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.
Highlights
Members of the inositol phosphate metabolism pathway regulate cell proliferation, migration and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and are frequently dysregulated in cancer
Our results showed that single nucleotide polymorphisms (SNPs) in this pathway have not reached genome-wide significance except SNP of PLCE1 for ESCC/GC, which was consistent with the original genome-wide association studies (GWAS) for each study
For ESCC, seven SNPs in PLCE1 were significantly related with ESCC risk, exceeding the Bonferroni-corrected threshold, which was previously identified by the initial GWAS; and a further five SNPs in INPP4B and INPP5A with P, 0.001 (Supplementary Table SI)
Summary
Members of the inositol phosphate metabolism pathway regulate cell proliferation, migration and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and are frequently dysregulated in cancer. Members of the inositol phosphate metabolism pathway contain inositol and its associated factors, such as inositol phosphates, phosphoinositides (PI), the enzymes they need for synthesis and transformation, and so on They play crucial roles in normal physiological conditions, such as insulin signaling, PI3K/Akt signaling, endocytosis, vesicle trafficking, cell migration, proliferation, apoptosis and maintaining the state of homeostasis for many second messages[8]. We evaluated associations between inositol phosphate metabolism genes and the risk of eight different types of cancer (lung cancer, bladder cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), prostate cancer, breast cancer, renal www.nature.com/scientificreports cell carcinoma (RCC) and pancreatic cancer), using a comprehensive pathway-based analysis of the first phase of GWAS available in dbGAP database(www.ncbi.nlm.nih.gov/gap). Our results suggested that the overall inositol phosphate metabolism pathway may be associated with four different types of cancer development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
