PIK3CA Somatic Mutation Status in Relation to Patient and Tumor Factors in Racial/Ethnic Minorities with Colorectal Cancer

Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1046-51. doi: 10.1158/1055-9965.EPI-15-0204. Epub 2015 May 20.

Abstract

Background: Approximately 10% to 20% of colorectal cancers exhibit somatic mutations in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene (PIK3CA). We evaluated the relationship of PIK3CA mutation status in colorectal cancer with race/ethnicity, colorectal cancer survival, and other patient and tumor factors.

Methods: This study comprised 377 racial/ethnic minorities with incident invasive colorectal cancer, enrolled in the Colon Cancer Family Registry via population-based cancer registries. Tumor specimens were tested for PIK3CA mutations in exon 9 and 20 hotspots, BRAF p.V600E mutations, and DNA mismatch repair (MMR). In logistic regression models, we evaluated the association between PIK3CA mutation status and race/ethnicity, overall, and by mutation site. Using Cox regression, we evaluated the association between PIK3CA mutation status and survival after colorectal cancer diagnosis.

Results: PIK3CA mutations were detected in 42 cases (11%), with a similar prevalence across racial/ethnic groups. Individuals with PIK3CA-mutated colorectal cancer were significantly more likely than those with PIK3CA-wildtype disease to have proximal colon cancer, MMR-deficient tumors, and a germline MMR mutation (P ≤ 0.01). There was no evidence for an association between PIK3CA and overall survival (HR, 0.77; 95% confidence interval, 0.43-1.39).

Conclusions: The prevalence of PIK3CA mutation status in colorectal cancer does not differ according to race/ethnicity, but may vary according to other relevant clinicopathologic and etiologic factors, including germline MMR mutation status, tumor MMR status, and tumor site.

Impact: These findings underscore the importance of PIK3CA mutation status in colorectal cancer epidemiology and provide evidence that the prevalence of such mutations is similar across several racial/ethnic groups.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Class I Phosphatidylinositol 3-Kinases
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics*
  • Female
  • Global Health
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Minority Groups*
  • Mutation*
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • SEER Program
  • United States / epidemiology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human