Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer.
OBJECTIVE
African Americans have worse outcomes in colorectal cancer (CRC) than Caucasians. We sought to determine if KRAS, BRAF and PIK3CA mutations might contribute to the racial differences in CRC outcome.


METHODS
DNA was extracted from tissue microarrays made from CRC samples from 67 African Americans and 237 Caucasians. Mutations in KRAS, BRAF, and PIK3CA were evaluated by PCR sequencing. We also examined microsatellite instability (MSI) status. Associations of mutation status with tumor stage and grade were examined using a logistic regression model. Cox proportional hazards models were used to estimate the all-cause mortality associated with mutational status, race and other clinicopathologic features.


RESULTS
KRAS mutations were more common in African Americans than among Caucasians (37% vs 21%, p=0.01) and were associated with advanced stage (unadjusted odds ratio (OR)=3.31, 95% confidence interval (CI) 1.03-10.61) and grade (unadjusted OR=5.60, 95% CI 1.01-31.95) among African Americans. Presence of BRAF mutations was also positively associated with advanced tumor stage (adjusted OR=3.99, 95%CI 1.43-11.12) and grade (adjusted OR=3.93, 95%CI 1.05-14.69). PIK3CA mutations showed a trend toward an association with an increased risk of death compared to absence of those mutations (adjusted for age, sex and CRC site HR=1.89, 95% CI 0.98-3.65). Among African Americans, the association was more evident (adjusted for age, sex and CRC site HR=3.92, 95% CI 1.03-14.93) and remained significant after adjustment for MSI-H status and combined education-income level, with HR of 12.22 (95%CI 1.32-121.38).


CONCLUSIONS
Our results suggest that African Americans may have different frequencies of somatic genetic alterations that may partially explain the worse prognosis among African Americans with CRC compared to whites.
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Melissa
M
Kang
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Xiang J
XJ
Shen
Georgia Regents University Cancer Center, Section of Hematology/Oncology, Department of Medicine, Medical College of Georgia, Augusta, GA, USA.
Sangmi
S
Kim
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Felix
F
Araujo-Perez
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Joseph A
JA
Galanko
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Chris F
CF
Martin
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Robert S
RS
Sandler
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Temitope O
TO
Keku
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012306:Risk; D046888:Tissue Array Analysis; D044465:White People; D018631:ras Proteins / Q000235:genetics*
D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C482119:BRAF protein, human
African-Americans; BRAF; KRAS; PIK3CA; colorectal cancer