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

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.