Abstract B40: Mutations in KRAS are increased in sporadic colon cancers of African Americans compared to Non-Hispanic Whites

Abstract

Abstract Introduction: African Americans (AA) have a higher incidence and mortality of colorectal cancer (CRC) when compared to Non-Hispanic Whites (NHW) and tumors present at later stages. Possible underlying factors include differences in diet, access to care and demographic differences, as well as variances in racial disease-specific gene mutations. Understanding mechanisms for this racial disparity is critical to delivery of better care. Several studies have investigated sporadic CRC mutational somatic differences between AAs and NHWs, but due to small study sizes and conflicting results, no definitive conclusions have been reached. Mutations in KRAS, BRAF, and PI3CA occur frequently in sporadic CRC and are associated with a worse prognosis. Therefore we investigated the frequency of these gene mutations in AA versus NHW populations as a possible causative factor in racial disparity of CRC. Here, we present the first systematic literature review and meta-analysis investigating the mutational differences in sporadic CRC between AAs and NHWs. Methods: We searched the PubMed database with a query designed to identify publications reporting mutations in KRAS, BRAF and PI3CA in CRC. Inclusion criteria were sporadic CRC, human subjects, English language, information on ethnicity (AA, NHW or both), total subject number >20, and information on KRAS, BRAF or PI3CA mutation frequencies. Each study was evaluated by two investigators to confirm presence of study criteria. Results: Our search identified 6162 publication. Twelve studies met the inclusion criteria, detected mutations in AAs and NHWs, and had extractable data. Ten studies reported on KRAS (n=4529), 6 studies on BRAF (n=2063), and 3 studies on PI3CA (n=662). We did not observe a statistically significant difference in the frequency of PI3CA (odds ratio 0.870 CI 0.559-1.36 p=0.5396) or BRAF mutations (odds ratio 1.24 CI 0.689-2.25, p=0.4683) when comparing CRC in AAs versus NHWs. However, KRAS mutations were more frequent in CRC in AAs when compared to NHWs (odds ratio 0.634 CI 0.529 - 0.760, p=0.0001). Conclusion: Here, we report on the mutational patterns of KRAS, BRAF and PI3CA in sporadic CRC of AAs and NHWs in the first systematic meta-analysis on this topic of previously published data. For the first time, we identify an increase in KRAS mutations in sporadic CRC in AAs which may contribute to worse prognosis and increased mortality of CRC in AAs. Future studies investigating health care disparities in CRC in AAs should account for KRAS mutational frequency. Citation Format: Nancy L. Krett, Jonas Staudacher, Ahmer Khalid, Vadim Bul, Joseph Zeidan, Cemal Yazici, Barbara Jung. Mutations in KRAS are increased in sporadic colon cancers of African Americans compared to Non-Hispanic Whites. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B40.