G, Soliera AR, Menin C, Bertorelle R, et al. The p53 codon 72 Pro/Pro genotype identifies poor-prognosis neuroblastoma patients: correlation with reduced apoptosis and enhanced senescence by the p53-72P isoform. Neoplasia. 2012; 14:634–43. https://doi.org/10.1593/neo.12594 [PubMed]
- 44. Diskin SJ, Capasso M, Diamond M, Oldridge DA, Conkrite K, Bosse KR, Russell MR, Iolascon A, Hakonarson H, Devoto M, Maris JM. Rare variants in TP53 and susceptibility to neuroblastoma. J Natl Cancer Inst. 2014; 106:dju047. https://doi.org/10.1093/jnci/dju047 [PubMed]
- 45. Rihani A, De Wilde B, Zeka F, Laureys G, Francotte N, Tonini GP, Coco S, Versteeg R, Noguera R, Schulte JH, Eggert A, Stallings RL, Speleman F, et al. CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients. PLoS One. 2014; 9:e114696. https://doi.org/10.1371/journal.pone.0114696 [PubMed]
- 46. Stoll C, Baretton G, Löhrs U. The influence of p53 and associated factors on the outcome of patients with oral squamous cell carcinoma. Virchows Arch. 1998; 433:427–33. https://doi.org/10.1007/s004280050270 [PubMed]
- 47. Tan H, Bao J, Zhou X. A novel missense-mutation-related feature extraction scheme for ‘driver’ mutation identification. Bioinformatics. 2012; 28:2948–55. https://doi.org/10.1093/bioinformatics/bts558 [PubMed]
- 48. He J, Zhang R, Zou Y, Zhu J, Yang T, Wang F, Xia H. Evaluation of GWAS-identified SNPs at 6p22 with neuroblastoma susceptibility in a Chinese population. Tumour Biol. 2016; 37:1635–39. https://doi.org/10.1007/s13277-015-3936-7 [PubMed]
- 49. He J, Yang T, Zhang R, Zhu J, Wang F, Zou Y, Xia H. Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children. J Cell Mol Med. 2016; 20:1534–41. https://doi.org/10.1111/jcmm.12846 [PubMed]
- 50. He J, Zhong W, Zeng J, Zhu J, Zhang R, Wang F, Yang T, Zou Y, Xia H. LMO1 gene polymorphisms contribute to decreased neuroblastoma susceptibility in a Southern Chinese population. Oncotarget. 2016; 7:22770–78. [PubMed]
- 51. He J, Qiu LX, Wang MY, Hua RX, Zhang RX, Yu HP, Wang YN, Sun MH, Zhou XY, Yang YJ, Wang JC, Jin L, Wei QY, Li J. Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations. Hum Genet. 2012; 131:1235–44. https://doi.org/10.1007/s00439-012-1152-8 [PubMed]
- 52. Fu W, Zhu J, Xiong SW, Jia W, Zhao Z, Zhu SB, Hu JH, Wang FH, Xia H, He J, Liu GC. BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility. EBioMedicine. 2017; 16:101–05. https://doi.org/10.1016/j.ebiom.2017.01.038 [PubMed]
- 53. Hua RX, Zhuo ZJ, Zhu J, Jiang DH, Xue WQ, Zhang SD, Zhang JB, Li XZ, Zhang PF, Jia WH, Shen GP, He J. Association between genetic variants in the XPG gene and gastric cancer risk in a Southern Chinese population. Aging (Albany NY). 2016; 8:3311–20. https://doi.org/10.18632/aging.101119 [PubMed]