Since multistage carcinogenesis is frequently associated with the loss of suppressor gene activity, and since in over 90% of cases of nasopharyngeal carcinoma (NPC) p53 alterations are not involved [Sun, Y., Hegamyer, G.H., Cheng, Y.-J., Hildesheim, A., Chen, J.-Y., Chen, I.-H., Cao, Y., Yao, K.-T. & Colburn, N.H. (1992).Proc.Natl.Acad.Sci.
Whilst more detailed genetic analysis is required, our results suggest that mechanisms other than mutation of the p53 gene may be responsible for the stabilization of the protein in cases of undifferentiated NPC.
The DeltaNp63 has been postulated to have a dominant-negative effect on the function of the p53 gene and may play a role in the pathogenesis of nasopharyngeal carcinoma.
Three p53 DNA polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a 16-bp duplication in intron 3) and their haplotype combinations were studied in 73 patients (61 males and 12 females) with nasopharyngeal cancer and 105 healthy controls from the Guizhou province in southern China.
Among the 15 SNPs detected in the meta-analysis, miR-146a (rs2910164, C>G), HCG9 (rs3869062, A>G), HCG9 (rs16896923, T>C), MMP2 (rs243865, C>T), GABBR1 (rs2076483, T>C), and TP53 (rs1042522, C>G) were associated with decreased susceptibility to NPC, while GSTM1 (+/DEL), IL-10 (rs1800896, A>G), MDM2 (rs2279744, T>G), MDS1-EVI1 (rs6774494, G>A), XPC (rs2228000, C>T), HLA-F (rs3129055, T>C), SPLUNC1 (rs2752903, T>C; and rs750064, A>G), and GABBR1 (rs29232, G>A) were associated with increased susceptibility to NPC.
These results indicate that the p53 mutations are an infrequent event in NPC in Spanish patients needing exogenous factors as the EBV infection for the development of this malignancy.
The results suggested that the Arg399Gln polymorphism of XRCC1 gene, the 1G/2G polymorphism of MMP-1 gene, the RsaI polymorphism of CYP2E1 gene, the -1306C>T polymorphism of MMP-2 gene and the Arg72Pro polymorphism of p53 gene might be related to increased risks of nasopharyngeal carcinoma under different genetic comparison models, while the Arg194Trp and Arg280His polymorphisms of XRCC1 gene and the 309T>G polymorphism of MDM2 gene might not contribute to the risk of nasopharyngeal carcinoma.
These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.
We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in less than 10% of NPC cases.
We have therefore studied 64 patients (54 males and 10 females) with nasopharyngeal carcinoma and 99 healthy controls from the Guizhou province in southern China with respect to association with the SspI polymorphism at the IFNA17 locus, and the possible interaction between IFNA17 and p53 alleles in the etiology of nasopharyngeal carcinoma.
These findings support the conclusion that the cell cycle regulation may play a role in nasopharyngeal carcinoma development and that CCND1A870G polymorphism maybe a useful biomarker for nasopharyngeal carcinoma progression.
For MMP2-1306 C>T polymorphism, significant associations were observed under three genetic models both in overall comparison and in a hospital-based subgroup, and in oral cavity cancer and nasopharyngeal cancer under dominant model as well.
Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 × 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 × 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 × 10(-8), P = 7.0 × 10(-7), and P = 8.4 × 10(-7), respectively; located in the CDKN2A/B gene region).
The methylation profile of NPC in order of frequency was CDH1 (50%), CDKN2B (50%), THBS1 (50%), RASSF1A (46%), MLH1 (40%), MGMT (28%), CDKN2A (23%), TP73 (20%), caspase-8 (7%), ARF (3%) and VHL (0%).
We found that NPC was associated with combined common and rare variants in <i>CDKN2A/2B</i> (<i>P</i> = 1.3 × 10<sup>-4</sup>), <i>BRD2</i> (<i>P</i> = 1.6 × 10<sup>-3</sup>), <i>TNFRSF19</i> (<i>P</i> = 4.0 × 10<sup>-3</sup>), and <i>CLPTM1L/TERT</i> (<i>P</i> = 5.4 × 10<sup>-3</sup>).
Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF-κB, and TGF-β pathways.
Our results provide molecular epidemiological evidence that the MMP2-1306C/T promoter polymorphism is associated with NPC risk, and this association is especially noteworthy in heavy smokers.
Nasopharyngeal carcinoma, which is very frequent in southern China, has in previous investigations been found to be associated with a number of risk factors, including a disease susceptibility gene linked to the HLA-region, p53 alleles and deletions of the chromosome 9p21-22 region, which includes the IFNA and p16 loci.
Nasopharyngeal carcinoma (NPC) is a platinum-sensitive cancer and excision repair cross-complementing group 1 (ERCC1) polymorphisms have been shown to predict survival in several cancers following platinum therapy.
Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.
The authors hypothesized that the ERCC1 genotype for the SNPs cytosine-to-thymine substitution at codon 118 (C118T) and cytosine-to-adenine substitution at codon 8092 (C8092A) is prognostic in patients with nasopharyngeal carcinoma (NPC) who receive either radiotherapy (RT) or cisplatin plus RT.