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Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers
Zhenghe Wang1, Li Li1, Kishore Guda1
1Department of Genetics and Genome Sciences (ZW), Department of Family Medicine (LL, ZC), Division of Hematology and Oncology, Department of Medicine (SDM), Department of Epidemiology and Biostatistics (JBS), Department of Pathology (JW), Case Comprehensive Cancer Center (ZW, LL, KG, JBS, YSP, SDM, JW), Case Western Reserve University and Case Medical Center (LL, SDM, JW), Cleveland, OH.
Abstract:
African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) developed metastatic disease vs only four of 39 mutation-negative (Mut-) cases (P = .03, Cox regression model with two-sided Wald test). Moreover, among stage III cases (n = 33), Mut+ cancers were nearly three times more likely to relapse as Mut- cases (7 of 15 Mut+ vs 3 of 18 Mut-; P = .03, Cox regression model with two-sided Wald test). AA-CRC mutations may thus define a high-risk subset of CRCs that contributes to the overall disparity in CRC outcomes observed in African Americans.
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