Abstract C111: Differential somatic allelic loss of chromosome 9p21-24 among Black and White colon cancers

Abstract Background. Disparities in the incidence and overall survival (OS) from colon cancer (CC) between Black Americans (BA) and White Americans (WA) can be mitigated through navigated screening, improving outcomes for both races. The disparity exists from a variety of factors with the largest contribution from the economics associated with birth zip code. Subsequent biological consequences over a life’s period include alterations in gut microbiome and inflammation among other insults, setting up colonic stems cells to acquire somatic genetic changes that propel earlier and potentially more aggressive cancers. We have previously demonstrated elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is associated with poor OS, with loss of heterozygosity (LOH) at the short arm of chromosome 9 (9p-LOH) improving OS of CC patients exhibiting EMAST. Here we examined for differences by race for 9p-LOH +/- EMAST. Materials & Methods. One hundred thirty-six cases (68 WA cases and 68 BA cases) in the North Carolina Colon Cancer Study I cohort were examined for 9p-LOH plus EMAST. Among them, 46 WA/BA pairs matched for factors associated with OS - including sex, tumor stage, tumor location and smoking habits - were selected and analyzed for possible associations between race and 9p-LOH, EMAST and 9p-LOH plus EMAST. 9p-LOH was determined at 7 single nucleotide polymorphism (SNP) loci present on the 9p21-24 region by digital PCR. EMAST was determined at 14 markers including 2 markers with mono-nucleotide repeats, 5 markers with di-nucleotide repeats, and 7 tetranucleotide markers by fragment analysis. Results. The 5-yr OS rate of WA CC was higher than BA CC in univariate (HR:1.98, 95%CI: 0.97-4.03, p=0.058) and multivariate (HR:2.8, 95%CI: 1.12-6.6, p=0.018) COX proportional Hazard test. 9p-LOH was found in 15.2% (7/46 cases) of BA CC versus 54.3% of WA CC (25/46 cases) (OR: 0.35,95%CI: 0.13-0.97, p=0.04 through univariate, and OR:0.29, 95%CI: 0.095-0.86, p=0.026 through multivariate logistic regression tests adjusted for age, sex, tumor stage, tumor location and smoking status). EMAST was found in 43.4% (20/46 cases) of BA CC and 41.3% (19/46 cases) of WA CC. 9p-LOH plus EMAST was found in 8.7% (4/46 cases) of BA CC and 15.2% (7/46 cases) of WA CC. There was no significant association between 9p-LOH plus EMAST and WA CC (p=0.10). 9p-LOH was not associated with 5-yr OS (p=0.75 by univariate COX proportional hazard test). Conclusions. We show that 9p-LOH, EMAST, or 9p-LOH plus EMAST are not associated with OS of WA/BA CC patients. However, the incidence of 9p-LOH is significantly higher in WA CC than BA CC, suggesting that the environment influence on somatic genetic changes within CC may be different between WA and BA patients. Citation Format: Minoru Koi, Yuki Aisu, Susan Ahmedyar, John M. Carethers. Differential somatic allelic loss of chromosome 9p21-24 among Black and White colon cancers [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C111.