Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk.
OBJECTIVE
The phosphatidylinositol 3-kinase signaling pathway is frequently activated in cancer. Emerging evidence supports the p85alpha regulatory subunit gene, PIK3R1, as a novel oncogene.


METHODS
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.
Li
Li
L
Department of Family Medicine-Research Division, Case Western Reserve University, Cleveland, OH 44106-7136, USA. lxl162@cwru.edu
Plummer
Sarah J
SJ
Thompson
Cheryl L
CL
Tucker
Thomas C
TC
Casey
Graham
G
D019943:Amino Acid Substitution; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors
D019869:Phosphatidylinositol 3-Kinases