alexa Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk.


Journal of Integrative Oncology

Author(s): Li L, Plummer SJ, Thompson CL, Tucker TC, Casey G

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Abstract PURPOSE: The phosphatidylinositol 3-kinase signaling pathway is frequently activated in cancer. Emerging evidence supports the p85alpha regulatory subunit gene, PIK3R1, as a novel oncogene. EXPERIMENTAL DESIGN: We examined the association of a functional missense polymorphism (Met326Ile) of PIK3R1 with colon cancer risk in a population-based case-control study of 421 incident cases and 483 controls. RESULTS: In our base unconditional logistic regression model controlling for age, gender, and race, we observed a 47\% increase in risk among those carrying one or two copies of the 326Ile variant (P = 0.01). Further adjustment for family history of colorectal cancer, body mass index, nonsteroidal anti-inflammatory drugs, smoking, alcohol consumption, and physical activity strengthened the association [odds ratio (OR), 1.73; 95\% confidence interval (CI), 1.24-2.42, P = 0.001]. The association was more pronounced among those older than 64 years (OR, 2.10; 95\% CI, 1.19-3.70, P = 0.01). Evaluation of the genotypes assuming an additive mode of inheritance showed a significant trend for gene-dose response, where compared with Met/Met, the OR estimates for Ile/Met and Ile/Ile were 1.68 (95\% CI, 1.19-2.37) and 2.27 (95\% CI, 0.98-5.29), respectively (P for trend = 0.001). CONCLUSIONS: This study is the first to describe a significant association between a germ line functional variant in PIK3R1 and cancer, providing new evidence supporting a role for PIK3R1 in the development of colon cancer. This article was published in Clin Cancer Res and referenced in Journal of Integrative Oncology

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