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Sci Rep. 2015 Feb 16;5:8473. doi: 10.1038/srep08473.

Genetic variants in the inositol phosphate metabolism pathway and risk of different types of cancer.

Author information

1
State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institution of Digestive Disease, 145 Middle Shandong Rd, Shanghai 200001, China.
2
Department of Otolaryngology, The Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai 200233, China.

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.

PMID:
25683757
PMCID:
PMC4329558
DOI:
10.1038/srep08473
[Indexed for MEDLINE]
Free PMC Article

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