Genetic Variants in the Inositol Phosphate Metabolism Pathway and Risk of Different Types of Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2015 Feb 17

PMID 25683757

Citations 20

Authors

Juan Tan

Chen-Yang Yu

Zhen-Hua Wang

Hao-Yan Chen

Jian Guan

Ying-Xuan Chen

Jing-Yuan Fang

Affiliations

Soon will be listed here.

Abstract

Members of the inositol phosphate metabolism pathway regulate cell proliferation, migration and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and are frequently dysregulated in cancer. Whether germline genetic variants in inositol phosphate metabolism pathway are associated with cancer risk remains to be clarified. We examined the association between inositol phosphate metabolism pathway genes and risk of eight types of cancer using data from genome-wide association studies. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-based associations were tested using the permutation-based adaptive rank-truncated product method. The overall inositol phosphate metabolism pathway was significantly associated with risk of lung cancer (P = 2.00 × 10(-4)), esophageal squamous cell carcinoma (P = 5.70 × 10(-3)), gastric cancer (P = 3.03 × 10(-2)) and renal cell carcinoma (P = 1.26 × 10(-2)), but not with pancreatic cancer (P = 1.40 × 10(-1)), breast cancer (P = 3.03 × 10(-1)), prostate cancer (P = 4.51 × 10(-1)), and bladder cancer (P = 6.30 × 10(-1)). Our results provide a link between inherited variation in the overall inositol phosphate metabolism pathway and several individual genes and cancer. Further studies will be needed to validate these positive findings, and to explore its mechanisms.

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References

Ijuin T, Takenawa T . SKIP negatively regulates insulin-induced GLUT4 translocation and membrane ruffle formation. Mol Cell Biol. 2003; 23(4):1209-20. PMC: 141139. DOI: 10.1128/MCB.23.4.1209-1220.2003. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Bai Y, Edamatsu H, Maeda S, Saito H, Suzuki N, Satoh T . Crucial role of phospholipase Cepsilon in chemical carcinogen-induced skin tumor development. Cancer Res. 2004; 64(24):8808-10. DOI: 10.1158/0008-5472.CAN-04-3143. View

Maffucci T, Cooke F, Foster F, Traer C, Fry M, Falasca M . Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J Cell Biol. 2005; 169(5):789-99. PMC: 2171608. DOI: 10.1083/jcb.200408005. View

Bader A, Kang S, Zhao L, Vogt P . Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer. 2005; 5(12):921-9. DOI: 10.1038/nrc1753. View

Haiman C, Stram D, Cheng I, Giorgi E, Pooler L, Penney K . Common genetic variation at PTEN and risk of sporadic breast and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006; 15(5):1021-5. DOI: 10.1158/1055-9965.EPI-05-0896. View

Engelman J, Luo J, Cantley L . The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006; 7(8):606-19. DOI: 10.1038/nrg1879. View

Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38(8):904-9. DOI: 10.1038/ng1847. View

Katso R, Pardo O, Palamidessi A, Franz C, Marinov M, Laurentiis A . Phosphoinositide 3-Kinase C2beta regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms. Mol Biol Cell. 2006; 17(9):3729-44. PMC: 1593155. DOI: 10.1091/mbc.e05-11-1083. View

10.

Chiang K, Niessen S, Saghatelian A, Cravatt B . An enzyme that regulates ether lipid signaling pathways in cancer annotated by multidimensional profiling. Chem Biol. 2006; 13(10):1041-50. DOI: 10.1016/j.chembiol.2006.08.008. View

11.

Yeager M, Orr N, Hayes R, Jacobs K, Kraft P, Wacholder S . Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007; 39(5):645-9. DOI: 10.1038/ng2022. View

12.

Hunter D, Kraft P, Jacobs K, Cox D, Yeager M, Hankinson S . A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007; 39(7):870-4. PMC: 3493132. DOI: 10.1038/ng2075. View

13.

Vogt P, Kang S, Elsliger M, Gymnopoulos M . Cancer-specific mutations in phosphatidylinositol 3-kinase. Trends Biochem Sci. 2007; 32(7):342-9. DOI: 10.1016/j.tibs.2007.05.005. View

14.

Kim J, Lim S, Kim J, Kim S, Kim J, Ryu S . Subtype-specific roles of phospholipase C-β via differential interactions with PDZ domain proteins. Adv Enzyme Regul. 2010; 51(1):138-51. DOI: 10.1016/j.advenzreg.2010.10.004. View

15.

Danielsen S, Cekaite L, Agesen T, Sveen A, Nesbakken A, Thiis-Evensen E . Phospholipase C isozymes are deregulated in colorectal cancer--insights gained from gene set enrichment analysis of the transcriptome. PLoS One. 2011; 6(9):e24419. PMC: 3164721. DOI: 10.1371/journal.pone.0024419. View

16.

Menashe I, Figueroa J, Garcia-Closas M, Chatterjee N, Malats N, Picornell A . Large-scale pathway-based analysis of bladder cancer genome-wide association data from five studies of European background. PLoS One. 2012; 7(1):e29396. PMC: 3251580. DOI: 10.1371/journal.pone.0029396. View

17.

Li D, Duell E, Yu K, Risch H, Olson S, Kooperberg C . Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer. Carcinogenesis. 2012; 33(7):1384-90. PMC: 3405651. DOI: 10.1093/carcin/bgs151. View

18.

Ijuin T, Takenawa T . Regulation of insulin signaling by the phosphatidylinositol 3,4,5-triphosphate phosphatase SKIP through the scaffolding function of Pak1. Mol Cell Biol. 2012; 32(17):3570-84. PMC: 3422014. DOI: 10.1128/MCB.00636-12. View

19.

Li W, Hu N, Wang Z, Yu K, Su H, Wang L . Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population. PLoS One. 2013; 8(7):e68999. PMC: 3715462. DOI: 10.1371/journal.pone.0068999. View

20.

Karakas B, Colak D, Kaya N, Ghebeh H, Al-Qasem A, Hendrayani F . Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients. Cancer Biol Ther. 2013; 14(10):888-96. PMC: 3926885. DOI: 10.4161/cbt.25945. View