title: Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.
abstract: Distant metastasis is the primary failure pattern of nasopharyngeal carcinoma(NPC) in intensity-modulated radiation therapy(IMRT) era. This study was conducted to find the impact of genetic variations in the phosphatidylinositol 3-kinase(PI3K)/phosphatase and tensin homologue(PTEN)/v-akt murine thymoma viral oncogene homologue(AKT)/mammalian target of rapamycin(mTOR) pathway on the risk of distant metastasis in NPC. We genotyped 16 single-nucleotide polymorphisms(SNPs) in five core genes in this pathway from 496 patients treated by IMRT with or without chemotherapy. The relationships between genetic polymorphisms and distant progression were evaluated. We observed that two loci in the AKT1 gene(rs3803300 and rs2494738 alone or combined) were associated with prognosis, with patients carrying at least one variant allele had significantly reduced risk of distant failure, especially in N2-3 group. In addition, we found that genetic variation may had some joint effect with N classification in recursive-partitioning analysis(RPA) analysis, with which patients were stratified into four different risk subgroups (RPA model): RPA1(low risk), RPA2(moderate risk), RPA3(high risk) and RPA4(highest risk). Our findings suggested that genetic variations within the PI3K signaling pathway modulate the development and invasion of NPC patients. Further research is needed to replicate the study in other centers and races, and to unravel the functional significance of these polymorphisms.
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.
authors.forename: Qiaojuan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Lu
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Clinical Laboratory, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Radiation Biology Laboratory, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Clinical Laboratory, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Radiation Biology Laboratory, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Radiation Biology Laboratory, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, 350014, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Lin
authors.affiliation: Shengli Clinical Medicine College, Fujian Medical University, Fuzhou, Fujian Province, 350014, China.|Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, 350014, China.
authors.forename: Jianji
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D050397:Radiotherapy, Intensity-Modulated; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases