Purpose: Approximately 10-30 % of colorectal cancers exhibit somatic mutations in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene (PIK3CA). We evaluated the relationship between PIK3CA mutation status and demographic factors, lifestyle factors, and other tumor characteristics and the relationship between PIK3CA mutation status and colorectal cancer survival.
Methods: The population-based study included postmenopausal women with invasive colorectal cancer diagnosed between 1998 and 2002 in Western Washington State. Participants were interviewed, and tumor specimens were tested for PIK3CA mutations in exons 9 and 20 hotspots, KRAS exon 2 mutations, BRAF p.V600E mutation, and microsatellite instability. We used Cox regression to evaluate the association between PIK3CA mutation status and disease-specific and overall survival. Stratified analyses were conducted by KRAS mutation status.
Results: PIK3CA mutations were evident in approximately 13 % of cases (N = 35). Women with PIK3CA-mutated colorectal cancer were significantly more likely than those with PIK3CA wild-type disease to be non-white, to have proximal colon cancer, and to have KRAS-mutated tumors (p < 0.05). In Cox proportional hazards regression analyses, overall survival was poorer, although not statistically significantly so, for women with PIK3CA-mutated versus wild-type colorectal cancer (hazard ratio = 1.74, 95 % confidence interval 0.86-3.50). This association between PIK3CA mutation status and survival was evident only when analyses were restricted to cases without somatic KRAS mutations (hazard ratio = 2.94, 95 % confidence interval 1.12-7.73).
Conclusions: PIK3CA-mutated colorectal cancer appears to have a distinct epidemiologic profile that is of clinical significance. Women with PIK3CA-mutated colorectal cancer experience a poorer prognosis than those with PIK3CA wild-type disease.