Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer

Melissa Kang, Xiang J. Shen, Sangmi Kim, Felix Araujo-Perez, Joseph A. Galanko, Chris F. Martin, Robert S. Sandler, Temitope O. Keku

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

BACKGROUND AND 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.

Original languageEnglish (US)
Pages (from-to)359-366
Number of pages8
JournalCancer Biomarkers
Volume13
Issue number5
DOIs
StatePublished - Dec 1 2013

Fingerprint

African Americans
Colorectal Neoplasms
Confidence Intervals
Mutation
Genes
Odds Ratio
Microsatellite Instability
Logistic Models
Proportional Hazards Models
Neoplasms
Education
Polymerase Chain Reaction
Mortality
DNA

Keywords

  • African-Americans
  • BRAF
  • Colorectal cancer
  • KRAS
  • PIK3CA

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Kang, M., Shen, X. J., Kim, S., Araujo-Perez, F., Galanko, J. A., Martin, C. F., ... Keku, T. O. (2013). Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer. Cancer Biomarkers, 13(5), 359-366. https://doi.org/10.3233/CBM-130366

Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer. / Kang, Melissa; Shen, Xiang J.; Kim, Sangmi; Araujo-Perez, Felix; Galanko, Joseph A.; Martin, Chris F.; Sandler, Robert S.; Keku, Temitope O.

In: Cancer Biomarkers, Vol. 13, No. 5, 01.12.2013, p. 359-366.

Research output: Contribution to journalArticle

Kang, M, Shen, XJ, Kim, S, Araujo-Perez, F, Galanko, JA, Martin, CF, Sandler, RS & Keku, TO 2013, 'Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer', Cancer Biomarkers, vol. 13, no. 5, pp. 359-366. https://doi.org/10.3233/CBM-130366
Kang M, Shen XJ, Kim S, Araujo-Perez F, Galanko JA, Martin CF et al. Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer. Cancer Biomarkers. 2013 Dec 1;13(5):359-366. https://doi.org/10.3233/CBM-130366
Kang, Melissa ; Shen, Xiang J. ; Kim, Sangmi ; Araujo-Perez, Felix ; Galanko, Joseph A. ; Martin, Chris F. ; Sandler, Robert S. ; Keku, Temitope O. / Somatic gene mutations in African Americans may predict worse outcomes in colorectal cancer. In: Cancer Biomarkers. 2013 ; Vol. 13, No. 5. pp. 359-366.
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abstract = "BACKGROUND AND 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.",
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AU - Martin, Chris F.

AU - Sandler, Robert S.

AU - Keku, Temitope O.

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N2 - BACKGROUND AND 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.

AB - BACKGROUND AND 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.

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